npm - @sjcrh/proteinpaint-server - Versions diffs - 2.42.1-0 → 2.42.2 - Mend

@sjcrh/proteinpaint-server 2.42.1-0 → 2.42.2

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Files changed (4) hide show

package/server.js CHANGED Viewed

@@ -1,2 +1,2 @@
-(()=>{var t={5037:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>c});var r=n(9157),s=n(1017),o=n.n(s),i=n(334),a=n.n(i),l=n(3345);const c={endpoint:"burden",methods:{get:{init:({genomes:t})=>async(e,n)=>{try{const s=t[e.query.genome];if(!s)throw`invalid q.genome=${e.query.genome}`;const i=e.query,c=s.datasets[i.dslabel];if(!c)throw`invalid q.genome=${e.query.dslabel}`;if(!c.cohort.cumburden?.files)throw"missing ds.cohort.cumburden.files";const f=await async function(t,e){const n=o().join(a().cachedir,Math.random().toString()+".json");for(const e in t.query)t.query[e]=Number(t.query[e]);const s=Object.assign({},u,t.query);await(0,l.Sf)(n,JSON.stringify(s));const{fit:i,surv:c,sample:f}=e.cohort.cumburden.files;if(!i||!c||!f)throw"missing one or more of ds.cohort.burden.files.{fit, surv, sample}";const d=[n,`${a().tpmasterdir}/${i}`,`${a().tpmasterdir}/${c}`,`${a().tpmasterdir}/${f}`],h=await(0,r.default)(o().join(a().binpath,"utils/burden.R"),[],d),p=JSON.parse(h[0]);return p}(e,c),{keys:d,rows:h}=function(t){const e=Object.keys(t[0]),n=[],r=[];for(const t of e)if("chc"==t)r.push(t),n.push(t);else{const e=Number(t.slice(1).split(",")[0]);e<=60&&e%2==0&&(r.push(t),n.push(`burden${e}`))}const s=[];for(const e of t)s.push(r.map((t=>e[t])));return{keys:n,rows:s}}(f);n.send({status:"ok",keys:d,rows:h})}catch(t){n.send({status:"error",error:t.message||t})}},request:{typeId:"BurdenRequest"},response:{typeId:"BurdenResponse"},examples:[{request:{body:{genome:"hg38",dslabel:"SJLife",diaggrp:5,sex:1,white:1,agedx:1,bleo:0,etop:0,cisp:0,carbo:0,steriod:0,vcr:0,hdmtx:0,itmt:0,ced:0,dox:0,heart:0,brain:0,abd:0,pelvis:0,chest:0}},response:{header:{status:200}}}]}}};const u=Object.freeze({diaggrp:5,sex:0,white:1,agedx:1,steriod:0,bleo:0,vcr:0,etop:0,itmt:0,ced:0,cisp:0,dox:0,carbo:0,hdmtx:0,brain:0,chest:0,heart:0,pelvis:0,abd:0})},2538:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>f,maxTotalSizeCompressed:()=>u});var r=n(1017),s=n.n(r),o=n(6452),i=n.n(o),a=n(334);const l=1e3,c="Aliquot Ensemble Somatic Variant Merging and Masking",u=n.n(a)().features.gdcMafMaxFileSize||4e8,f={endpoint:"gdc/maf",methods:{all:{init:function({genomes:t}){return async(e,n)=>{try{const r=t.hg38;if(!r)throw"hg38 missing";const o=r.datasets.GDC;if(!o)throw"hg38 GDC missing";const a=await async function(t,e){const n={op:"and",content:[{op:"=",content:{field:"data_format",value:"MAF"}},{op:"=",content:{field:"experimental_strategy",value:t.experimentalStrategy}},{op:"=",content:{field:"analysis.workflow_type",value:c}},{op:"=",content:{field:"access",value:"open"}}]},r={op:"and",content:[]};t.filter0&&r.content.push(t.filter0);const{host:o,headers:a}=e.getHostHeaders(t),d={filters:n,case_filters:r,size:l,fields:["id","file_size","cases.project.project_id","cases.submitter_id","cases.samples.sample_type"].join(",")},h=await i().post(s().join(o.rest,"files"),{headers:a,body:JSON.stringify(d)});let p;try{p=JSON.parse(h.body)}catch(t){throw"invalid JSON from "+f.endpoint}if(!Number.isInteger(p.data?.pagination?.total))throw"re.data.pagination.total is not int";if(!Array.isArray(p.data?.hits))throw"re.data.hits[] not array";const m=[];for(const t of p.data.hits){const e=t.cases?.[0];if(!e)throw"h.cases[0] missing";const n={id:t.id,project_id:e.project.project_id,file_size:t.file_size};n.case_submitter_id=e.submitter_id,e.samples&&(n.sample_types=e.samples.map((t=>t.sample_type)).sort()),m.push(n)}return{files:m,filesTotal:p.data.pagination.total,maxTotalSizeCompressed:u}}(e.query,o);n.send(a)}catch(t){n.send({status:"error",error:t.message||t})}}},request:{typeId:"GdcMafRequest"},response:{typeId:"GdcMafResponse"},examples:[{request:{body:{experimentalStrategy:"WXS",embedder:"localhost"}},response:{header:{status:200}}}]}}}},86:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>f});var r=n(6452),s=n.n(r),o=n(1017),i=n.n(o),a=n(1271),l=n(334),c=n.n(l),u=n(2538);const f={endpoint:"gdc/mafBuild",methods:{all:{init:function({genomes:t}){return async(e,n)=>{try{const r=t.hg38;if(!r)throw"hg38 missing";const o=r.datasets.GDC;if(!o)throw"hg38 GDC missing";await async function(t,e,n){const r=Date.now(),{host:o,headers:l}=n.getHostHeaders(t),f=await async function(t,e,n){if(0==t.length)throw"fileIdLst[] not array or blank";const r={filters:{op:"in",content:{field:"file_id",value:t}},size:1e4,fields:"file_size"},o=await s().post(i().join(e.rest,"files"),{headers:n,body:JSON.stringify(r)});let a;try{a=JSON.parse(o.body)}catch(t){throw"invalid json from getFileLstUnderSizeLimit"}if(!Array.isArray(a.data?.hits))throw"re.data.hits[] not array";const l=[];let c=0;for(const t of a.data.hits){if(c>=u.maxTotalSizeCompressed)break;if(!t.id)throw".id missing";if(!Number.isInteger(t.file_size))throw".file_size not integer";c+=t.file_size,l.push(t.id)}if(0==l.length)throw"no file available";return l}(t.fileIdLst,o,l);c().debugmode&&console.log(`${f.length} out of ${t.fileIdLst.length} input MAF files accepted by size limit`,Date.now()-r);const d={fileIdLst:f,columns:t.columns,host:i().join(o.rest,"data")},h=(0,a.run_rust_stream)("gdcmaf",JSON.stringify(d));e.setHeader("Content-Type","application/octet-stream"),e.setHeader("Content-Disposition","attachment; filename=cohort.maf.gz"),h.pipe(e),h.on("end",(()=>{c().debugmode&&console.log("rust gdcmaf",Date.now()-r),e.end()})),h.on("error",(t=>{console.error(t),e.statusCode=500,e.end("Internal Server Error")}))}(e.query,n,o)}catch(t){t.stack&&console.log(t.stack),n.send({status:"error",error:t.message||t})}}},request:{typeId:"GdcMafBuildRequest"},response:{typeId:null}}}}},889:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>l});var r=n(2273),s=n(6452),o=n.n(s),i=n(334),a=n.n(i);const l={endpoint:"gdc/topMutatedGenes",methods:{all:{init:function({genomes:t}){return async(e,n)=>{const s=e.query,i=t.hg38;if(!i)throw"hg38 missing";const l=i.datasets.GDC;if(!l)throw"hg38 GDC missing";try{const t=await async function(t,e){let n,s;const{host:i,headers:l}=e.getHostHeaders(t);a().features?.geneExpHost?(n=c.query,s=c.getVariables(t)):(n=u.query,s=u.getVariables(t));const f=await o().post(i.graphql,{headers:l,body:JSON.stringify({query:n,variables:s})}),d=JSON.parse(f.body),h=[];for(const t of d.data.genesTableViewer.explore.genes.hits.edges){if("object"!=typeof t.node)throw"node missing from re.data.genesTableViewer.explore.genes.hits.edges[]";const e=[];Number.isInteger(t.node.case_cnv_gain?.hits?.total)&&t.node.case_cnv_gain.hits.total>0&&e.push({class:r.mclasscnvgain,count:t.node.case_cnv_gain.hits.total}),Number.isInteger(t.node.case_cnv_loss?.hits?.total)&&t.node.case_cnv_loss.hits.total>0&&e.push({class:r.mclasscnvloss,count:t.node.case_cnv_loss.hits.total}),Number.isInteger(t.node.ssm_case?.hits?.total)&&t.node.ssm_case.hits.total>0&&e.push({dt:r.dtsnvindel,count:t.node.ssm_case.hits.total}),h.push({gene:t.node.symbol,mutationStat:e})}return h}(s,l),e={genes:t};n.send(e)}catch(t){n.send({status:"error",error:t.message||t})}}},request:{typeId:"GdcTopMutatedGeneRequest"},response:{typeId:"GdcTopMutatedGeneResponse"}}}};const c={query:"\nquery GenesTable_relayQuery(\n  $genesTable_filters: FiltersArgument\n  $genesTable_size: Int\n  $genesTable_offset: Int\n  $score: String\n  $ssmCase: FiltersArgument\n  $geneCaseFilter: FiltersArgument\n  $ssmTested: FiltersArgument\n  $cnvTested: FiltersArgument\n  $cnvGainFilters: FiltersArgument\n  $cnvLossFilters: FiltersArgument\n) {\n  genesTableViewer: viewer {\n    explore {\n      cases {\n        hits(first: 0, filters: $ssmTested) {\n          total\n        }\n      }\n      filteredCases: cases {\n        hits(first: 0, filters: $geneCaseFilter) {\n          total\n        }\n      }\n      cnvCases: cases {\n        hits(first: 0, filters: $cnvTested) {\n          total\n        }\n      }\n      genes {\n        hits(first: $genesTable_size, offset: $genesTable_offset, filters: $genesTable_filters, score: $score) {\n          total\n          edges {\n            node {\n              id\n              numCases: score\n              symbol\n              name\n              cytoband\n              biotype\n              gene_id\n              is_cancer_gene_census\n              ssm_case: case {\n                hits(first: 0, filters: $ssmCase) {\n                  total\n                }\n              }\n              cnv_case: case {\n                hits(first: 0, filters: $cnvTested) {\n                  total\n                }\n              }\n              case_cnv_gain: case {\n                hits(first: 0, filters: $cnvGainFilters) {\n                  total\n                }\n              }\n              case_cnv_loss: case {\n                hits(first: 0, filters: $cnvLossFilters) {\n                  total\n                }\n              }\n            }\n          }\n        }\n      }\n    }\n  }\n}\n",getVariables:t=>{const e={genesTable_filters:{op:"and",content:[]},genesTable_size:t.maxGenes||50,genesTable_offset:0,score:"case.project.project_id",ssmCase:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}},{op:"NOT",content:{field:"genes.case.ssm.observation.observation_id",value:"MISSING"}}]},geneCaseFilter:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},ssmTested:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},cnvTested:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"}]},cnvGainFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Gain"]},op:"in"}]},cnvLossFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Loss"]},op:"in"}]}};return t.filter0&&(e.genesTable_filters.content.push(JSON.parse(JSON.stringify(t.filter0))),e.geneCaseFilter.content.push(JSON.parse(JSON.stringify(t.filter0))),e.cnvTested.content.push(JSON.parse(JSON.stringify(t.filter0))),e.cnvGainFilters.content.push(JSON.parse(JSON.stringify(t.filter0))),e.cnvLossFilters.content.push(JSON.parse(JSON.stringify(t.filter0)))),"CGC"==t.geneFilter&&(e.genesTable_filters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),e.geneCaseFilter.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),e.cnvTested.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),e.cnvGainFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),e.cnvLossFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"})),e}},u={query:"\n          query GenesTable(\n            $caseFilters: FiltersArgument\n            $genesTable_filters: FiltersArgument\n            $genesTable_size: Int\n            $genesTable_offset: Int\n            $score: String\n            $ssmCase: FiltersArgument\n            $geneCaseFilter: FiltersArgument\n            $ssmTested: FiltersArgument\n            $cnvTested: FiltersArgument\n            $cnvGainFilters: FiltersArgument\n            $cnvLossFilters: FiltersArgument\n            $sort: [Sort]\n          ) {\n            genesTableViewer: viewer {\n              explore {\n                cases {\n                  hits(first: 0, case_filters: $ssmTested) {\n                    total\n                  }\n                }\n                filteredCases: cases {\n                  hits(first: 0, case_filters: $geneCaseFilter) {\n                    total\n                  }\n                }\n                cnvCases: cases {\n                  hits(first: 0, case_filters: $cnvTested) {\n                    total\n                  }\n                }\n                genes {\n                  hits(\n                    first: $genesTable_size\n                    offset: $genesTable_offset\n                    filters: $genesTable_filters\n                    case_filters: $caseFilters\n                    score: $score\n                    sort: $sort\n                  ) {\n                    total\n                    edges {\n                      node {\n                        id\n                        numCases: score\n                        symbol\n                        name\n                        cytoband\n                        biotype\n                        gene_id\n                        is_cancer_gene_census\n                        ssm_case: case {\n                          hits(first: 0, filters: $ssmCase) {\n                            total\n                          }\n                        }\n                        cnv_case: case {\n                          hits(first: 0, filters: $cnvTested) {\n                            total\n                          }\n                        }\n                        case_cnv_gain: case {\n                          hits(first: 0, filters: $cnvGainFilters) {\n                            total\n                          }\n                        }\n                        case_cnv_loss: case {\n                          hits(first: 0, filters: $cnvLossFilters) {\n                            total\n                          }\n                        }\n                      }\n                    }\n                  }\n                }\n              }\n            }\n          }",getVariables:t=>{const e={caseFilters:{op:"and",content:[]},genesTable_filters:{op:"and",content:[]},genesTable_size:t.maxGenes||50,genesTable_offset:0,score:"case.project.project_id",ssmCase:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}},{op:"NOT",content:{field:"genes.case.ssm.observation.observation_id",value:"MISSING"}}]},geneCaseFilter:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},ssmTested:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},cnvTested:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"}]},cnvGainFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Gain"]},op:"in"}]},cnvLossFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Loss"]},op:"in"}]}};return t.filter0&&(e.caseFilters.content.push(JSON.parse(JSON.stringify(t.filter0))),e.geneCaseFilter.content.push(JSON.parse(JSON.stringify(t.filter0))),e.cnvLossFilters.content.push(JSON.parse(JSON.stringify(t.filter0))),e.cnvGainFilters.content.push(JSON.parse(JSON.stringify(t.filter0))),e.cnvTested.content.push(JSON.parse(JSON.stringify(t.filter0)))),"CGC"==t.geneFilter&&(e.genesTable_filters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),e.cnvLossFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),e.cnvGainFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"})),e}}},3202:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>o});var r=n(4065);function s({genomes:t}){return(e,n)=>{try{e.query;const s=t[e.query.genome];if(!s)throw"invalid genome name";const o=(0,r.S)(s,e.query);n.send(o)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}}const o={endpoint:"genelookup",methods:{get:{init:s,request:{typeId:"GeneLookupRequest"},response:{typeId:"GeneLookupResponse"},examples:[{request:{body:{input:"kr",genome:"hg38-test"}},response:{header:{status:200},body:{hits:["KRAS"]}}}]},post:{alternativeFor:"get",init:s}}}},1746:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>s});var r=n(2062);const s={endpoint:"healthcheck",methods:{get:{init:({genomes:t})=>async(e,n)=>{try{const e=await(0,r.W)(t);n.send(e)}catch(t){n.send({status:"error",error:t.message||t})}},request:{typeId:null},response:{typeId:"HealthCheckResponse"}}}}},3932:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>c});var r=n(3345),s=n(2081),o=n(4521),i=n.n(o),a=n(334),l=n.n(a);const c={endpoint:"hicdata",methods:{get:{init:u,request:{typeId:"HicdataRequest"},response:{typeId:"HicdataResponse"}},post:{alternativeFor:"get",init:u}}};function u(){return async(t,e)=>{try{const n=await function(t){return new Promise(((e,n)=>{const[o,a,c]=(0,r.ZX)({query:t});o&&n({error:"illegal file name"});const u=["log(oe)"==t.matrixType?"oe":t.matrixType?t.matrixType:"observed",t.nmeth||"NONE",a,t.pos1,t.pos2,t.isfrag?"FRAG":"BP",t.resolution],f=(0,s.spawn)(l().hicstraw,u),d=i().createInterface({input:f.stdout}),h=[],p=[];let m=0,g=0;d.on("line",(e=>{const n=e.split("\t");if(3!=n.length)return void m++;const r=Number.parseInt(n[0]),s=Number.parseInt(n[1]),o="log(oe)"==t.matrixType?Math.log(Number.parseFloat(n[2])):Number.parseFloat(n[2]);Number.isNaN(r)||Number.isNaN(s)||Number.isNaN(o)?g++:null!=t.mincutoff&&o<=t.mincutoff||h.push([r,s,o])})),f.stderr.on("data",(t=>p.push(t))),f.on("close",(()=>{const t=p.join("");t&&n({error:t}),m&&n({error:m+" lines have other than 3 fields"}),g&&n({error:g+" lines have non-numerical values in any of the 3 fields"}),e({items:h})}))}))}(t.query);e.send(n)}catch(t){e.send({error:t?.message||t}),t instanceof Error&&t.stack&&console.log(t)}}}},6310:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>u});var r=n(3345),s=n(7147),o=n.n(s),i=n(6464),a=n.n(i),l=n(6452),c=n.n(l);const u={endpoint:"hicstat",methods:{get:{init:f,request:{typeId:"HicstatRequest"},response:{typeId:"HicstatResponse"},examples:[{request:{body:{genome:"hg19",file:"proteinpaint_demo/hg19/hic/hic_demo.hic",embedder:"localhost"}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:f}}};function f(){return async(t,e)=>{try{const[n,s,i]=(0,r.ZX)(t);if(n)throw"illegal file name";i||await(0,r.Ic)(s);const l=await async function(t,e){const n={},r=e?await S(t,0,32e3):await N(t,0,32e3),s=new DataView(r);let i=0;if("HIC"!==A())throw Error("Unsupported hic file");const l=M();if(7!==l&&8!==l&&9!=l)throw Error("Unsupported hic version: "+l);n.version=l;const u=Number(T());let f=[];const d=1e5;if(8==l||7==l){let e=await k(t,u,d);const n=e.getInt32(0,!0);n>0&&(e=await k(t,u+n+4,d),f=await q(e,u+n+4))}const h=A();if(n["Genome ID"]=h,9==l){const e=Number(T()),n=Number(T());if(e>0&&n>0){const r=await k(t,e,n);f=await q(r,0)}}const p={},m=M();let g=0;for(;g!==m;)p[A()]=A(),g++;n.Chromosomes={},n.chrorder=[];const y=M();let b=0;for(;b!==y;){const t=A();n.chrorder.push(t),n.Chromosomes[t]=7==l||8==l?M():T(),b++}n["Base pair-delimited resolutions"]=[];const v=M();let w=0;for(;w!==v;){const t=M();n["Base pair-delimited resolutions"].push(t),w++}n["Fragment-delimited resolutions"]=[];const _=M();let x=0;for(;x!==_;){const t=M();n["Fragment-delimited resolutions"].push(t),x++}return BigInt.prototype.toJSON||Object.defineProperty(BigInt.prototype,"toJSON",{get(){return()=>String(this)}}),n.normalization=f,n;async function k(t,n,r){const s=e?await S(t,n,r):await N(t,n,r);return new DataView(s)}async function q(e,n){const r=Date.now();let s=[];const o=e.getInt32(0,!0);let i=4;for(let t=1;t<=o;t++){let t=await f("string");s.push(t),8==l||7==l?(t=await f("string"),c(4),c(8*await f("int32")),c(12*await f("int32"))):9==l&&(i+=4,t=await f("string"),i+=20)}s=[...new Set(s)];const a=Date.now()-r;return console.log(`Read normalization on ${t} on ${a/1e3} seconds`),s;async function c(t){i+t>d&&u(),i+=t}async function u(){e=await k(t,n+i,d),n+=i,i=0}async function f(t){let n;if("string"==t){let t,r="";for(;i<e.byteLength&&0!=(t=e.getUint8(i++));)i>d&&await u(),r+=String.fromCharCode(t);n=r}else{if("int32"!=t)throw"No value assigned [server/src/hicstat.ts getViewValue()]";if(i<0)return;i+4>e.byteLength&&await u(),n=e.getInt32(i,!0),i+=4}return n}}async function N(t,e,n){const r=a().promisify(o().open),s=a().promisify(o().read),i=Buffer.alloc(n),l=await r(t,"r"),c=await s(l,i,0,n,e);o().close(l,(function(t){return t}));const u=c.buffer;return u.buffer.slice(u.byteOffset,u.byteOffset+u.byteLength)}async function S(t,e,n){try{const r=e+"-"+(e+n-1);return(await c()(t,{headers:{Range:"bytes="+r}}).buffer()).buffer}catch(t){throw console.log(t.response),"error reading file, check file details"}}function A(){let t,e="";for(;0!=(t=s.getUint8(i++));)e+=String.fromCharCode(t);return e}function 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async(e,n)=>{const o=e.query;try{const i=t[e.query.genome];if(!i)throw"invalid genome name";const l=i.datasets[e.query.dslabel];if(!l)throw"invalid dataset name";const c=l.cohort.termdb;if(!c)throw"invalid termdb object";await async function(t,e,n,o,i){if(!t.tid)throw".tid missing";const l="geneVariant"==t.type?{name:t.tid,type:"geneVariant",isleaf:!0}:n.q.termjsonByOneid(t.tid),c={filter:t.filter,terms:"geneVariant"==t.type?[{term:l,q:{isAtomic:!0}}]:[{id:t.tid,term:l,q:t.term1_q||a(l,t)}],currentGeneNames:t.currentGeneNames,rglst:t.rglst},u=await(0,s.Yu)(c,o,i);if(u.error)throw u.error;const f=[];if("geneVariant"==t.type){const e=u.samples,n=new Map;if(o.assayAvailability?.byDt)for(const[t,e]of Object.entries(o.assayAvailability.byDt))e.byOrigin&&n.set(parseInt(t),{byOrigin:{germline:{},somatic:{}}});const r=new Set;for(const[s,o]of Object.entries(e)){const e=o[t.tid].values;r.clear();for(const t of e){n.has(t.dt)||n.set(t.dt,{});const e=n.get(t.dt);e.byOrigin?(e.byOrigin[t.origin][t.class]||(e.byOrigin[t.origin][t.class]=1,r.add(`${t.dt} ${t.origin} ${t.class}`)),r.has(`${t.dt} ${t.origin} ${t.class}`)||(r.add(`${t.dt} ${t.origin} ${t.class}`),e.byOrigin[t.origin][t.class]+=1)):(e[t.class]||(r.add(`${t.dt} ${t.class}`),e[t.class]=1),r.has(`${t.dt} ${t.class}`)||(r.add(`${t.dt} ${t.class}`),e[t.class]+=1))}}for(const[t,e]of n)f.push({dt:t,classes:e})}else{const e=new Map;for(const n in u.samples){const r=u.samples[n][t.tid];r&&("key"in r&&e.set(r.key,1+(e.get(r.key)||0)))}for(const[n,r]of e)f.push({samplecount:r,key:n,label:u.refs?.byTermId?.[t.tid]?.events?.find((t=>t.event===n)).label||l?.values?.[n]?.label||n})}const d=(0,r.Tt)(l,u.refs?.byTermId?.[t.tid]?.bins||[],u.refs?.byTermId?.[t.tid]?.events,t.term1_q);d.length&&f.sort(((t,e)=>d.indexOf(t.label)-d.indexOf(e.label)));e.send({lst:f,orderedLabels:d})}(o,n,c,l,i)}catch(t){n.send({error:t?.message||t}),t instanceof Error&&t.stack&&console.log(t)}}}function a(t,e){if("categorical"==t.type)return{};if("survival"==t.type)return{};if("integer"==t.type||"float"==t.type)return t.bins.default;if("condition"==t.type)return{mode:e.mode,breaks:e.breaks,bar_by_grade:e.bar_by_grade,bar_by_children:e.bar_by_children,value_by_max_grade:e.value_by_max_grade,value_by_most_recent:e.value_by_most_recent,value_by_computable_grade:e.value_by_computable_grade};if("geneVariant"==t.type)return{};throw"unknown term type"}},4924:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>p,validate_query_geneExpression:()=>g});var r=n(1017),s=n.n(r),o=n(7147),i=n.n(o),a=n(9157),l=n(3345),c=n(334),u=n.n(c),f=n(1169),d=n(901),h=n(2273);const p={endpoint:"termdb/cluster",methods:{all:{init:function({genomes:t}){return async(e,n)=>{const r=e.query;let o;try{const e=t[r.genome];if(!e)throw"invalid genome name";const n=e.datasets[r.dslabel];if(!n)throw"invalid dataset name";if(n.__gdc&&!n.__gdc.doneCaching)throw"The server has not finished caching the case IDs: try again in ~2 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f=c.RowOrder.map((t=>r.row_names.indexOf(t.name))),d=c.ColOrder.map((t=>r.col_names.indexOf(t.name))),h=[];for(const t of f){const e=[];for(const n of d)e.push(r.matrix[t][n]);h.push(e)}return{row:{merge:c.RowMerge,height:c.RowHeight,order:c.RowOrder,inputOrder:r.row_names},col:{merge:c.ColumnMerge,height:c.ColumnHeight,order:c.ColOrder,inputOrder:r.col_names},matrix:h}}(n,t);u().debugmode&&console.log("clustering done:",Date.now()-c,"ms");return{clustering:f,byTermId:r,bySampleId:o}}(r,n)}catch(t){t.stack&&console.log(t.stack),o={status:t.status||400,error:t.message||t}}n.send(o)}},request:{typeId:"TermdbClusterRequest"},response:{typeId:"TermdbClusterResponse"}}}};function m(t){const e=t.reduce(((t,e)=>t+e),0)/t.length,n=Math.sqrt(t.reduce(((t,n)=>t+Math.pow(n-e,2)),0)/t.length);return 0==n?t:t.map((t=>(t-e)/n))}async function g(t,e){const n=t.queries.geneExpression;if(n)if("gdcapi"!=n.src){if("native"!=n.src)throw"unknown queries.geneExpression.src";await async function(t,e,n){t.file.startsWith(u().tpmasterdir)||(t.file=s().join(u().tpmasterdir,t.file));t.samples||(t.samples=[]);await l.LC(t.file),t.nochr=await l.Jy(t.file,null,n),t.samples=[];{const n=await l.ZD(t.file);if(!n[0])throw"header line missing from "+t.file;const r=n[0].split("\t");if("#chr\tstart\tstop\tgene"!=r.slice(0,4).join("\t"))throw"header line has wrong content for columns 1-4";for(let n=4;n<r.length;n++){const s=e.cohort.termdb.q.sampleName2id(r[n]);if(null==s)throw"queries.geneExpression: unknown sample from header: "+r[n];t.samples.push(s)}console.log(t.samples.length,"samples from geneExpression of",e.label)}t.get=async r=>{const s=await(0,d.T)(r,t.samples,e);if(0==s?.size)return{gene2sample2value:new Set,byTermId:{},bySampleId:{}};const o={},i=t.samples||[];if(s)for(const t of s)o[t]={label:e.cohort.termdb.q.id2sampleName(t)};else for(const t of i)o[t]={label:e.cohort.termdb.q.id2sampleName(t)};const a=new Map;for(const e of r.genes){if(!e.gene)continue;if(!e.chr){const t=n.genedb.getjsonbyname.all(e.gene);if(0==t.length)continue;const r=JSON.parse(t.find((t=>t.isdefault)).genemodel||t[0].genemodel);e.start=r.start,e.stop=r.stop,e.chr=r.chr}const r={};await l.UE({args:[t.file,(t.nochr?e.chr?.replace("chr",""):e.chr)+":"+e.start+"-"+e.stop],callback:t=>{const n=t.split("\t");if(n[3].toLowerCase()==e.gene.toLowerCase())for(let t=4;t<n.length;t++){const e=i[t-4];if(s&&!s.has(e))continue;if(!n[t])continue;const o=Number(n[t]);if(Number.isNaN(o))throw"exp value not number";r[e]=o}}}),Object.keys(r).length&&a.set(e.gene,r)}return{gene2sample2value:a,byTermId:{},bySampleId:o}}}(n,t,e)}else(0,f.eG)(t,e)}},2262:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>o});var r=n(8907),s=n(8615);const o={endpoint:"termdb/descrstats",methods:{all:{init:function({genomes:t}){return async(e,n)=>{const o=e.query;try{const i=t[e.query.genome];if(!i)throw"invalid genome name";const a=i.datasets[e.query.dslabel];if(!a)throw"invalid 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o={ds:s,term_id:t.tid,filter:t.filter},i=await r.tt(o);e.send({lst:i})}(s,n,a,i)}catch(t){n.send({error:t?.message||t}),t instanceof Error&&t.stack&&console.log(t)}}}},2630:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>o});var r=n(8907),s=n(7027);const o={endpoint:"termdb/getpercentile",methods:{get:{init:i,request:{typeId:"getpercentileRequest"},response:{typeId:"getpercentileResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",getpercentile:[50],tid:"agedx",filter:{type:"tvslst",in:!0,join:"",lst:[{tag:"cohortFilter",type:"tvs",tvs:{term:{name:"Cohort",type:"categorical",values:{ABC:{label:"ABC"},XYZ:{label:"XYZ"}},id:"subcohort",isleaf:!1,groupsetting:{disabled:!0}},values:[{key:"ABC",label:"ABC"}]}}]}}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:i}}};function i({genomes:t}){return async(e,n)=>{const o=e.query;try{const i=t[e.query.genome];if(!i)throw"invalid genome name";const a=i.datasets[e.query.dslabel];if(!a)throw"invalid dataset name";await async function(t,e,n){const o=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!o)throw"invalid termid";if("float"!=o.type&&"integer"!=o.type)throw"not numerical term";const i=t.getpercentile,a=[],l=[],c=await r.J4({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null});for(const{value:t}of c)o.values&&o.values[t]&&o.values[t].uncomputable||o.skip0forPercentile&&0==t||l.push(Number(t));for(const t of i){const e=(0,s.Z)(l,t);a.push(e)}e.send({values:a})}(o,n,a)}catch(t){n.send({error:t?.message||t}),t instanceof Error&&t.stack&&console.log(t)}}}},7095:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>s});var r=n(2826);const s={endpoint:"termdb/rootterm",methods:{get:{init:o,request:{typeId:"getroottermRequest"},response:{typeId:"getroottermResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",default_rootterm:1,cohortValues:"ABC"}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:o}}};function o({genomes:t}){return async(e,n)=>{const s=e.query;s.cohortValues&&s.cohortValues,s.treeFilter&&s.treeFilter;try{const o=t[e.query.genome];if(!o)throw"invalid genome name";const[i,a]=(0,r.pq)(o,s);if(!i)throw"invalid dataset name";if(!a)throw"invalid termdb object";await async function(t,e,n){const r=t.cohortValues?t.cohortValues:"",s=t.treeFilter?t.treeFilter:"";e.send({lst:await n.q.getRootTerms(r,s)})}(s,n,a)}catch(t){n.send({error:t?.message||t}),t instanceof Error&&t.stack&&console.log(t)}}}},3967:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>s});var r=n(2826);const s={endpoint:"termdb/termchildren",methods:{get:{init:o,request:{typeId:"gettermchildrenRequest"},response:{typeId:"gettermchildrenResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",get_children:1,cohortValues:"ABC",tid:"GO:0000001"}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:o}}};function o({genomes:t}){return async(e,n)=>{const s=e.query;try{const o=t[e.query.genome];if(!o)throw"invalid genome name";const[i,a]=await(0,r.pq)(o,s);if(!i)throw"invalid dataset name";if(!a)throw"invalid termdb object";await async function(t,e,n){if(!t.tid)throw"no parent term id";const s=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"",i=await n.q.getTermChildren(t.tid,s,o);e.send({lst:i.map(r.iK)})}(s,n,a)}catch(t){n.send({error:t?.message||t}),t instanceof Error&&t.stack&&console.log(t)}}}},3677:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>f,validate_query_singleSampleMutation:()=>d});var r=n(7147),s=n.n(r),o=n(1017),i=n.n(o),a=n(3345),l=n(334),c=n.n(l),u=n(1169);const f={endpoint:"termdb/singleSampleMutation",methods:{get:{init:function({genomes:t}){return async(e,n)=>{const r=e.query;let s;try{const e=t[r.genome];if(!e)throw"invalid genome name";const n=e.datasets[r.dslabel];if(!n)throw"invalid dataset name";if(!n.queries?.singleSampleMutation)throw"not supported on this dataset";s=await n.queries.singleSampleMutation.get(r)}catch(t){t.stack&&console.log(t.stack),s={status:t.status||400,error:t.message||t}}n.send(s)}},request:{typeId:"TermdbSingleSampleMutationRequest"},response:{typeId:"TermdbSingleSampleMutationResponse"}}}};async function d(t,e){const n=t.queries.singleSampleMutation;if(n)if("gdcapi"==n.src)(0,u.sV)(t,e);else{if("native"!=n.src)throw"unknown singleSampleMutation.src";n.get=async e=>{let r=e.sample;if(t.cohort?.termdb?.q?.sampleName2id&&(r=t.cohort.termdb.q.sampleName2id(e.sample),null==r))return[];const o=i().join(c().tpmasterdir,n.folder,r.toString());try{await s().promises.stat(o)}catch(t){if("EACCES"==t.code)throw"cannot read file, permission denied";if("ENOENT"==t.code)throw"no data for this sample";throw"failed to load data"}const l=await(0,a.b5)(o);return{mlst:JSON.parse(l)}}}}},5707:(t,e,n)=>{"use strict";n.r(e),n.d(e,{api:()=>r});const r={endpoint:"termdb/singlecellData",methods:{get:{init:s,request:{typeId:"TermdbSinglecellDataRequest"},response:{typeId:"TermdbSinglecellDataResponse"}},post:{alternativeFor:"get",init:s}}};function s({genomes:t}){return async(e,n)=>{const r=e.query;let s;try{const e=t[r.genome];if(!e)throw"invalid genome name";const n=e.datasets[r.dslabel];if(!n)throw"invalid dataset name";if(!n.queries?.singleCell)throw"no singlecell data on this dataset";s=await n.queries.singleCell.data.get(r)}catch(t){t.stack&&console.log(t),s={status:t.status||400,error:t.message||t}}n.send(s)}}},7934:(t,e,n)=>{"use 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"+t.sampletype):t.patient&&(t.sample=t.patient+" "+t.sampletype)}else t.patient?t.sample?t.sampletype=t.sample:t.sample=t.sampletype=t.patient:t.sample&&(t.sampletype=t.sample);if(t.origin){switch(t.origin.toLowerCase()){case"r":case"relapse":i=r.moriginrelapse,t.isrim2=!0;break;case"g":case"germline":i=r.morigingermline,t.isrim1=!0;break;case"gp":case"germline pathogenic":i=r.morigingermlinepathogenic,t.isrim1=!0;break;case"gnp":case"germline nonpathogenic":case"germline non-pathogenic":i=r.morigingermlinenonpathogenic,t.isrim1=!0;break;case"s":case"somatic":case"diagnosis":i=r.moriginsomatic}}if(t.origin=i,!t.sample&&!t.patient)return;const a="no patient/individual name";if(t.patient?(e.patient2st[t.patient]||(e.patient2st[t.patient]={}),e.patient2st[t.patient][t.sampletype]=t.sample):(e.patient2st[a]||(e.patient2st[a]={}),e.patient2st[a][t.sampletype]=t.sample),t.sample&&t.disease)if(t.sample in e.sample2disease){if(t.disease!=e.sample2disease[t.sample])return e.snv.badlines.push([n,'conflict of disease types for sample "'+t.sample+'": '+t.disease+", "+e.sample2disease[t.sample],s]),!0}else e.sample2disease[t.sample]=t.disease;return!1}},5494:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>o,parseline:()=>i});var r=n(2273),s=n(8064);function o(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid file header for snv/indel";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let s=r("annovar_gene","annovar_sj_gene","gene","genename","gene_symbol","hugo_symbol");return-1==s?"gene missing from header":(n[s]="gene",s=r("annovar_aachange","amino_acid_change","annovar_sj_aachange","aachange","protein_change","variant"),-1==s?"amino_acid_change missing from header":(n[s]="mname",s=r("annovar_class","class","mclass","variant_class","variant_classification","annovar_sj_class"),-1==s?"variant_class missing from header":(n[s]="class",s=r("chromosome","chr"),-1==s?"chromosome missing from 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0),a.gene2||(a.isoform2=void 0),a.gene1){n.good++;const t={dt:o?s.dtsv:s.dtfusionrna,class:o?s.mclasssv:s.mclassfusionrna,isoform:a.isoform1,mname:a.gene2||a.chr2,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene1.toUpperCase():a.gene1;n.data[e]||(n.data[e]=[]),n.data[e].push(t)}if(a.gene2&&a.gene2!=a.gene1){n.good++;const t={dt:o?s.dtsv:s.dtfusionrna,class:o?s.mclasssv:s.mclassfusionrna,isoform:a.isoform2,mname:a.gene1||a.chr1,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene2.toUpperCase():a.gene2;n.data[e]||(n.data[e]=[]),n.data[e].push(t)}}}else c.push([t,"missing position2",i])}function a(t){const e={};for(const n in t){if("pairlst"==n)continue;const r=t[n];"object"!=typeof r&&(e[n]=r)}if(t.pairlst){e.pairlst=[];for(const n of t.pairlst){const t={};for(const e in n)"a"!=e&&"b"!=e&&"interstitial"!=e&&(t[e]=n[e]);if(n.a){t.a={};for(const e in n.a){const r=n.a[e];"object"!=typeof r&&(t.a[e]=r)}}if(n.b){t.b={};for(const e in n.b){const r=n.b[e];"object"!=typeof r&&(t.b[e]=r)}}if(n.interstitial){t.interstitial={};for(const e in n.interstitial){const 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e={dt:r.dtfusionrna,class:r.mclassfusionrna,isoform:t.a.isoform,mname:t.b.name};for(const t in l)"jsontext"!=t&&(e[t]=l[t]);e.pairlst=a(u);const s=t.a.name.toUpperCase();n.data[s]||(n.data[s]=[]),n.data[s].push(e)}if(t.b&&t.b.name&&t.b.isoform){n.good++;const e={dt:r.dtfusionrna,class:r.mclassfusionrna,isoform:t.b.isoform,mname:t.a.name};for(const t in l)"jsontext"!=t&&(e[t]=l[t]);e.pairlst=a(u);const s=t.b.name.toUpperCase();n.data[s]||(n.data[s]=[]),n.data[s].push(e)}}else{switch(u.dt=u.typecode,delete u.typecode,u.dt){case r.dtitd:u.class=r.mclassitd,u.mname="ITD";break;case r.dtnloss:u.class=r.mclassnloss,u.mname="N-loss";break;case r.dtcloss:u.class=r.mclasscloss,u.mname="C-loss";break;case r.dtdel:u.class=r.mclassdel,u.mname="Del";break;case r.dtsv:u.class=r.mclasssv,u.mname="SV";break;default:return void c.push([t,"unknown datatype",i])}if(!u.gene)return void c.push([t,"json.gene missing",i]);n.good++;for(const t in l)"jsontext"!=t&&(u[t]=l[t]);const 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j;case"frame_shift_del":case"frame_shift_ins":return"F";case"in_frame_del":return"D";case"in_frame_ins":return"I";case"translation_start_site":return C;case"3'utr":return M;case"5'utr":return T;case"blank":return"Blank";default:return null}}k[j]={label:"NONCODING",color:"black",dt:f,desc:"Noncoding mutation.",key:j};const O="Fuserna";k[O]={label:"Fusion transcript",color:"#545454",dt:d,desc:"Marks the break points leading to fusion transcripts.<br><span style=\"font-size:150%\">&#9680;</span> - 3' end of the break point is fused to the 5' end of another break point in a different gene.<br><span style=\"font-size:150%\">&#9681;</span> - 5' end of the break point is fused to the 3' end of another break point in a different gene.",key:O};const I="SV";k[I]={label:"Structural variation",color:"#858585",dt:m,desc:"Structural variation detected in genomic DNA.",key:I};const R="CNV_amp";k[R]={label:"Copy number gain",color:"#e9a3c9",dt:p,desc:"Copy number gain",key:R};const F="CNV_loss";k[F]={label:"Copy number loss",color:"#a1d76a",dt:p,desc:"Copy number loss",key:F};const P="CNV_loh";k[P]={label:"LOH",color:"#12EDFC",dt:p,desc:"Loss of heterozygosity",key:P};const D="snv";k[D]={label:"SNV",color:"#92a2d4",dt:f,desc:"Single nucleotide variation",key:D};const L="mnv";k[L]={label:"MNV",color:"#92a2d4",dt:f,desc:"Multiple nucleotide variation",key:L};const $="insertion";k[$]={label:"Sequence insertion",color:"#bd8e91",dt:f,desc:"Sequence insertion",key:$};const z="deletion";k[z]={label:"Sequence deletion",color:"#b5a174",dt:f,desc:"Sequence deletion",key:z};const Z={[f]:k.M.color};function U(t={}){if(t.mclass)for(const e in t.mclass){k[e]||(k[e]={});for(const n in t.mclass[e])k[e][n]=t.mclass[e][n]}}const B=function(t){const e=t.toLowerCase().split(",");let 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t>=1e9?(t/1e9).toFixed(1)+" Gb":t>=1e7?Math.ceil(t/1e6)+" Mb":t>=1e6?(t/1e6).toFixed(1)+" Mb":t>=1e4?Math.ceil(t/1e3)+" Kb":t>=1e3?(t/1e3).toFixed(1)+" Kb":t+(e?"bytes":" bp")}const it={A:"#ca0020",T:"#f4a582",C:"#92c5de",G:"#0571b0"};function at(t){switch(t){case"A":return"T";case"T":return"A";case"C":return"G";case"G":return"C";case"a":return"t";case"t":return"a";case"c":return"g";case"g":return"c";default:return t}}function lt(t){const e=[];for(let n=t.length-1;n>=0;n--)e.push(at(t[n]));return e.join("")}function ct(t,e){const n={chr:t.chr,start:t.start,stop:t.stop,strand:t.strand,coding:[]};if(e.isskipexon||e.isaltexon)for(let r=0;r<t.exon.length;r++){const s=Math.max(t.codingstart,t.exon[r][0]),o=Math.min(t.codingstop,t.exon[r][1]);s>o||-1==e.skippedexon.indexOf(r)&&n.coding.push([s,o])}else if(e.a5ss||e.a3ss){const 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r=a.boxes.reduce(((t,e)=>t.start+t.len>e.start+e.len?t:e));if(r.start+r.len==o.boxes[0].start){t.strokeStyle=se,t.setLineDash([]),t.beginPath();const r=Math.floor(o.x1)+.5;t.moveTo(r,e.y),t.lineTo(r,e.y+n.stackheight),t.stroke()}}}else if(n.overlapRP_multirows){if(Xe(t,o,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=se,t.setLineDash([]),t.beginPath(),l.x<=a.x2&&o.x1<=i.width&&(t.moveTo(Math.max(o.x1,i.x),r),t.lineTo(Math.min(a.x2,l.width),r)),t.stroke()}}else Xe(t,o,e.y,n,r)}null!=e.__tempscore&&s().features.indel_read_alignment_scores&&(t.fillStyle="blue",t.font=n.stackheight+"pt Arial",t.fillText(e.__tempscore,r.regions[0].width-100,e.y+n.stackheight/2))}function Xe(t,e,n,r,s){const o=r.regions[e.ridx];o.width=r.widths[e.ridx];for(const s of e.boxes){const i=o.x+o.scale(s.start);if("P"!=s.opr&&"I"!=s.opr)if("H"!=s.opr)if("D"!=s.opr&&"N"!=s.opr)if("*"!=s.opr){if("X"!=s.opr&&"S"!=s.opr){if("M"!=s.opr&&"="!=s.opr)throw"unknown opr at 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o=Math.ceil(e.x2+xe);o<=r.width+n.stackheight/2&&(t.fillStyle="white",t.beginPath(),t.moveTo(o-n.stackheight/2,s),t.lineTo(o,s),t.lineTo(o,s+n.stackheight/2),t.lineTo(o-n.stackheight/2,s),t.closePath(),t.fill(),t.beginPath(),t.moveTo(o-n.stackheight/2,s+n.stackheight),t.lineTo(o,s+n.stackheight),t.lineTo(o,s+n.stackheight/2),t.lineTo(o-n.stackheight/2,s+n.stackheight),t.closePath(),t.fill())}else{const o=e.x1;o>=r.x&&(t.fillStyle="white",t.beginPath(),t.moveTo(o+n.stackheight/2,s),t.lineTo(o,s),t.lineTo(o,s+n.stackheight/2),t.lineTo(o+n.stackheight/2,s),t.closePath(),t.fill(),t.beginPath(),t.moveTo(o+n.stackheight/2,s+n.stackheight),t.lineTo(o,s+n.stackheight),t.lineTo(o,s+n.stackheight/2),t.lineTo(o+n.stackheight/2,s+n.stackheight),t.closePath(),t.fill())}}(t,e,r,o,n),e.rnext&&(o.to_qual||e.x2-e.x1>=20&&r.stackheight>=7&&(t.font=Math.min(te,Math.max(ee,r.stackheight-4))+"pt Arial",t.fillStyle="white",t.fillText((s.nochr?"chr":"")+e.rnext,(e.x1+e.x2)/2,n+r.stackheight/2,e.x2-e.x1)))}function Qe(t,e,n,r){for(const[t,n]of e.regions.entries()){if(!n.to_printnt)continue;const e=new Set;for(const s of r)for(const r of s.segments){if(r.ridx!=t)continue;const s=r.boxes.filter((t=>"I"==t.opr));if(s.length)for(const t of s)e.add(n.x+n.scale(t.start))}}for(const n of r)for(const r of n.segments){const s=e.regions[r.ridx],o=r.boxes.filter((t=>"I"==t.opr));if(o.length){t.font=Math.max(te,e.stackheight-2)+"pt Arial";for(const i of o){const o=s.x+s.scale(i.start);let a;i.qual?t.fillStyle=Qt(i.qual.reduce(((t,e)=>t+e),0)/i.qual.length/_e):t.fillStyle=Kt,a=""==i.s?i.len:1==i.s.length?i.s:i.s.length,t.fillText(a,o,n.y+e.stackheight*(r.on2ndrow||0)+e.stackheight/2)}}}}async function tn(t,e,n){const r=We(t.qual),s=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)for(let n=0;n<e.len;n++){t.seq[e.cidx+n];s.push('<td style="background:'+Ft(r[e.cidx+n]/_e)+'">'+t.seq[e.cidx+n]+"</td>")}const o=[];o.push('<li><span style="background:'+Ht+';color:white">This segment in template is unmapped</span></li>'),1&t.flag&&o.push("<li>Template has multiple segments</li>"),2&t.flag&&o.push("<li>Each segment properly aligned</li>"),16&t.flag&&o.push("<li>Reverse complemented</li>"),32&t.flag&&o.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&o.push("<li>This is the first segment in the template</li>"),128&t.flag&&o.push("<li>This is the last segment in the template</li>"),256&t.flag&&o.push("<li>Secondary alignment</li>"),512&t.flag&&o.push("<li>Not passing filters</li>"),1024&t.flag&&o.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&o.push("<li>Supplementary alignment</li>");let i={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center">\n\t\t\t  <tr style="color:white">${s.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE</span>: ${Math.abs(t.seq.length)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t  </div>\n\t\t  <ul style='padding-left:15px'>${o.join("")}</ul>`};return t.discord_unmapped2&&(i.unmapped_mate=!0),i}async function en(t,e,n){const r=t.boxes[0].start,s=t.boxes[t.boxes.length-1],o=s.start+s.len,i=await Je(e,n.chr+":"+(r+1)+"-"+o),a=We(t.qual);let l,c;if("*"==t.seq)l=["<td>Nucleotide sequence not available for this read</td>"],c=["<td></td>"];else{l=["<td>Reference</td>"],c=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)if("H"!=e.opr)if("I"!=e.opr)if("D"!=e.opr&&"N"!=e.opr)if("S"!=e.opr)if("M"!=e.opr&&"="!=e.opr&&"X"!=e.opr&&"*"!=e.opr);else for(let n=0;n<e.len;n++){const s=i[e.start-r+n],o=t.seq[e.cidx+n];l.push("<td>"+s+"</td>"),"*"==t.qual?c.push('<td style="color:black;background:'+(s.toUpperCase()==o.toUpperCase()?Ft:Ut)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+(s.toUpperCase()==o.toUpperCase()?Ft:Ut)(a[e.cidx+n]/_e)+'">'+t.seq[e.cidx+n]+"</td>")}else for(let n=0;n<e.len;n++)l.push("<td>"+i[e.start-r+n]+"</td>"),"*"==t.qual?c.push('<td style="background:'+Jt(1)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+Jt(a[e.cidx+n]/_e)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=Ce)l.push('<td style="font-size:.8em;opacity:.5;white-space:nowrap">'+e.len+" bp</td>"),c.push('<td style="color:black;white-space:nowrap">-----------</td>');else for(let t=0;t<e.len;t++)l.push("<td>"+i[e.start-r+t]+"</td>"),c.push('<td style="color:black">-</td>');else for(let n=e.cidx;n<e.cidx+e.len;n++)l.push("<td>-</td>"),"*"==t.qual?c.push('<td style="color:'+Kt+';background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:'+Kt+";background:"+Ft(a[n]/_e)+'">'+t.seq[n]+"</td>")}let u=0,f=0,d=[],h=[],p=0;for(const e of t.boxes)u=f,f+=e.len,"S"==e.opr&&(p=1,d.push(u),h.push(f));const m=[];t.rnext&&m.push('<li>Next segment on <span style="background:'+Pt+'">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:'+Lt+';color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:'+Vt+';color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:'+Lt+';color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:'+Vt+';color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:'+Ht+';color:white">Other segment in template is unmapped</span></li>'),1&t.flag&&m.push("<li>Template has multiple segments</li>"),2&t.flag&&m.push("<li>Each segment properly aligned</li>"),16&t.flag&&m.push("<li>Reverse complemented</li>"),32&t.flag&&m.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&m.push("<li>This is the first segment in the template</li>"),128&t.flag&&m.push("<li>This is the last segment in the template</li>"),256&t.flag&&m.push("<li>Secondary alignment</li>"),512&t.flag&&m.push("<li>Not passing filters</li>"),1024&t.flag&&m.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&m.push("<li>Supplementary alignment</li>");let g={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center;font-family:courier">\n\t\t\t  <tr style="opacity:.6">${l.join("")}</tr>\n\t\t\t  <tr style="color:white">${c.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">CHR</span>: ${n.chr.replace("chr","")},\n\t\t\t<span style="opacity:.5;font-size:.7em">START</span>: ${t.segstart_original+1},\n\t\t\t<span style="opacity:.5;font-size:.7em">STOP</span>: ${o},\n\t\t\t<span style="opacity:.5;font-size:.7em">READ LENGTH</span>: ${t.seq.length} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE LENGTH</span>: ${Math.abs(t.tlen)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t  </div>\n\t\t  <ul style='padding-left:15px'>${m.join("")}</ul>`,start_readpos:r+1,boxes:t.boxes,readpanel_DN_maxlength:Ce};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function nn(t){const e=yt().createHmac("md5",je),n=[t.get("X-Auth-Token")||t.cookies.sessionid,t.query.gdcFileUUID,t.query.gdcFilePosition];return e.update(n.join("")).digest("hex")+".bam"}async function rn(t){if(!t.query.gdcFileUUID||!t.query.gdcFilePosition||!t.query.file)throw"cannot download GDC BAM slice: request is unauthorized";const e=t.query.regions;if(!Array.isArray(e)||0==e.length)throw"req.query.regions[] not non-empty array";const n=[];for(const r of e){const e=await hn(r.chr,r.start,r.stop,t.query.gdcFileUUID,nn(t),t);n.push({filesize:e})}return n}const sn=s().features?.bamCache||{},on=sn.maxAge||72e5,an=sn.maxSize||5e9,ln=sn.checkWait||6e4;let cn,un=0;function fn(t=0){const e=Date.now()+t;if(cn){if(un&&un<=e+5)return;clearTimeout(cn),cn=void 0}un=e,console.log(`will trigger mayDeleteCacheFiles() in ${t} ms`),cn=setTimeout(dn,t)}async function dn(){console.log("checking for cached bam files to delete ...");try{const t=Date.now()-on,e=await m().promises.readdir(s().cachedir_bam),n=[];let r=0,o=0,i=0,a=0;for(const l of e){if(!l.endsWith(".bam")&&!l.endsWith(".bai"))continue;i++;const e=y().join(s().cachedir_bam,l),c=await m().promises.stat(e);if(!c.isFile())continue;const u=c.mtimeMs;u<t?(await m().promises.unlink(e),a++,o+=c.size):(n.push({path:e,time:u,size:c.size}),r+=c.size)}if(n.sort(((t,e)=>e.time-t.time)),r>=an){const t=Date.now()-ln;for(const e of n){if(e.time>t)break;if(await m().promises.unlink(e.path),e.deleted=!0,a++,o+=e.size,r-=e.size,r<an)break}}console.log(`deleted ${a} of ${i} cached bam files (${o} bytes deleted, ${r} remaining)`),cn=void 0,un=0;const l=r&&n.find((t=>!t.deleted));if(l){fn(ln+Math.round(r>=an?0:Math.max(0,l.time+on-Date.now())))}}catch(t){console.error("Error in mayDeleteCacheFiles(): "+t)}}async function hn(t,e,n,r,o,i){fn(ln);const{host:a,headers:l}=Oe(i.query.__genomes).getHostHeaders(i.query);l.compression=!1;const c=y().join(s().cachedir_bam,o),u=a.rest+"/slicing/view/"+r+"?region="+t+":"+e+"-"+n;try{const t=Math.round(Date.now()/1e3);if(await F.yE(c)){if(await Ot(v().stream(u,{method:"GET",headers:l}),m().createWriteStream(c)),await F.yE(c))throw"BAM file slice is 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Fn=n(9064),Pn=n(1575);const Dn="ssm_occurrence_centrics";async function Ln(t){const e=new Map,{host:n,headers:r}=t.getHostHeaders(),o=y().join(n.rest,"ssm_occurrences/_mapping");let i;try{const{body:t}=await(0,F.fk)(o,{headers:r});i=t}catch(t){throw console.log(t),"failed to get GDC API _mapping: "+(t.message||t)}if(!i._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(i.fields))throw".fields not array";if(!Array.isArray(i.nested))throw".nested not array";const a=new Set(i.nested);let l=0,c=0,u=0,f=0,d=0,h=0;for(const t of i.fields){if(Bn(t)){l++;continue}const n=t.split(".");for(let t=1;t<n.length;t++){const r=n.slice(0,t).join("."),s=r+"."+n[t],o=n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),l={id:s.toLowerCase(),name:o,included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){l.isleaf=!0;const t=i._mapping[Dn+"."+s];t&&("keyword"==t.type?(l.type="categorical",u++):"long"==t.type?(l.type="integer",f++):"double"==t.type?(l.type="float",d++):console.log("GDC !!! 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Unknown variable type: "+t.type)),l.type||c++,$n(l)}if(1==t);else if(l.parent_id=r,l.type){l.included_types_set.add(l.type);let t=e.get(r);for(;t&&(t.included_types_set.add(l.type),t.child_types_set.add(l.type),t.parent_id);)t=e.get(t.parent_id)}a.has(s)&&(l.isObjectList=!0),e.set(s,l)}}try{await async function(t,e){const n=[],r=new Map;for(const e of t.values()){if("integer"!=e.type&&"float"!=e.type)continue;if(Zn[e.id]){e.bins=Zn[e.id];continue}const t=e.id.replace("case.","").replace(/\./g,"__");r.set(t,e.id),n.push(t+" {\n\t\t   stats {\n\t\t\t\tMin : min\n\t\t\t\tMax: max\n\t\t\t\tMean: avg\n\t\t\t\tSD: std_deviation\n\t\t\t\tcount\n\t\t\t}\n\t\t\trange(ranges: $filters2) {\n\t\t\t  buckets {\n\t\t\t\tdoc_count\n\t\t\t\tkey\n\t\t\t  }\n\t\t\t}\n\t\t}")}if(0==n.length)throw"GDC: no numeric terms, should not happen";const s=`\n\t  query ContinuousAggregationQuery($caseFilters: FiltersArgument, $filters: FiltersArgument, $filters2: FiltersArgument) {\n\t  viewer {\n\t\texplore 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o=(s.Max-s.Min)/5,l="integer"==r.type?Math.ceil(o):o;r.bins={default:{mode:"discrete",type:"regular-bin",bin_size:l,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:s.Min+l}}},i++}console.log(`GDC default binning: ${i} assigned, ${a} unassigned`)}(e,t)}catch(t){throw console.log(t),"assignDefaultBins() failed: "+(t.message||t)}for(const t of e.values())t.type||h++,t.included_types=[...t.included_types_set],t.child_types=[...t.child_types_set],delete t.included_types_set,delete t.child_types_set;console.log("GDC dictionary:",e.size,"total variables,",l,"lines skipped,",c,"lines with unknown term type,","categorical="+u,"integer="+f,"float="+d,"parent="+h),Object.freeze(e),function(t,e){const n=t.cohort.termdb.q={};async function r(e,n){if(0==e.length||!n)return;const r=await t.termdb.termid2totalsize2.get(e.map((t=>t.id)),JSON.parse(n));for(const t of e)if(t){const e=r.get(t.id);"categorical"==t.type&&e?e.length?t.samplecount=e.map((t=>t[1])).reduce(((t,e)=>t+e)):(t.disabled=!0,t.samplecount=0):"integer"!=t.type&&"float"!=t.type||(t.samplecount=e.total,0==e.total&&(t.disabled=!0))}}n.getRootTerms=async(t,n=null)=>{const s=[];for(const t of e.values())null==t.parent_id&&s.push(JSON.parse(JSON.stringify(t)));return await r(s,n),s},n.getTermChildren=async(t,n=null,s=null)=>{const o=[];for(const n of e.values())n.parent_id==t&&o.push(JSON.parse(JSON.stringify(n)));return await r(o,s),o},n.findTermByName=async(t,n=null,s,o=null,i=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const a=[];for(const n of e.values())i&&!(0,Pn.CG)(n,i)||n.id.includes(t)&&a.push(JSON.parse(JSON.stringify(n)));return await r(a,o),a},n.getAncestorIDs=t=>{if(!e.has(t))return;const n=t.split("."),r=[];for(let t=1;t<n.length;t++)r.push(n.slice(0,t+1).join("."));return r},n.getAncestorNames=n.getAncestorIDs,n.termjsonByOneid=t=>{const n=e.get(t);return n?JSON.parse(JSON.stringify(n)):null},n.getSupportedChartTypes=()=>{const t={},n={};for(const r of e.values())r.type&&(r.cohort in t||(t[r.cohort]=["barchart","table","regression"],n[r.cohort]=0),"survival"!=r.type||t[r.cohort].includes("survival")||t[r.cohort].push("survival"),"condition"!=r.type||t[r.cohort].includes("cuminc")||t[r.cohort].push("cuminc"),"float"!=r.type&&"integer"!=r.type||(n[r.cohort]+=r.samplecount));for(const e in n)n[e]>0&&t[e].push("boxplot"),n[e]>1&&t[e].push("scatterplot");return t}}(t,e),t.cohort.termdb.termtypeByCohort=[],u&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),f&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),d&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),t.__gdc={aliquot2submitter:{cache:new Map,get:async e=>t.__gdc.aliquot2submitter.cache.has(e)?t.__gdc.aliquot2submitter.cache.get(e):e},map2caseid:{cache:new Map,get:e=>t.__gdc.map2caseid.cache.get(e)},caseid2submitter:new Map,caseIds:new Set,casesWithExpData:new Set,gdcOpenProjects:new Set,doneCaching:0};try{await async function(t){const e={filters:{op:"and",content:[{op:"=",content:{field:"access",value:"open"}},{op:"=",content:{field:"data_type",value:"Masked Somatic Mutation"}}]},facets:"cases.project.project_id",size:0},{host:n,headers:r}=t.getHostHeaders(),{body:s}=await(0,F.fk)(y().join(n.rest,"files"),{method:"POST",headers:r,body:e});if(!Array.isArray(s?.data?.aggregations?.["cases.project.project_id"]?.buckets))return void console.log("getting open project_id but return is not re.data.aggregations['cases.project.project_id'].buckets[]");for(const e of s.data.aggregations["cases.project.project_id"].buckets)e.key&&t.__gdc.gdcOpenProjects.add(e.key);console.log("GDC open-access projects:",t.__gdc.gdcOpenProjects.size)}(t)}catch(t){throw console.log(t),"getOpenProjects() failed: "+(t.message||t)}!async function(t){await async function(t){const{host:e,headers:n}=t.getHostHeaders();try{{const t=y().join(e.rest,"ssms"),n=await Gn(t);if(n)throw`${t} returns error code: ${n}`}{const t=y().join(e.rest,"ssm_occurrences"),n=await Gn(t);if(n)throw`${t} returns error code: ${n}`}{const t=y().join(e.rest,"cases"),n=await Gn(t);if(n)throw`${t} returns error code: ${n}`}{const t=y().join(e.rest,"files"),n=await Gn(t);if(n)throw`${t} returns error code: ${n}`}{const t=y().join(e.rest,"analysis/top_mutated_genes_by_project"),n=await Gn(t);if(n)throw`${t} returns error code: ${n}`}{const t=await async function(t,e){const n=new Date;try{const n="query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\tprimary_site {buckets { doc_count, key }}\n\t\t\t\t}\n\t\t\t}\n\t\t}}",r=await v().post(t,{headers:e,body:JSON.stringify({query:n,variables:{}})});if(r.statusCode>399)return r.statusCode}catch(e){if(console.log(e),e.code)return e.code;throw"see above error from graphql API "+t}console.log("GDC GraphQL API okay: "+t,new Date-n,"ms")}(e.graphql,JSON.parse(JSON.stringify(n)));if(t)throw`${e.graphql} returns error code: ${t}`}}catch(t){throw console.log(t),`\n##########################################\n#\n#   Some GDC API unavailable, see error above\n#   ${e.rest}\n#   ${e.graphql}\n#\n##########################################`}}(t);try{await async function(t){if("stopGdcCacheAliquot"in s().features){if(!Number.isInteger(s().features.stopGdcCacheAliquot))return void console.log("GDC: sample IDs are not cached!");console.log("GDC: running limited sample ID caching")}else console.log("GDC: caching complete sample ID mapping");const e=1e3,n=await Jn(t,1,0);if(!Number.isInteger(n))throw"totalCases not integer";const r=new Date;console.log("GDC: Start to cache sample IDs of",n,"cases...");for(let r=0;r<Math.ceil(n/e)&&(await Jn(t,e,1e3*r),!(Number.isInteger(s().features.stopGdcCacheAliquot)&&r>=s().features.stopGdcCacheAliquot));r++);await async function(t){const{host:e,headers:n}=t.getHostHeaders(),r=`${e.geneExp}/gene_expression/availability`;try{const e=[...t.__gdc.caseIds],{body:s}=await(0,F.fk)(r,{method:"post",headers:n,body:{case_ids:e,gene_ids:["ENSG00000141510"]}});if(!Array.isArray(s.cases?.details))throw"re.cases.details[] not array";for(const e of s.cases.details)e.has_gene_expression_values&&t.__gdc.casesWithExpData.add(e.case_id);delete t.__gdc.caseIds}catch(t){console.log("You don't have access to /gene_expression/availability/, you cannot run GDC hierCluster")}}(t),t.__gdc.doneCaching=!0,console.log("GDC: Done caching sample IDs. Time:",Math.ceil((new Date-r)/1e3),"s"),console.log("\t",t.__gdc.aliquot2submitter.cache.size,"aliquot IDs to sample submitter id,"),console.log("\t",t.__gdc.caseid2submitter.size,"case uuid to submitter id,"),console.log("\t",t.__gdc.map2caseid.cache.size,"different ids to case uuid,"),console.log("\t",t.__gdc.casesWithExpData.size,"cases with gene expression data.")}(t)}catch(t){throw t.stack&&console.log(t.stack),"cacheSampleIdMapping() failed: "+(t.message||t)}}(t)}function $n(t){"case.diagnoses.age_at_diagnosis"!=t.id||(t.valueConversion={scaleFactor:1/365,fromUnit:"day",toUnit:"year"})}const zn={default:{mode:"discrete",type:"regular-bin",bin_size:1,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:0},last_bin:{start:1,stopunbounded:!0}}},Zn={"case.diagnoses.age_at_diagnosis":{default:{type:"custom-bin",mode:"discrete",lst:[{startunbounded:!0,stop:10950,stopinclusive:!0,label:"<=30 years"},{start:10950,stop:21900,stopinclusive:!0,label:"30-60 years"},{start:21900,stopunbounded:!0,startinclusive:!1,label:">60years"}]}}};const Un=new Set(["case.consent_type","case.days_to_consent","case.days_to_index"]);function Bn(t){return!!(t.startsWith("ssm")||t.startsWith("case.observation")||t.startsWith("case.available_variation_data"))||(!(!t.endsWith("_id")||t.endsWith("project_id"))||(!!Un.has(t)||void 0))}async function Gn(t){try{const e=new Date,n=await v()(t);if(n.statusCode>399)return n.statusCode;console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){if(console.log("See error from",t),console.log(e),e.code)return e.code;throw"gdc api down: "+t}}async function Jn(t,e,n,r){const s=["fields=submitter_id,samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(r)s.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+r+'"]}}]}');else{if(!Number.isInteger(e)||!Number.isInteger(n))throw"size and from not 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Hn=n(4973),Wn=n(3625),Vn=n(478),Yn=n(8907),Kn=n(394);function Xn(t,e){if(e.updateAttr&&!t.label){for(const n of e.updateAttr){let e=t;for(const t of n)if(e)if("object"==typeof t)for(const n in t)e[n]=t[n];else e=e[t]}t.label&&delete e.updateAttr}}function Qn(t,e,n){if(!t.cohort?.db?.refresh)return;const r=t.cohort.db.refresh;delete t.cohort.db.refresh,e.get(`${n}/${r.route}`,(async(e,n)=>{n.send({label:t.label,files:[]})})),e.post(`${n}/${r.route}`,(async(e,n)=>{try{const r=t.cohort.db?.file?.startsWith(s().tpmasterdir)?t.cohort.db.file:y().join(s().tpmasterdir,t.cohort.db.file||""),o=e.body;if(!o.dbfile)throw"Updating input text files via the termdb-refresh page has been deprecated.Please use the buildTermdb.bundle.js. pipeline before triggering this route to replace the db file.";{const e=y().join(s().tpmasterdir,o.dbfile);if(!await m().stat(e))throw`dbfile not found: '${e}'`;const n=t.cohort.db.file_fullpath||r;if(e===n)throw"db file source and target are the same";console.log(`copying ${e} to ${n}`),await m().copyFile(e,n)}await fr(t),n.send({status:"ok"})}catch(t){console.log(t),n.send({error:t.error||t})}}))}var tr=n(2188),er=n(2974),nr=n(3795),rr=n(7934),sr=n(5057),or=n(3677),ir=n(4924),ar=n(901);const lr="Unannotated";async function cr(t,e,n,r=null,o=null){await fr(t),t.queries&&(await async function(t,e){const n=t.queries.snvindel;if(!n)return;if(n.url){if(!n.url.base)throw".snvindel.url.base missing";if(!n.url.key)throw".snvindel.url.key missing"}if(!n.byisoform&&!n.byrange)throw"byisoform and byrange are both missing on queries.snvindel";if(n.byrange)if(n.byrange.gdcapi)bn.xq(t);else if(n.byrange.bcffile)n.byrange.bcffile=n.byrange.bcffile.startsWith(s().tpmasterdir)?n.byrange.bcffile:y().join(s().tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await pr(t,e),n.byrange._tk?.samples.length||delete n.byrange._tk.samples,hr(t,n.byrange._tk.samples,"snvindel.byrange.bcffile");else{if(!n.byrange.chr2bcffile)throw"unknown query method for queries.snvindel.byrange";n.byrange._tk={chr2files:{}};for(const t in n.byrange.chr2bcffile)n.byrange._tk.chr2files[t]={file:y().join(s().tpmasterdir,n.byrange.chr2bcffile[t])};delete n.byrange.chr2bcffile,n.byrange.get=await pr(t,e),n.byrange._tk.samples.length||delete n.byrange._tk.samples,hr(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";bn.CN(t)}if(n.m2csq){if(!n.m2csq.by)throw".by missing from queries.snvindel.m2csq";if("ssm_id"!=n.m2csq.by)throw"unknown value of queries.snvindel.m2csq.by";if(!n.m2csq.gdcapi)throw"unknown query method for queries.snvindel.m2csq";bn.wm(t)}}(t,e),await async function(t,e){const n=t.queries.svfusion;if(!n)return;if(!n.byrange)throw"byrange missing from queries.svfusion";if(n.byrange){if(!n.byrange.file)throw"unknown query method for svfusion.byrange";n.byrange.file=n.byrange.file.startsWith(s().tpmasterdir)?n.byrange.file:y().join(s().tpmasterdir,n.byrange.file),n.byrange.get=await async function(t,e){const n=t.queries.svfusion.byrange;if(n.file)await F.LC(n.file);else{if(!n.url)throw"file and url both missing on svfusion.byrange{}";n.dir=await F.d1(n.url,n.indexURL)}n.nochr=await F.Jy(n.file||n.url,null,e);{const t=await F.ZD(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}return async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const r=mr(e),s=await(0,ar.T)(e,n.samples,t);if(0==s?.size)return[];const o=new Map;for(const t of e.rglst)await F.UE({args:[n.file||n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const i=n.split("\t"),a=Number(i[1]);let l,c,u,f,d;try{l=JSON.parse(i[3])}catch(t){return}if(l.dt!=P.dtfusionrna&&l.dt!=P.dtsv)return;if(l.class=l.dt==P.dtsv?P.mclasssv:P.mclassfusionrna,e.hiddenmclass&&e.hiddenmclass.has(l.class))return;if(l.sample&&s&&!s.has(l.sample))return;if(l.chrA)c=1,u=l.geneA||l.chrA,f=l.strandA,d=[{a:{chr:l.chrA,pos:l.posA,strand:l.strandA,name:l.geneA},b:{chr:t.chr,pos:a,strand:l.strandB,name:l.geneB}}];else if(l.chrB)c=0,u=l.geneB||l.chrB,f=l.strandB,d=[{a:{chr:t.chr,pos:a,strand:l.strandA,name:l.geneA},b:{chr:l.chrB,pos:l.posB,strand:l.strandB,name:l.geneB}}];else{if(!l.pairlst)throw"missing chrA and chrB";{d=l.pairlst;const t=l.pairlst.findIndex((t=>t.chr==chr&&t.pos==a));if(-1==t)throw"current point missing from pairlst";c=t}}const h=[l.dt,t.chr,a,f,c,encodeURIComponent(u)].join(Hn.dq);let p;if(l.sample&&(p={sample_id:l.sample},l.mattr)){if(r)for(const t in r){const e=t in l.mattr?l.mattr[t]:lr;if(r[t].has(e))return}e.addFormatValues&&(p.formatK2v=l.mattr)}o.has(h)||o.set(h,{ssm_id:h,dt:l.dt,class:l.class,chr:t.chr,pos:a,strand:f,pairlstIdx:c,mname:u,pairlst:d,samples:[]}),p&&o.get(h).samples.push(p)}});return[...o.values()]}}(t,e),hr(t,n.byrange.samples,"svfusion.byrange")}}(t,e),await async function(t,e){const n=t.queries.geneCnv;if(!n)return;if(!n.bygene)throw"geneCnv.bygene missing";n.bygene.gdcapi&&bn.IK(t)}(t),await async function(t,e){const n=t.queries.cnv;if(!n)return;if(!n.byrange)throw"queries.cnv.byrange{} missing";if("native"==n.byrange.src){if(!n.byrange.file)throw"cnv.byrange.file missing when src=native";return n.byrange.file=n.byrange.file.startsWith(s().tpmasterdir)?n.byrange.file:y().join(s().tpmasterdir,n.byrange.file),n.byrange.get=await async function(t,e){const n=t.queries.cnv.byrange;if(n.file)await F.LC(n.file);else{if(!n.url)throw"file and url 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i=n.split("\t"),a=Number(i[1]),l=Number(i[2]);if(e.cnvMaxLength&&l-a>=e.cnvMaxLength)return;let c;try{c=JSON.parse(i[3])}catch(t){return}if(c.dt==P.dtcnv){if(c.chr=t.chr,c.start=a,c.stop=l,Number.isFinite(c.value)){if(c.value>0&&e.cnvGainCutoff&&c.value<e.cnvGainCutoff)return;if(c.value<0&&e.cnvLossCutoff&&c.value>e.cnvLossCutoff)return;c.class=c.value>0?P.mclasscnvgain:P.mclasscnvloss}else if(c.class!=P.mclasscnvgain&&c.class!=P.mclasscnvloss)return;if(c.ssm_id=[t.chr,c.start,c.stop,c.class].join(Hn.dq),(!e.hiddenmclass||!e.hiddenmclass.has(c.class))&&(!c.sample||!s||s.has(c.sample))){if(c.sample){const t={sample_id:c.sample};if(c.mattr){if(r)for(const t in r){const e=t in c.mattr?c.mattr[t]:lr;if(r[t].has(e))return}e.addFormatValues&&(t.formatK2v=c.mattr)}delete c.sample,c.samples=[t]}o.push(c)}}}});return o}}(t,e),void hr(t,n.byrange.samples,"cnv.byrange")}throw"unknown cnv.byrange.src"}(t,e),await async function(t,e){const n=t.queries.ld;if(!n)return;if(!Array.isArray(n.tracks)||!n.tracks.length)throw"ld.tracks[] not nonempty array";for(const t of n.tracks){if(!t.name)throw"name missing from one of ld.tracks[]";if(!t.file)throw".file missing from one of ld.tracks[]";t.file0=t.file,t.file=y().join(s().tpmasterdir,t.file),await F.LC(t.file),t.nochr=await F.Jy(t.file,null,e)}if(!n.overlay)throw"ld.overlay{} missing";if(!n.overlay.color_0)throw"ld.overlay.color_0 missing";if(!n.overlay.color_1)throw"ld.overlay.color_1 missing"}(t,e),await(0,ir.validate_query_geneExpression)(t,e),await async function(t,e){const n=t.queries.rnaseqGeneCount;if(!n)return;if(!n.file)throw"unknown data type for rnaseqGeneCount";n.file=y().join(s().tpmasterdir,n.file);{const e=(await(r=n.file,new Promise(((t,e)=>{const n=[],s=[],o=(0,q.spawn)("head",["-1",r]);o.stdout.on("data",(t=>n.push(t.toString()))),o.stderr.on("data",(t=>s.push(t.toString()))),o.on("error",(t=>{s.length&&e(s.join(""))})),o.on("close",(r=>{0!=r&&e("head command exited with non-zero status and this error: "+s.join("")),t(n.join(""))}))})))).trim().split("\t").slice(4);n.allSampleSet=new Set(e);const s=[];for(const e of n.allSampleSet)t.cohort.termdb.q.sampleName2id(e)||s.push(e);console.log(n.allSampleSet.size,`rnaseqGeneCount samples from ${t.label}`)}var r;n.get=async function(e){if(2!=e.samplelst?.groups?.length)throw".samplelst.groups.length!=2";if(e.samplelst.groups[0].values?.length<1)throw"samplelst.groups[0].values.length<1";if(e.samplelst.groups[1].values?.length<1)throw"samplelst.groups[1].values.length<1";const r=[];let o=0;for(const s of e.samplelst.groups[0].values){if(!Number.isInteger(s.sampleId))continue;const e=t.cohort.termdb.q.id2sampleName(s.sampleId);e&&(n.allSampleSet.has(e)?r.push(e):o+=1)}const i=[];let a=0;for(const r of e.samplelst.groups[1].values){if(!Number.isInteger(r.sampleId))continue;const e=t.cohort.termdb.q.id2sampleName(r.sampleId);e&&(n.allSampleSet.has(e)?i.push(e):a+=1)}const l=r.length,c=i.length;if(l<1)throw"sample size of group1 < 1";if(c<1)throw"sample size of group2 < 1";const u={case:r.map((t=>t)).join(","),control:i.map((t=>t)).join(","),input_file:n.file,output_path:y().join(s().binpath,"utils")},f=8;let d;if(r.length<=f&&i.length<=f||"edgeR"==e.method){const t=new Date,n=(await async function(t,e){return new Promise(((n,r)=>{y().join(s().Rscript,t);const o=(0,q.spawn)(s().Rscript,[t]),i=[],a=[];try{at.Readable.from(e).pipe(o.stdin)}catch(e){o.kill();let n=e;a.length&&(n+=`killed edgeR('${t}'), stderr: ${a.join("").trim()}`),r(n)}o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>a.push(t))),o.on("error",(e=>{a.length&&console.log(`edgeR('${t}') ps.on('error') stderr:`,a),r(e)})),o.on("close",(e=>{0!==e?r(`spawned '${t}' exited with a non-zero status and this stderr:\n${a.join("")}`):n(i.toString())}))}))}(y().join(s().binpath,"utils","edge.R"),JSON.stringify(u)),new Date);console.log("Time taken to run edgeR:",n-t,"ms"),e.method="edgeR";const r=y().join(s().binpath,"utils","r_output.txt");d=JSON.parse(m().readFileSync(r,"utf8")),m().unlink(r,(()=>{}))}else if("wilcoxon"==e.method){const t=new Date,n=await(0,Q.run_rust)("DEanalysis",JSON.stringify(u)),r=new Date;for(const t of n.split("\n"))t.startsWith("adjusted_p_values:")&&(d=JSON.parse(t.replace("adjusted_p_values:","")));console.log("Time taken to run rust DE pipeline:",r-t,"ms"),e.method="wilcoxon"}else{const t=new Date,n=await(0,Q.run_rust)("DEanalysis",JSON.stringify(u)),r=new Date;for(const t of n.split("\n"))t.startsWith("adjusted_p_values:")&&(d=JSON.parse(t.replace("adjusted_p_values:","")));console.log("Time taken to run rust DE pipeline:",r-t,"ms"),e.method="wilcoxon"}return{data:d,sample_size1:l,sample_size2:c,method:e.method}}}(t),await(0,or.validate_query_singleSampleMutation)(t,e),await async function(t,e){const n=t.queries.singleSampleGenomeQuantification;if(!n)return;for(const r in n){if(!Number.isFinite(n[r].min))throw"min not a number";if(!Number.isFinite(n[r].max))throw"max not a number";if(n[r].min>=n[r].max)throw"min>=max";if(!n[r].folder)throw"unknown query method for singleSampleGenomeQuantification";n[r].get=async(o,i)=>{let a=o;if(t.cohort?.termdb?.q?.sampleName2id&&(a=t.cohort.termdb.q.sampleName2id(o),null==a))return[];const l=y().join(s().tpmasterdir,n[r].folder,a.toString());try{await m().promises.stat(l)}catch(t){if("EACCES"==t.code)throw"cannot read file, permission denied";if("ENOENT"==t.code)throw"no data for this sample";throw"failed to load data"}return await wr(l,e,n[r],i)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGbtk;if(!n)return;for(const e in n){if(!Number.isFinite(n[e].min))throw"min not a number";if(!Number.isFinite(n[e].max))throw"max not a number";if(n[e].min>=n[e].max)throw"min>=max";if(!n[e].folder)throw"unknown query method for singleSampleGbtk";n[e].get=async r=>{let o=r;if(t.cohort?.termdb?.q?.sampleName2id&&(o=t.cohort.termdb.q.sampleName2id(r),null==o))return{};const i=y().join(n[e].folder,o+".gz");try{return await m().promises.stat(y().join(s().tpmasterdir,i)),{path:i}}catch(t){return{}}}}}(t),await(0,rr.validate_query_singleCell)(t,e),await(0,sr.validate_query_TopVariablyExpressedGenes)(t,e),await(0,Hn.uK)(t),await function(t){if(!t.ssm2canonicalisoform)return;if(t.ssm2canonicalisoform.gdcapi)return void bn.vK(t.ssm2canonicalisoform,t.getHostHeaders);throw"ssm2canonicalisoform.gdcapi is false"}(t),await function(t,e){if(!e.genedb.hasTable_refseq2ensembl)return;t.refseq2ensembl_query=e.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?")}(t,e),await function(t,e){if(!t.queries.snvindel&&!t.queries.svfusion&&!t.queries.geneCnv)return;t.mayGetGeneVariantData=async(n,r)=>{if("object"!=typeof n.term)throw"tw.term{} is not object";if("geneVariant"!=n.term.type)throw"tw.term.type is not geneVariant";if("string"!=typeof n.term.name)throw"tw.term.name is not string";if(!n.term.name)throw"tw.term.name should be gene symbol but is empty string";const s=[];if("snp"==n.term.subtype){if(!t.queries.snvindel?.allowSNPs)throw"snvindel does not allow snp";const o=(await kr(t,n.term,e,r)).find((t=>n.term.alleles.includes(t.ref)&&n.term.alleles.includes(t.alt)));if(o){const t=[];for(const e of o.samples){if(!e.formatK2v?.GT)continue;const n=[];for(const t of e.formatK2v.GT.split("/"))0==t?n.push(o.ref):1==t?n.push(o.alt):console.log("unknown allele idx");n.join("/"),n.join("/");t.push({sample_id:e.sample_id,GT:n.join("/")})}const e={samples:t};s.push(e)}}else{if(t.queries.snvindel){const o=await kr(t,n.term,e,r);s.push(...o)}if(t.queries.svfusion){const o=await async function(t,e,n,r){const s={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,sessionid:r.sessionid};if(t.queries.svfusion.byrange)return await xr(e,n),s.rglst=[e],await t.queries.svfusion.byrange.get(s);throw"unknown queries.svfusion method"}(t,n.term,e,r);s.push(...o)}if(t.queries.cnv){const o=await async function(t,e,n,r){const s={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,cnvMaxLength:e?.q?.cnvMaxLength,cnvGainCutoff:e?.q?.cnvGainCutoff,cnvLossCutoff:e?.q?.cnvLossCutoff,sessionid:r.sessionid};if(t.queries.cnv.byrange)return await xr(e.term,n),s.rglst=[e.term],await t.queries.cnv.byrange.get(s);throw"unknown queries.cnv method"}(t,n,e,r);s.push(...o)}if(t.queries.geneCnv){const e=await async function(t,e,n,r){const s={filter0:r.filter0,sessionid:r.sessionid};if(t.queries.geneCnv.bygene)return e.name?(s.gene=e.name,await t.queries.geneCnv.bygene.get(s)):[];throw"unknown queries.geneCnv method"}(t,n.term,0,r);s.push(...e)}}const o=new Map;for(const t of s)if(Array.isArray(t.samples))for(const e of t.samples){o.has(e.sample_id)||o.set(e.sample_id,{sample:e.sample_id}),o.get(e.sample_id)[n.term.name]||(o.get(e.sample_id)[n.term.name]={key:n.term.name,label:n.term.name,values:[]});const r={gene:n.term.name,isoform:t.isoform,dt:t.dt,chr:n.term.chr,class:t.class,pos:t.pos||(t.start?t.start+"-"+t.stop:""),mname:t.mname};if("value"in t&&(r.value=t.value),e.formatK2v)for(const t in e.formatK2v)r[t]=e.formatK2v[t];t.dt==P.dtsnvindel?e.GT&&(r.value=e.GT,r.key=e.GT):t.dt!=P.dtfusionrna&&t.dt!=P.dtsv||(r.pairlst=t.pairlst),o.get(e.sample_id)[n.term.name].values.push(r)}return await async function(t,e,n,r){if(!e.assayAvailability?.byDt)return;const s=t.filter?new Set((await(0,Yn.cf)(t.filter,e)).map((t=>t.id))):null;for(const t in e.assayAvailability.byDt){const o=e.assayAvailability.byDt[t];if(o.byOrigin)for(const e in o.byOrigin){_r(t,o.byOrigin[e],n,r,e,s)}else _r(t,o,n,r,!1,s)}}(r,t,o,n.term.name),o}}(t,e)),await function(t){if(!t.assayAvailability)return;if(t.assayAvailability.byDt)for(const e in t.assayAvailability.byDt){const n=t.assayAvailability.byDt[e];if(n.byOrigin)for(const e in n.byOrigin){const r=n.byOrigin[e];if(!r.yes||!r.no||!r.term_id)throw"ds.assayAvailability.byDt.*.byOrigin properties require .term_id .yes{} .no{}";qr(t,r)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";qr(t,n)}}}(t),await function(t){if(!t.viewModes)return;if(!Array.isArray(t.viewModes))throw"ds.viewModes[] not array";for(const e of t.viewModes)if(e.byInfo){if(!t?.queries?.snvindel?.info)throw"view mode byInfo but queries.snvindel.info missing";const n=t.queries.snvindel.info[e.byInfo];if(!n)throw"unknown INFO field for viewmode byInfo";if("Float"!=n.Type&&"Integer"!=n.Type)throw"viewmode byInfo Type is not numeric";e.type="numeric",e.label=e.byInfo}else if(!e.byAttribute)throw"view mode not byInfo or byAttribute"}(t),t.cohort?.db?.refresh&&r&&await Qn(t,r,o)}function ur(t){const e={isMds3:!0,label:t.label};if(t.viewModes&&(e.skewerModes=t.viewModes),t.noGenomicMode4lollipopTk&&(e.noGenomicMode4lollipopTk=!0),function(t,e){if(!t.queries)return;const n={};t.queries.singleSampleMutation&&(n.singleSampleMutation={sample_id_key:t.queries.singleSampleMutation.sample_id_key,discoSkipChrM:t.queries.singleSampleMutation.discoSkipChrM});if(t.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const e in t.queries.singleSampleGenomeQuantification)n.singleSampleGenomeQuantification[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGenomeQuantification[e])),delete n.singleSampleGenomeQuantification[e].folder}if(t.queries.singleSampleGbtk){n.singleSampleGbtk={};for(const e in t.queries.singleSampleGbtk)n.singleSampleGbtk[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGbtk[e])),delete n.singleSampleGbtk[e].folder}const r=t.queries.snvindel;r&&(e.has_skewer=!0,n.snvindel={forTrack:r.forTrack,vcfid4skewerName:r.vcfid4skewerName,skewerRim:r.skewerRim,ssmUrl:r.ssmUrl},r.m2csq&&(n.snvindel.m2csq={by:r.m2csq.by}),r.info&&(e.bcf={info:r.info}),r.format&&(e.bcf||(e.bcf={}),e.bcf.format=r.format));if(t.queries.ld){n.ld=JSON.parse(JSON.stringify(t.queries.ld));for(const t of n.ld.tracks)delete t.file}e.queries=n}(t,e),t.cohort?.termdb&&(e.termdb={},t.cohort.termdb.allowCaseDetails&&(e.termdb.allowCaseDetails={sample_id_key:t.cohort.termdb.allowCaseDetails.sample_id_key})),t.variant2samples){const n=t.variant2samples;e.variant2samples={sunburst_twLst:n.sunburst_twLst,twLst:n.twLst,type_samples:n.type_samples,type_summary:n.type_summary,type_sunburst:n.type_sunburst,variantkey:n.variantkey}}return e}async function fr(t){if(t.cohort){if(!t.cohort.termdb)throw"ds.cohort is set but cohort.termdb{} missing";if(!t.cohort.db)throw"ds.cohort is set but cohort.db{} missing";if(!t.cohort.db.file&&!t.cohort.db.file_fullpath)throw"ds.cohort.db.file missing"}else{if(!t.termdb)return;t.cohort={},t.cohort.termdb=t.termdb,delete t.termdb}const e=t.cohort.termdb;if(e?.dictionary?.gdcapi)await Ln(t);else if(e?.dictionary?.dbFile)t.cohort.db={file:e.dictionary.dbFile},delete e.dictionary.dbFile,(0,Kn.JV)(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";(0,Kn.JV)(t)}if(e.termid2totalsize2&&(e.termid2totalsize2.gdcapi,e.termid2totalsize2.get=async(n,r={},s=null)=>e.termid2totalsize2.gdcapi?await bn.ws(n,r,s,t):await async function(t,e,n,r){const s=dr(e,r),o=new Map;for(const e of t)if(e.term&&"categorical"==e.term.type){const t={term1_id:e.id,term1_q:{type:"values"},filter:s},n=await(0,ot.e8)(t,r,r.cohort.termdb);if(!n?.data?.charts?.[0])continue;const i=[];for(const t of n.data.charts[0].serieses)i.push([t.seriesId,t.total]);o.set(e.id,i)}return n?[o,n]:o}(n,r,s,t)),function(t){const e=t.selectCohort;if(!e)return;if("object"!=typeof e)throw"selectCohort{} not object";if(!e.term)throw"term{} missing from termdb.selectCohort";if(!e.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof e.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=e.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';{const n=t.q.termjsonByOneid(e.term.id);if(!n)throw"termdb.selectCohort.term.id is invalid";if("categorical"!=n.type)throw"termdb.selectCohort.term type is not categorical"}if(!e.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(e.values))throw"termdb.selectCohort.values is not array";if(0==e.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const t of e.values){if(!t.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(t.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==t.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}(e),await async function(t){if(!t.restrictAncestries)return;if(!Array.isArray(t.restrictAncestries)||0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!e.tvs.term)throw"tvs.term{} missing from an ancestry";if(!e.tvs.term.id)throw"tvs.term.id missing from an ancestry";{const n=t.q.termjsonByOneid(e.tvs.term.id);if(!n)throw"tvs.term.id is invalid from an ancestry";if("categorical"!=n.type)throw"tvs.term.type is not categorical from an ancestry"}if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCcount<=1)throw"PCcount must be greater than 1";if(e.PCTermId){e.pcs=new Map;for(let n=1;n<=e.PCcount;n++){const r=e.PCTermId+n,s=t.q.termjsonByOneid(r);if(!s)throw"a PC term is not found in termdb";const o=t.q.getAllValues4term(r);if(!o||!o.size)throw"no sample PC values are retrieved by restrictAncestries term: "+r;e.pcs.set(s.name,o)}}else{if(!e.PCBySubcohort)throw"unknown PC source and configuration for restrictAncestries";for(const n in e.PCBySubcohort){let r=!0;for(const e of t.selectCohort.values)if(n==e.keys.sort().join(",")){r=!1;break}if(r)throw"unknown subcohort from PCBySubcohort";const s=e.PCBySubcohort[n];if(!s.termId)throw"termId missing from a subcohort of PCBySubcohort";s.pcs=new Map;for(let n=1;n<=e.PCcount;n++){const e=s.termId+n,r=t.q.termjsonByOneid(e);if(!r)throw"a PC term is not found in termdb";const o=t.q.getAllValues4term(e);if(!o||!o.size)throw"no sample PC values are retrieved by restrictAncestries.PCBySubcohort.<>.termId";s.pcs.set(r.name,o)}}}}}(e),await(0,tr.wz)(t),await(0,er.te)(t),"minTimeSinceDx"in e){if(!Number.isFinite(e.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(e.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in e){if(!Number.isFinite(e.ageEndOffset))throw"termdb.ageEndOffset not number";if(e.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(e.convertSampleId){if(!e.convertSampleId.gdcapi)throw"unknown implementation of tdb.convertSampleId";bn.Ak(e,t)}if(await async function(t){if(!t.cohort?.cumburden)return;t.cohort.cumburden.files;const e=t.cohort.cumburden.files;for(const t of["fit","surv","sample"]){const n=e[t];if(!n)throw`missing ds.cohort.burden.files.${t}`;const r=(0,q.spawnSync)(s().Rscript,["-e",`load('${s().tpmasterdir}/${n}')`],{encoding:"utf-8"});if(r?.status||r?.stderr)throw console.log(r),`error with ds.cohort.cumburden.files.${t}`}}(t),t.cohort?.db?.connection){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT * FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[sampleId]=t.sampleId2Name.get(+sampleId);return n}}if(t.cohort.mutationset){const{mayGetGeneVariantData:e,getTermTypes:r,mayGetMatchingGeneNames:s}=n(7833);t.mayGetGeneVariantData=e,t.getTermTypes=r,t.mayGetMatchingGeneNames=s}}function dr(t,e){const n=[];if(t.filterObj&&n.push(t.filterObj),t.tid2value&&n.push((0,ar.w)(t.tid2value,e)),0!=n.length)return 1==n.length?n[0]:(0,Vn.xH)(n)}function hr(t,e,n){if(!e)return;let r;if(t?.cohort?.termdb){for(const t of e){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer sample id from "+n;t.name=e}r=", all integer IDs"}console.log(e.length,"samples from "+n+" of "+t.label+r)}async function pr(t,e){const n=t.queries.snvindel.byrange;if(n._tk.file)await F._H(n._tk,e,!0);else if(n._tk.chr2files){let t;for(const r in n._tk.chr2files){if("chr17"!=r)continue;const s=n._tk.chr2files[r];try{await F._H(s,e,!0);const o=JSON.stringify(s.samples);if(t){if(o!=t)throw"Different samples found in bcf file of "+r}else t=o,n._tk.samples=s.samples,n._tk.format=s.format,n._tk.info=s.info,n._tk.nochr=s.nochr}catch(t){console.log("missing file ignored:",s.file)}}}if(n._tk?.samples.length){if(!n._tk.format)throw"bcf file has samples but no FORMAT"}else if(n._tk.format)throw"bcf file has FORMAT but no samples";if(n._tk.format){for(const t in n._tk.format)"GT"==t&&(n._tk.format[t].isGT=!0);if(t.queries.snvindel.format4filters){if(!Array.isArray(t.queries.snvindel.format4filters))throw"snvindel.format4filters[] is not array";for(const e of t.queries.snvindel.format4filters)n._tk.format[e]&&(n._tk.format[e].isFilter=!0);delete t.queries.snvindel.format4filters}}if(n._tk.info){if(n.infoFields){for(const t of n.infoFields){if(!t.key)throw".key missing from one of snvindel.byrange.infoFields[]";t.name||(t.name=t.key);const e=n._tk.info[t.key];if(!e)throw"invalid key from one of snvindel.byrange.infoFields[]";e.categories=t.categories,e.name=t.name,e.separator=t.separator}delete n.infoFields}if(t.queries.snvindel.infoUrl){for(const e of t.queries.snvindel.infoUrl){const t=n._tk.info[e.key];if(!t)throw"invalid key from one of snvindel.infoUrl[]";t.urlBase=e.base}delete t.queries.snvindel.infoUrl}}return t.queries.snvindel.info=n._tk.info,t.queries.snvindel.format=n._tk.format,async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const r=mr(e);let s;if(n._tk.chr2files){const t=n._tk.chr2files[e.rglst[0].chr];if(!t)throw"unknown chr for chr2files";s=t.file}else s=n._tk.file||n._tk.url;const o=["query",s,"-r",e.rglst.map((t=>(n._tk.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1))).join(","),"-f","%ID\t%CHROM\t%POS\t%REF\t%ALT\t%INFO\t%FORMAT\n"],i=await(0,ar.T)(e,n._tk.samples,t);if(i){if(0==i.size)return[];o.push("-s",[...i].join(","))}e.variantFilter&&(0,nr.u)(e.variantFilter,o);const a=[];return await F.UE({isbcf:!0,args:o,dir:n._tk.dir,callback:s=>{const o=s.split("\t"),l=o[0],c=o[1],u=Number(o[2]),f=o[3],d=o[4].split(","),h=o[5],p={pos:u-1};(0,Wn.H)(n._tk,f,d,p,h,l,e.isoform);for(const s of p.mlst)e.hiddenmclass&&e.hiddenmclass.has(s.class)||gr(s,e)||p.mlst.length>1&&e.variantFilter?.lst&&yr(s,e)||(s.chr=(n._tk.nochr?"chr":"")+c,s.ssm_id=[s.chr,s.pos,s.ref,s.alt].join(Hn.dq),n._tk?.samples?.length&&(br(n,s,o,e.addFormatValues,t,i,r),!s.samples)||a.push(s))}}),a}}function mr(t){const e=t.formatFilter||{};return"format"==t.skewerRim?.type&&t.skewerRim.hiddenvalues?.size&&(e[t.skewerRim.formatKey]=t.skewerRim.hiddenvalues),Object.keys(e).length?e:void 0}function gr(t,e){if(!e.infoFilter)return!1;for(const n in e.infoFilter){const r=t.info[n];if(r)if(Array.isArray(r)){for(const t of e.infoFilter[n])if(r.includes(t))return!0}else if(e.infoFilter[n].includes(r))return!0}return!1}function yr(t,e){for(const n of e.variantFilter.lst){const e=t.info[n.tvs.term.id];if(null==e)return!0;if("integer"==n.tvs.term.type||"float"==n.tvs.term.type){const t=Number(e);if(Number.isNaN(t))return!0;const r=n.tvs.ranges?.[0];if(r){if("start"in r)if(r.startinclusive){if(t<r.start)return!0}else if(t<=r.start)return!0;if("stop"in r)if(r.stopinclusive){if(t>r.stop)return!0}else if(t>=r.stop)return!0}}}return!1}function br(t,e,n,r,s,o,i){if(!n[6]||"."==n[6])return;const a=[];for(const e of n[6].split(":")){const n=t._tk.format[e];if(!n)throw"invalid format field: "+n;a.push(n)}const l=[];let c=t._tk.samples;o&&(c=[...o].map((t=>({name:t}))));for(const[t,e]of c.entries()){const s=n[t+7];if(!s||"."==s)continue;const o=vr(s.split(":"),a,e,r);if(o){if(i){let t=!1;for(const e in i){const n=e in o.formatK2v?o.formatK2v[e]:lr;if(i[e].has(n)){t=!0;break}}if(t)continue}l.push(o)}}l.length&&(e.samples=l)}function vr(t,e,n,r){const s={};for(const[n,r]of e.entries()){const e=t[n];if(e&&"."!=e)if(r.isGT){if("./."==e||".|."==e)continue;s.GT=e}else s[r.ID]=e}if(0==Object.keys(s).length)return null;const o={sample_id:n.name};return r&&(o.formatK2v=s),o}function wr(t,e,n,r=1){r=Number(r);const s=200,o=20;let i=0;for(const t in e.majorchr)i+=e.majorchr[t];const a=800/i,l={};let c=0;const u=[];for(const t in e.majorchr){const n=e.majorchr[t];l[t]=(0,Fn.Z)().domain([0,n]).range([a*c,a*(c+n)]),c+=n,u.push({chr:t,chrLen:n,xStart:a*(c-n),xStop:a*c})}const f=(0,Fn.Z)().domain([n.min,n.max]).range([s,0]),d=(0,S.createCanvas)(890*r,240*r),h=d.getContext("2d");r>1&&h.scale(r,r),g(n.max),g(0),g(n.min);const p=O().createInterface({input:m().createReadStream(t)});return new Promise(((t,r)=>{p.on("line",(t=>{const e=t.split("\t"),r=e[0];if(!r)return;if(!l[r])return;const s=Number(e[1]);if(!Number.isInteger(s))return;const i=Number(e[2]);if(!Number.isFinite(i))return;if(i<n.min||i>n.max)return;h.fillStyle=i>0?n.positiveColor:n.negativeColor;const a=l[r](s),c=o+f(i);h.fillRect(70+a,c,1,1)})),p.on("close",(()=>{!function(){h.strokeStyle="black",h.beginPath();{const t=220-f(0);h.moveTo(70,t),h.lineTo(870,t),h.stroke()}let t=!0;h.fillStyle="black",h.font="12px Arial",h.textAlign="center";for(const n in l){if(h.fillText(n.replace("chr",""),70+l[n](e.majorchr[n]/2),234),t){t=!1;continue}const r=Math.floor(70+l[n](0))+.5;h.moveTo(r,o),h.lineTo(r,220),h.stroke()}h.closePath()}(),t({src:d.toDataURL(),canvasWidth:890,canvasHeight:240,xoff:70,chrLst:u})}))}));function g(t){h.fillStyle="black",h.font="12px Arial",h.textAlign="right";const e=o+f(t);h.fillText(t,64,e+5),h.strokeStyle="black",h.beginPath(),h.moveTo(66,e),h.lineTo(70,e),h.stroke(),h.closePath()}}function _r(t,e,n,r,s,o){for(const i of e.yesSamples){if(o&&!o.has(i))continue;n.has(i)||n.set(i,{sample:i});const e=n.get(i);r in e||(e[r]={key:r,values:[],label:r}),s?e[r].values.some((e=>e.dt==t&&e.origin==s))||e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:i,origin:s}):e[r].values.some((e=>e.dt==t))||e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:i})}for(const i of e.noSamples){if(o&&!o.has(i))continue;n.has(i)||n.set(i,{sample:i});const e=n.get(i);r in e||(e[r]={key:r,values:[],label:r}),s?e[r].values.some((e=>e.dt==t&&e.origin==s))||e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:i,origin:s}):e[r].values.some((e=>e.dt==t))||e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:i})}}async function xr(t,e){if(t.chr&&Number.isInteger(t.start)&&Number.isInteger(t.stop))return;if(!t.name)throw"both term.name and term.chr/start/stop missing";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)throw"unknown gene name";const r=n.find((t=>t.isdefault))||n[0],s=JSON.parse(r.genemodel);if(!s.chr||!Number.isInteger(s.start)||!Number.isInteger(s.stop))throw"invalid chr/start/stop from returned gm";return t.chr=s.chr,t.start=s.start,t.stop=s.stop,s.isoform}async function kr(t,e,n,r){const s={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,sessionid:r.sessionid,gdcUseCaseuuid:!0};if(t.queries.snvindel.byisoform)return await async function(t,e){if(t.isoform&&"string"==typeof t.isoform)return;if(!t.name)throw"both term.name and term.isoform";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)return;const r=n.find((t=>t.isdefault))||n[0],s=JSON.parse(r.genemodel);if(!s.isoform)throw"isoform missing from returned gm";t.isoform=s.isoform}(e,n),e.isoform?(s.isoform=e.isoform,await t.queries.snvindel.byisoform.get(s)):[];if(t.queries.snvindel.byrange)return s.isoform=await xr(e,n),s.rglst=[e],await t.queries.snvindel.byrange.get(s);throw"unknown queries.snvindel method"}function qr(t,e){e.yesSamples=new Set,e.noSamples=new Set;const n=`SELECT sample, value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = '${e.term_id}'`,r=t.cohort.db.connection.prepare(n).all();for(const t of r)e.yes.value.includes(t.value)?e.yesSamples.add(t.sample):e.no.value.includes(t.value)&&e.noSamples.add(t.sample)}function Nr(t,e,n){if(e.skewerRim){if("format"!=e.skewerRim.type)throw"unknown skewerRim.type";t.rim1count=0;for(const n of t.samples)n.formatK2v?.[e.skewerRim.formatKey]==e.skewerRim.rim1value&&t.rim1count++}}function Sr(t,e){if(e.queries.snvindel?.format)for(const n in e.queries.snvindel.format)if(e.queries.snvindel.format[n].isFilter){t.formatK2count||(t.formatK2count={}),t.formatK2count[n]||(t.formatK2count[n]={v2c:{},unannotatedCount:0});for(const e of t.samples){const r=e.formatK2v?.[n];null==r?t.formatK2count[n].unannotatedCount++:t.formatK2count[n].v2c[r]=1+(t.formatK2count[n].v2c[r]||0)}}}function Ar(t,e){if(t.startunbounded){if(t.stopunbounded)throw"both start & stop are unbounded from "+e;if(!Number.isFinite(t.stop))throw".stop undefined when start is unbounded from "+e}else if(t.stopunbounded){if(!Number.isFinite(t.start))throw".start undefined when stop is unbounded from "+e}else{if(!Number.isFinite(t.start))throw".start undefined when start is not unbounded from "+e;if(!Number.isFinite(t.stop))throw".stop undefined when stop is not unbounded from "+e;if(t.start>=t.stop)throw".start is not lower than stop from "+e}}const Mr="Ancestry_PC_";async function Tr(t,e=null,r=null){if(!t.cohort.termdb)throw"cohort.termdb missing when cohort.db is used";await async function(t){if(t.phewas){if(t.phewas.samplefilter4termtype&&t.phewas.samplefilter4termtype.condition&&!t.phewas.samplefilter4termtype.condition.filter)throw"filter{} missing from tdb.phewas.samplefilter4termtype.condition";if(t.phewas.comparison_groups){if(!Array.isArray(t.phewas.comparison_groups))throw"tdb.phewas.comparison_groups is not array";if(0==t.phewas.comparison_groups.length)throw"tdb.phewas.comparison_groups[] cannot be empty"}}if(t.selectCohort){if(!t.selectCohort.term)throw"term{} missing from termdb.selectCohort";if(!t.selectCohort.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof t.selectCohort.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=t.selectCohort.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';if(!t.selectCohort.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(t.selectCohort.values))throw"termdb.selectCohort.values is not array";if(0==t.selectCohort.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const e of t.selectCohort.values){if(!e.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(e.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==e.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}if(t.restrictAncestries){if(!Array.isArray(t.restrictAncestries)||0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCfile)e.pcs=await jr(e.PCfile,e.PCcount);else if(e.PCfileBySubcohort)for(const t in e.PCfileBySubcohort){const n=e.PCfileBySubcohort[t];if(!n.file)throw".file missing for a subcohort in PCfileBySubcohort";n.pcs=await jr(n.file,e.PCcount)}}}}(t.cohort.termdb),await async function(t){if("scatterplots"in t)for(const e of t.scatterplots.plots){const t=y().join(s().tpmasterdir,e.file);await F.Ic(t)}}(t.cohort),(0,Kn.JV)(t),function(t){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT * FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[r]=t.sampleId2Name.get(+r);return n}}(t);const{mayGetGeneVariantData:o,getTermTypes:i,mayGetMatchingGeneNames:a}=n(7833);t.mayGetGeneVariantData=o,t.getTermTypes=i,t.mayGetMatchingGeneNames=a,t.cohort?.db?.refresh&&e&&Qn(t,e,r)}async function Cr(t,e){if(!t.track)throw"no mds2 track; missing ds.track{}";const n=t.track;n.name||(n.name=t.label),function(t){if(!t.populations)return;if(!Array.isArray(t.populations))throw"populations should be array";for(const e of t.populations){if(!e.key)throw"key missing from a population";if(e.label||(e.label=e.key),!Array.isArray(e.sets))throw".sets is not an array in population: "+e.key;for(const t of e.sets){if(!t.infokey_AC)throw"infokey_AC missing from a set of population: "+e.key;if(!t.infokey_AN)throw"infokey_AN missing from a set of population: "+e.key;if(e.termfilter&&!t.termfilter_value)throw"termfilter_value missing from a set of population where termfilter is set: "+e.key}}}(n),await async function(t,e,n){if(!t)return;if(!t.chr2bcffile)throw"vcftk.chr2bcffile is missing";{if("object"!=typeof t.chr2bcffile)throw"chr2bcffile not an object";for(const e in t.chr2bcffile)t.chr2bcffile[e]=y().join(s().tpmasterdir,t.chr2bcffile[e]);const n={file:t.chr2bcffile[e.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await F._H(n,e,!0),t.info=n.info,t.format=n.format,t.samples=n.samples,t.nochr=n.nochr}if(t.AD&&t.AD.chr2bcffile){if("object"!=typeof t.AD.chr2bcffile)throw"AD.chr2bcffile not an object";for(const e in t.AD.chr2bcffile)t.AD.chr2bcffile[e]=y().join(s().tpmasterdir,t.AD.chr2bcffile[e]);const r={file:t.AD.chr2bcffile[e.defaultcoord.chr]};if(!r.file)throw"default chr missing from AD.chr2bcffile";await F._H(r,e,!0),t.AD.info=r.info,t.AD.format=r.format,t.AD.samples=r.samples,t.AD.nochr=r.nochr,console.log(n.label+" vcf: AD: "+t.AD.samples.length+" samples");for(const e of t.AD.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}}if(t.samples){for(const e of t.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}console.log(n.label+" vcf: "+t.samples.length+" samples")}else console.log(n.label+" vcf: no samples");if(t.numerical_axis&&t.numerical_axis.info_keys){if(!Array.isArray(t.numerical_axis.info_keys))throw"numerical_axis.info_keys should be an array";for(const e of t.numerical_axis.info_keys){const n=t.info[e.key];if(!n)throw'INFO field "'+e.key+'" not found for numerical_axis';if("Float"!=n.Type&&"Integer"!=n.Type)throw'INFO field "'+e.key+'" from numerical_axis not of integer or float type';if("1"!=n.Number&&"A"!=n.Number)throw'for numerical axis, INFO field "'+e.key+'" only allows to be Number=1 or Number=A'}}if(t.plot_mafcov){if(!t.AD)throw".plot_mafcov enabled but .AD{} missing from vcf";if(!t.AD.samples)throw".plot_mafcov enabled but no samples from vcf";if(!t.AD.format)throw".plot_mafcov enabled but no FORMAT fields from vcf";if(!t.AD.format.AD)throw".plot_mafcov enabled but the AD FORMAT field is missing";if("R"!=t.AD.format.AD.Number)throw"AD FORMAT field Number=R is not true";if("Integer"!=t.AD.format.AD.Type)throw"AD FORMAT field Type=Integer is not true";if(t.plot_mafcov.overlay_term){if(!n.cohort)throw"ds.cohort missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb)throw"ds.cohort.termdb missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb.q)throw"ERR: termdb.q{} missing while trying to access termdb helper functions";if(!n.cohort.termdb.q.termjsonByOneid)throw"ERR: q.termjsonByOneid missing";const e=n.cohort.termdb.q.termjsonByOneid(t.plot_mafcov.overlay_term);if(!e)throw'unknown term id "'+t.plot_mafcov.overlay_term+'" from vcftk.plot_mafcov.overlay_term';t.plot_mafcov.overlay_term=e}}if(t.termdb_bygenotype){if(!t.samples)throw".termdb_bygenotype enabled but no samples from vcf";if(!t.format)throw".termdb_bygenotype enabled but no FORMAT fields from vcf";if(!t.format.GT)throw".termdb_bygenotype enabled but the GT FORMAT field is missing";if(!n.cohort)throw"termdb_bygenotype but ds.cohort missing";if(!n.cohort.termdb)throw"termdb_bygenotype but ds.cohort.termdb missing";if(t.termdb_bygenotype.getAF){if(!t.termdb_bygenotype.termid_sex)throw"termid_sex missing for getAF at termdb_bygenotype";if(!t.termdb_bygenotype.value_male)throw"value_male missing for getAF at termdb_bygenotype";const e=n.cohort.termdb.q.getSample2value(t.termdb_bygenotype.termid_sex);t.termdb_bygenotype.male_samples=new Set;for(const n of e)n.value==t.termdb_bygenotype.value_male&&t.termdb_bygenotype.male_samples.add(n.sample);if(!t.termdb_bygenotype.sex_chrs)throw"sex_chrs missing for getAF at termdb_bygenotype";if(!Array.isArray(t.termdb_bygenotype.sex_chrs))throw"sex_chrs is not array";t.termdb_bygenotype.sex_chrs=new Set(t.termdb_bygenotype.sex_chrs)}}if(t.samples){t.sample2arrayidx=new Map;for(const[e,n]of t.samples.entries())t.sample2arrayidx.set(n.name,e)}}(n.vcf,e,t),function(t){if(!t.info_fields)return;if(!Array.isArray(t.info_fields))throw"tk.info_fields is not array";for(const e of t.info_fields){if(!e.key)throw".key missing from one of tk.info_fields[]";if(t.vcf&&t.vcf.info&&!t.vcf.info[e.key])throw`info field ${e.key} missing from tk.vcf.info{}`;if(e.label||(e.label=e.key),e.iscategorical){if(!Array.isArray(e.values))throw".values[] not an array of categorical INFO field: "+e.key;for(const t of e.values){if(!t.key)throw"key missing from a value of categorical INFO: "+e.key;t.label||(t.label=t.key)}}else if(e.isfloat||e.isinteger){if(!e.range)throw".range{} missing from a numerical INFO: "+e.key;Ar(e.range,"tk.info_fields[]")}else if(!e.isflag)throw"tk.info_fields unknown type: "+e.key}}(n),await async function(t,e,n){if(!t)return;if(!Array.isArray(t.tracks))throw"ld.tracks[] not an array";if(0==t.tracks.length)throw"ld.tracks[] is empty array";for(const n of t.tracks){if(!n.name)throw".name missing from a ld track";if(!Number.isInteger(n.viewrangelimit))throw'viewrangelimit missing from ld track "'+n.name+'"';if(n.file)n.file.startsWith(s().tpmasterdir)||(n.file=y().join(s().tpmasterdir,n.file)),await F.LC(n.file),n.nochr=await F.Jy(n.file,null,e),console.log(n.file+": "+(n.nochr?"no chr":"has chr"));else if(!n.chr2file)throw"ld tk has no file or chr2file"}}(n.ld,e),await async function(t,e){if(!t)return}(n.svcnv,0),function(t){const e=new Set;if(t.vcf&&t.vcf.samples)for(const n of t.vcf.samples)e.add(n.name);t.svcnv;e.size&&(t.samples=[...e])}(n),n.samples&&console.log(t.label+": mds2: "+n.samples.length+" samples")}async function jr(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(Mr+t,new Map);let r=0;for(const o of(await F.b5(y().join(s().tpmasterdir,t))).trim().split("\n")){r++;const t=o.split("\t"),s=Number(t[0]);if(!Number.isInteger(s))throw"non-integer sample id from a line of restrictAncestries pc file";for(let r=1;r<=e;r++){const e=Mr+r,o=Number(t[r]);if(Number.isNaN(o))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(s,o)}}return console.log(r,"samples loaded from "+t),Object.freeze(n)}var Er=n(9157);const Or=n(334),Ir="%CHROM\t%POS\t%ID\t%REF\t%ALT\t%QUAL\t%FILTER\t%INFO";async function Rr(t,e,n,r){if(!t.rglst)throw".rglst[] missing";const s=n.track.vcf;if(!s)throw"ds.track.vcf missing";const o={info:s.info,format:s.format,samples:s.samples};await async function(t,e,n){if(t.querymode={},t.AFtest){if(n.iscustom)throw"custom track does not support AFtest";for(const e of t.AFtest.groups)if(!e.is_infofield)if(e.is_termdb)e.columnidx=await Fr(e.filter,n);else{if(!e.is_population)throw"Cannot set query mode: unknown group type";{if(!n.track.populations)throw"ds.track.populations missing";const r=n.track.populations.find((t=>t.key==e.key));if(!r)throw"unknown population key: "+e.key;if(e.population=JSON.parse(JSON.stringify(r)),t.AFtest.termfilter&&t.AFtest.termfilter[0].term.id==e.population.termfilter){const n=e.population.sets.find((e=>e.termfilter_value==t.AFtest.termfilter[0].values[0].key));if(!n)throw"no matching set found for a termfilter from a population";e.population.sets=[n]}}}if(t.AFtest.testby_fisher&&t.AFtest.groups.find((t=>t.is_infofield)))throw"cannot do fisher test for an INFO field";{const e=t.AFtest.groups.find((t=>t.is_population));if(e&&e.adjust_race){const r=t.AFtest.groups.find((t=>t.is_termdb));if(!r)throw"cannot adjust race: termdb group missing";r.pop2average=await async function(t,e,n,r){const s=new Map;let o=0;for(const e of t){const t={infokey_AC:e.infokey_AC,infokey_AN:e.infokey_AN,average:0},r=await Yn.J4({ds:n,key:e.key});for(const e of r){if(!n.track.vcf.sample2arrayidx.has(e.sample))continue;const r=Number(e.value);Number.isFinite(r)&&(t.average+=r,o+=r)}s.set(e.key,t)}for(const[t,e]of s)e.average/=o;return s}(e.population.sets,r.columnidx,n)}}return void(t.querymode.range_AFtest=!0)}t.querymode.range_variantonly=!0}(t,0,n),function(t,e){if(e.querymode.range_variantonly||e.querymode.range_AFtest){delete t.samples;for(const t of e.rglst)t.variants=[]}e.bcfformat=Ir,e.exportgenotype||e.querymode.range_AFtest?e.bcfformat+="\t%FORMAT\n":e.querymode.range_variantonly&&(e.querymode.slicecolumnindex||(e.bcfformat+="\\n"))}(o,t),t.exportgenotype&&(r.mlst=[]),function(t,e){const n=(r=t.rglst[0],r.usegm_isoform?{gmmode:"protein",usegm:{isoform:r.usegm_isoform}}:{});var r;t.m_is_filtered=r=>{let s=!1;if(t.info_fields)for(const n of t.info_fields){const t=e.info_fields[n.key];let o;if(r.info&&(o=r.info[n.key]),null==o&&r.altinfo&&(o=r.altinfo[n.key]),n.iscategorical)null==o?(t.unannotated_count=1+(t.unannotated_count||0),n.unannotated_ishidden&&(s=!0)):(t.value2count[o]=1+(t.value2count[o]||0),n.hiddenvalues[o]&&(s=!0));else if(n.isnumerical)null==o&&null!=n.missing_value&&(o=n.missing_value),n.range.startunbounded||(n.range.startinclusive?o<n.range.start&&(s=!0):o<=n.range.start&&(s=!0)),n.range.stopunbounded||(n.range.stopinclusive?o>n.range.stop&&(s=!0):o>=n.range.stop&&(s=!0)),s&&t.filteredcount++;else{if(!n.isflag)throw"unknown info type";o?t.count_yes++:t.count_no++,(n.remove_yes&&o||n.remove_no&&!o)&&(s=!0)}}return!!s||(P.vcfcopymclass(r,n),e.mclass2count[r.class]=(e.mclass2count[r.class]||0)+1,t.hidden_mclass&&t.hidden_mclass.has(r.class)&&(s=!0),s)}}(t,r);for(const e of t.rglst){if(s.viewrangeupperlimit&&e.stop-e.start>=s.viewrangeupperlimit){e.rangetoobig="Zoom in under "+P.bplen(s.viewrangeupperlimit)+" to view VCF data";continue}const n=(s.nochr?e.chr.replace("chr",""):e.chr)+":"+e.start+"-"+e.stop,r=s.chr2bcffile[e.chr];if(!r)throw"chr not found in chr2bcffile";await F.UE({isbcf:!0,args:["query",r,"-r",n,"-f",t.bcfformat],dir:s.dir,callback:i(e)})}function i(e){return n=>{if(t.exportgenotype){const e=n.split("\t"),[s,i,a]=D.S(e.slice(0,8).join("\t"),o);for(const n of i){if(t.m_is_filtered(n))continue;const s=[n.chr+"."+(n.pos+1)+"."+n.ref+"."+n.alt,n.name||""];for(let t=9;t<e.length;t++){const r=e[t].split(":",1)[0];if("."==r){s.push(".");continue}const o=r.split(-1==r.indexOf("/")?"|":"/");s.push(("0"==o[0]?n.ref:n.alt)+("0"==o[1]?n.ref:n.alt))}r.mlst.push(s.join("\t"))}return}let i;if(t.querymode.range_variantonly)if(t.querymode.slicecolumnindex);else{const[e,r,s]=D.S(n,o);i=[];for(const e of r)t.m_is_filtered(e)||i.push(e)}else t.querymode.range_AFtest&&(i=function(t,e,n,r){const s=t.split("\t"),[o,i,a]=D.S(s.slice(0,8).join("\t"),n),l=i.filter((t=>!e.m_is_filtered(t)));if(0==l.length)return;const c=[s[3],...s[4].split(",")],u=[];for(const t of l){const n=Dr(s,t,c,e);if(Pr(n)){if(u.push(t),e.AFtest.testby_AFdiff){for(const t of n)if(t.is_infofield)t.v=t.infofieldvalue;else{if(!t.is_termdb&&!t.is_population)throw"unknown group type";t.v=t.altcount/(t.refcount+t.altcount)}t.AFtest_group_values=[n[0].v,n[1].v],t.nm_axis_value=n[0].v-n[1].v}else e.AFtest.testby_fisher&&(t.contigencytable=[n[0].altcount,n[0].refcount,n[1].altcount,n[1].refcount]);{const r=e.AFtest.groups.find((t=>t.is_population));if(r&&r.adjust_race){const e=n.find((t=>t.is_population));t.popsetadjvalue=[];for(const[n,r]of e.set2value)t.popsetadjvalue.push([n,r.ACraw,r.ANraw-r.ACraw,Number.parseInt(r.ACadj),Number.parseInt(r.ANadj-r.ACadj)])}}}}return u}(n,t,o));if(i)for(const t of i)t.csq&&(t.csq_count=t.csq.length,delete t.csq),delete t._m,delete t.vcf_ID,delete t.sampledata,s.nochr&&(t.chr="chr"+t.chr),e.variants.push(t)}}await async function(t){if(!t.querymode.range_AFtest)return;if(!t.AFtest.testby_fisher)return;const e=[],n={};for(const r of t.rglst)if(r.variants)for(const t of r.variants)if(t.contigencytable){const r=t.chr+"."+t.pos+"."+t.ref+"."+t.alt;e.push(r+"\t"+t.contigencytable.join("\t")),n[r]=t}if(0==e.length)return;const r=await Er(y().join(Or.binpath,"/utils/fisher.R"),e);for(const t of r){const e=t.split("\t"),r=n[e[0]];if(r){const t=Number.parseFloat(e[5]);r.AFtest_pvalue=t,r.nm_axis_value=Number.isNaN(t)?0:-Math.log10(t)}}}(t),function(t,e,n,r){if(e.exportgenotype)return t.exportgenotype="variant\tSNP\t"+n.samples.map((t=>r.cohort.termdb.id2sampleName(t.name))).join("\t")+"\n"+t.mlst.join("\n"),void delete t.mlst;t.vcf={rglst:[]};for(const n of e.rglst){const e={chr:n.chr,start:n.start,stop:n.stop,width:n.width,reverse:n.reverse,xoff:n.xoff};t.vcf.rglst.push(e),n.rangetoobig?(e.rangetoobig=n.rangetoobig,delete n.rangetoobig):n.variants?(e.variants=n.variants,delete n.variants):n.canvas&&(e.img=n.canvas.toDataURL(),delete n.canvas)}if(e.AFtest&&e.AFtest.groups.find((t=>t.is_termdb))){t.AFtest_termdbgroup=[];let n=e.AFtest.groups[0];if(n.is_termdb&&(t.AFtest_termdbgroup[0]={samplecount:n.columnidx.length},n.pop2average)){t.AFtest_termdbgroup[0].popsetaverage=[];for(const[e,r]of n.pop2average)t.AFtest_termdbgroup[0].popsetaverage.push([e,r.average])}if(n=e.AFtest.groups[1],n.is_termdb&&(t.AFtest_termdbgroup[1]={samplecount:n.columnidx.length},n.pop2average)){t.AFtest_termdbgroup[1].popsetaverage=[];for(const[e,r]of n.pop2average)t.AFtest_termdbgroup[1].popsetaverage.push([e,r.average])}}}(r,t,s,n)}async function Fr(t,e){if(!e.track)throw"ds.track{} missing";return(await Yn.cf(t,e)).reduce(((t,n)=>{const r=e.track.vcf.sample2arrayidx.get(n);return r>=0&&t.push(r),t}),[])}function Pr(t){if(t.find((t=>t.is_infofield)))return!0;return t[0].altcount+t[1].altcount>0}function Dr(t,e,n,r){return r.AFtest.groups.reduce(((s,o)=>{if(o.is_infofield)s.push({is_infofield:!0,infofieldvalue:Lr(e,o)});else if(o.is_termdb){const r=function(t,e,n){let r=!0;const s=new Map;for(const e of t)s.set(e,0);for(const o of n){if(!e[9+o])continue;const n=e[9+o].split(":")[0];"."!=n&&n.split(-1==n.indexOf("/")?"|":"/").forEach((e=>{const n=Number.parseInt(e);if(Number.isNaN(n))return;const 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n}if(t.altinfo){const n=t.altinfo[e.key];if(null!=n)return n}return e.missing_value}var $r=n(5540),zr=n(7763);const Zr="#aaa",Ur="%CHROM\t%POS\t%ID\t%REF\t%ALT\t%QUAL\t%FILTER\t%INFO\t%FORMAT\n";async function Br(t,e,n,r,s){const o=r.track.ld.tracks.find((e=>e.name==t.name));if(!o)throw"ld track not found by name: "+t.name;if(!e.rglst)throw"rglst missing";s.ld[o.name]={rglst:[]};const i=e.trigger_ld.connheight||50;for(const t of e.rglst){const e={chr:t.chr,start:t.start,stop:t.stop,width:t.width,reverse:t.reverse,xoff:t.xoff};if(s.ld[o.name].rglst.push(e),t.stop-t.start>=o.viewrangelimit){e.rangetoobig="Zoom in under "+(0,P.bplen)(o.viewrangelimit)+" to view LD data";continue}const n=[],r=new Set,a=(o.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop;await F.UE({args:[o.file,a],dir:o.dir,callback:e=>{const o=e.split("\t"),i=Number.parseInt(o[1]);if(i<t.start)return;const 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t.filter((t=>l.has(t.name)))}async function ss(t,e,n,r){const o=n.samplerule.set,i=t.url?await F.d1(t.url,t.indexURL):null,a=new Set,l=new Set,c=new Set;return await F.UE({args:[t.file?y().join(s().tpmasterdir,t.file):t.url,(t.nochr?o.chr.replace("chr",""):o.chr)+":"+o.start+"-"+(o.stop+1)],dir:i,callback:t=>{const n=t.split("\t"),s=Number.parseInt(n[1]),i=Number.parseInt(n[2]),u=JSON.parse(n[3]);if(e.has(u.sample)){if(u.dt==P.dtcnv){if(!o.cnv)return;if(o.cnv.focalsizelimit&&i-s>=o.cnv.focalsizelimit)return;if(o.cnv.valuecutoff&&Math.abs(u.value)<o.cnv.valuecutoff)return;return r?u.value>0?a.add(u.sample):l.add(u.sample):c.add(u.sample),void o.samples_cnv.add(u.sample)}if(u.dt==P.dtloh){if(!o.loh)return;if(o.loh.focalsizelimit&&i-s>=o.loh.focalsizelimit)return;if(o.loh.valuecutoff&&u.segmean<o.loh.valuecutoff)return;return c.add(u.sample),void o.samples_loh.add(u.sample)}if(u.dt==P.dtsv){if(!o.sv)return;return c.add(u.sample),void o.samples_sv.add(u.sample)}if(u.dt==P.dtfusionrna){if(!o.fusion)return;return c.add(u.sample),void o.samples_fusion.add(u.sample)}if(u.dt==P.dtitd){if(!o.itd)return;return c.add(u.sample),void o.samples_itd.add(u.sample)}}}}),r?[a,l]:c}async function os(t,e,n,r,o){const i=o.samplerule.set,a=e.url?await F.d1(e.url,e.indexURL):null;await F.UE({args:[e.file?y().join(s().tpmasterdir,e.file):e.url,(e.nochr?i.chr.replace("chr",""):i.chr)+":"+i.start+"-"+(i.stop+1)],dir:a,callback:s=>{if(e.type==P.mdsvcftype.vcf){const[o,a,l]=D.S(s,{nochr:e.nochr,samples:e.samples,info:t.info,format:e.format});for(const t of a)if(t.sampledata&&!(i.snvindel.ref&&(t.ref!=i.snvindel.ref||t.alt!=i.snvindel.alt)||i.snvindel.hiddenclass&&(P.vcfcopymclass(t,{}),i.snvindel.hiddenclass[t.class])))for(const e of t.sampledata)n.has(e.sampleobj.name)&&(r.add(e.sampleobj.name),i.samples_snvindel.add(e.sampleobj.name))}}})}async function is(t,e,n){if(!n.queries)throw".queries{} missing from ds";let r;for(const t in n.queries)n.queries[t].isgenenumeric&&(r=n.queries[t]);if(!r)throw"no gene numeric query from ds";const o=r.url?await F.d1(r.url,r.indexURL):null,i=e.samplerule.set,a=new Map;await F.UE({args:[r.file?y().join(s().tpmasterdir,r.file):r.url,i.chr+":"+i.start+"-"+i.stop],dir:o,callback:t=>{const e=JSON.parse(t.split("\t")[3]);e.sample&&Number.isFinite(e.value)&&e.gene==i.gene&&a.set(e.sample,e.value)}});const l=[];for(const e of t)a.has(e.name)&&(e.genevalue=a.get(e.name),l.push(e));return l.sort(((t,e)=>t.genevalue-e.genevalue)),[r,l]}function as(t){t.lst.sort(((t,e)=>t.serialtime-e.serialtime));let e=t.lst.length,n=[],r=0;t.steps=[];for(const s of t.lst){if(0==s.censored){n.push(s.serialtime);continue}const o=1*(1-r)/(e-n.length);t.steps.push({x:s.serialtime,y:r,drop:o,censored:n}),r+=o,e-=n.length+1,n=[]}n.length>0&&t.steps.push({x:t.lst[t.lst.length-1].serialtime,y:r,drop:0,censored:n})}exports.do_plot=as;const ls={};function cs(t,e,n){const r=+new Date;if(t.ip in 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e=bs[t],n={species:e.species,name:t,hasSNP:!!e.snp,hasIdeogram:e.genedb.hasIdeogram,fimo_motif:!!e.fimo_motif,blat:!!e.blat,geneset:e.geneset,defaultcoord:e.defaultcoord,isdefault:e.isdefault,majorchr:e.majorchr,majorchrorder:e.majorchrorder,minorchr:e.minorchr,tracks:e.tracks,hicenzymefragment:e.hicenzymefragment,datasets:{}};if(e.termdbs){n.termdbs={};for(const t in e.termdbs)n.termdbs[t]={label:e.termdbs[t].label}}for(const t in e.datasets){const r=e.datasets[t];r.isMds3?n.datasets[r.label]={isMds3:!0,noHandleOnClient:r.noHandleOnClient,label:r.label}:r.isMds?n.datasets[r.label]={isMds:!0,mdsIsUninitiated:!0,noHandleOnClient:r.noHandleOnClient,label:r.label}:n.datasets[r.label]={isofficial:!0,legacyDsIsUninitiated:!0,noHandleOnClient:r.noHandleOnClient,label:r.label}}if(e.hicdomain){n.hicdomain={groups:{}};for(const t in e.hicdomain.groups){const r=e.hicdomain.groups[t];n.hicdomain.groups[t]={name:r.name,reference:r.reference,sets:{}};for(const e in 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e={isMds:!0,noHandleOnClient:t.noHandleOnClient,label:t.label,version:t.version,annotationsampleset2matrix:t.annotationsampleset2matrix,mutationAttribute:t.mutationAttribute,locusAttribute:t.locusAttribute,alleleAttribute:t.alleleAttribute,hide_genotypedownload:t.hide_genotypedownload,hide_phewas:t.hide_phewas,sample2bam:t.sample2bam};if(t.queries&&(e.queries={}),t.track&&(e.track=function(t){const e=t.track,n={name:e.name,info_fields:e.info_fields,sample_termfilter:e.sample_termfilter};return e.vcf&&(n.vcf={numerical_axis:e.vcf.numerical_axis,format:e.vcf.format,info:e.vcf.info,check_pecanpie:e.vcf.check_pecanpie},e.vcf.plot_mafcov&&(n.vcf.plot_mafcov={},t.cohort&&t.cohort.termdb&&(n.vcf.plot_mafcov.overlay_term=e.vcf.plot_mafcov.overlay_term||{})),e.vcf.termdb_bygenotype&&(n.vcf.termdb_bygenotype=!0),e.populations&&(n.populations=e.populations)),e.ld&&(n.ld={tracks:e.ld.tracks.map((t=>({name:t.name,shown:t.shown}))),overlay:e.ld.overlay}),n}(t)),t.singlesamplemutationjson&&(e.singlesamplemutationjson=1),t.gene2mutcount&&(e.gene2mutcount=!0,e.mutCountType=t.gene2mutcount.mutationTypes),t.assayAvailability&&(e.assayAvailability=1),t.cohort&&t.cohort.sampleAttribute){const n={};for(const e in t.cohort.sampleAttribute.attributes){const r=t.cohort.sampleAttribute.attributes[e];r.clientnoshow||(n[e]=r)}e.sampleAttribute={attributes:n}}if(t.cohort){if(t.cohort.termdb&&(e.termdb={selectCohort:t.cohort.termdb.selectCohort}),t.cohort.attributes&&t.cohort.attributes.defaulthidden&&(e.cohortHiddenAttr=t.cohort.attributes.defaulthidden),t.cohort.survivalplot){e.survivalplot={samplegroupattrlst:t.cohort.survivalplot.samplegroupattrlst,plots:[]};for(const n in t.cohort.survivalplot.plots){const r=t.cohort.survivalplot.plots[n];e.survivalplot.plots.push({key:n,name:r.name,timelabel:r.timelabel})}}if(t.cohort.mutation_signature){const n={};for(const e in t.cohort.mutation_signature.sets){const r=t.cohort.mutation_signature.sets[e];n[e]={name:r.name,signatures:r.signatures}}e.mutation_signature={sets:n}}}for(const n in t.queries){const r=t.queries[n],s={name:r.name,hideforthemoment:r.hideforthemoment};if(r.istrack){if(s.istrack=!0,s.type=r.type,s.isfull=r.isfull,null!=r.nochr&&(s.nochr=r.nochr),r.infoFilter&&(s.infoFilter=r.infoFilter),r.readcountCutoff&&(s.readcountCutoff=r.readcountCutoff),r.valueLabel&&(s.valueLabel=r.valueLabel),r.valueCutoff&&(s.valueCutoff=r.valueCutoff),r.bplengthUpperLimit&&(s.bplengthUpperLimit=r.bplengthUpperLimit),r.segmeanValueCutoff&&(s.segmeanValueCutoff=r.segmeanValueCutoff),r.lohLengthUpperLimit&&(s.lohLengthUpperLimit=r.lohLengthUpperLimit),r.type==P.tkt.mdssvcnv){if(r.groupsamplebyattr&&(s.groupsamplebyattr=r.groupsamplebyattr),s.multihidelabel_fusion=r.multihidelabel_fusion,s.multihidelabel_sv=r.multihidelabel_sv,s.multihidelabel_vcf=r.multihidelabel_vcf,s.showfullmode=r.showfullmode,s.legend_vorigin=r.legend_vorigin,s.no_loh=r.no_loh,r.expressionrank_querykey){const e=t.queries[r.expressionrank_querykey];if(s.checkexpressionrank={querykey:r.expressionrank_querykey,datatype:e.datatype},e.boxplotbysamplegroup&&e.boxplotbysamplegroup.additionals){const t=[];e.boxplotbysamplegroup.attributes&&t.push(e.boxplotbysamplegroup.attributes.map((t=>t.label)).join(", "));for(const n of e.boxplotbysamplegroup.additionals)t.push(n.label);s.checkexpressionrank.boxplotgroupers=t}}if(r.vcf_querykey){s.checkvcf={querykey:r.vcf_querykey,info:t.queries[r.vcf_querykey].info,format:{}};for(const e of t.queries[r.vcf_querykey].tracks)if(e.format)for(const t in e.format)s.checkvcf.format[t]=e.format[t]}}}else{if(!r.isgenenumeric)continue;s.isgenenumeric=!0,s.datatype=r.datatype,s.no_ase=r.no_ase}e.queries[n]=s}return e}async function js(t,e){if(!e)throw"invalid genome";if(!e.snp)throw"snp is not configured for this genome";const n=[];if(t.byCoord){if(e.genomicNameRegexp.test(t.chr))throw"invalid chr name";if(!Array.isArray(t.ranges))throw"ranges not an array";for(const r of t.ranges){if(!Number.isInteger(r.start)||!Number.isInteger(r.stop)||r.start<0||r.stop<r.start)throw"invalid start/stop";if(r.stop-r.start>=100)throw"range too big";const s=await F.z5(e.snp.bigbedfile,t.chr,r.start,r.stop);for(const e of s){const r=Es(e);if(t.alleleLst){let e=!1;for(const n of t.alleleLst)if(n&&!r.alleles.includes(n)){e=!0;break}if(e)continue}n.push(r)}}}else{if(!t.byName)throw"unknown query method";if(!Array.isArray(t.lst))throw".lst[] missing";for(const r of t.lst){if(e.genomicNameRegexp.test(r))continue;const t=await F.mr(e.snp.bigbedfile,r);for(const e of t){const t=Es(e);n.push(t)}}}return n}function Es(t){const e=t.split("\t"),n=e[4],r=e[6].split(",").filter(Boolean),s=n+"/"+r.join("/");return{chrom:e[0],chromStart:Number(e[1]),chromEnd:Number(e[2]),name:e[3],observed:s,alleles:[n,...r]}}function Os(t,e,n){if(n.query.isoform&&bs[n.query.genome].genomicNameRegexp.test(n.query.isoform))return;const[r,s]=e.makequery(n.query);if(!r)return;const o=t.newconn.prepare(r).all(s);let i;i=e.tidy?o.map((t=>e.tidy(t))):o;const a={};if(e.isgeneexpression){a.lst=i,a.isgeneexpression=!0,a.config=e.config;for(const e of t.queries)if(e.dsblocktracklst)for(const t of e.dsblocktracklst)t.type==P.tkt.junction&&(a.config.dsjunctiontk=t)}else a.lst=i;return a}function Is(t,e){const n=[y().join(s().tpmasterdir,t.vcffile),(t.vcf.nochr?e.query.range.chr.replace("chr",""):e.query.range.chr)+":"+e.query.range.start+"-"+e.query.range.stop];return new Promise(((e,r)=>{const s=(0,q.spawn)(vs,n),o=[],i=[];s.stdout.on("data",(t=>o.push(t))),s.stderr.on("data",(t=>i.push(t))),s.on("close",(n=>{""!=i.join("").trim()&&r("error querying vcf file");const s=o.join("").trim();e({lines:""==s?[]:s.split("\n"),vcfid:t.vcf.vcfid})}))}))}function Rs(t){if(!t.genome)return["no genome"];const e=bs[t.genome];if(!e)return["invalid genome"];if(!e.datasets)return["genome is not equipped with datasets"];if(!t.dslabel)return["dslabel missing"];const n=e.datasets[t.dslabel];if(!n)return["invalid dslabel"];if(!n.queries)return["dataset is not equipped with queries"];if(!t.querykey)return["querykey missing"];const r=n.queries[t.querykey];return r?[null,e,n,r]:["invalid querykey"]}async function Fs(t,e,n,r,o,i){const a=await async function(t,e,n,r){const o=t.checkvcf.tracks[0],i={file:o.file,url:o.url,indexURL:o.indexURL,dir:o.dir,nochr:o.nochr,samples:o.samples,info:t.checkvcf.info,format:o.format},a=await Ws(i.file?y().join(s().tpmasterdir,i.file):i.url,(i.nochr?e.replace("chr",""):e)+":"+n+"-"+r,i.dir),l=[];for(const t of a||[]){const[e,n,r]=D.S(t,i);for(const t of n)P.basecolor[t.ref]&&P.basecolor[t.alt]&&t.sampledata&&l.push(t)}return l}(o,e,n,r),l=[];for(const t in o.checkrnabam.samples){const n=o.checkrnabam.samples[t];n.hetsnps=[];for(const e of a){const r=Js(e,t,o.checkrnabam);r&&r.dnacount.ishet&&n.hetsnps.push(r)}if(n.url?n.dir=await 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n()}))}))}(r,e),m().unlink(n,(()=>{})),m().unlink(r,(()=>{}))}(l,o.checkrnabam.samples),i.checkrnabam=[];for(const n in o.checkrnabam.samples){const r=o.checkrnabam.samples[n],s=[];for(const[n,i]of t){const t={gene:n,chr:e,start:i.start,stop:i.stop},a=r.hetsnps.filter((t=>t.pos>=i.start&&t.pos<=i.stop)),l=a.filter((t=>!t.rnacount.nocoverage));if(l.length>0){const e=l.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let n=null,r=0;for(const t of l)null!=t.rnacount.pvalue&&(null==n?n=t.rnacount.pvalue:n*=t.rnacount.pvalue,t.rnacount.pvalue<=o.checkrnabam.binompvaluecutoff&&r++);null!=n&&(t.ase={markers:a.filter((t=>t.dnacount.ishet)).length,ase_markers:r,mean_delta:e/l.length,geometricmean:Math.pow(n,1/l.length)})}let c;c=r.pairedend?await Ds(r,e,i):await Ps(r,e,i),t.fpkm=1e9*c/(r.totalreads*i.exonlength),t.snps=a,s.push(t)}s.length&&i.checkrnabam.push({sample:n,genes:s})}}async function Ps(t,e,n){const r=["view","-c","-M",t.url||t.file];for(const s of n.exonunion)r.push((t.nochr?e.replace("chr",""):e)+":"+(s[0]+1)+"-"+(s[1]+1));let s;return await F.UE({isbam:!0,args:r,dir:t.dir,callback:t=>s=t}),Number.parseInt(s)}function Ds(t,e,n){return new Promise(((r,s)=>{const o=["view","-M",t.url||t.file];for(const r of n.exonunion)o.push((t.nochr?e.replace("chr",""):e)+":"+(r[0]+1)+"-"+(r[1]+1));const i=(0,q.spawn)(ws,o,{cwd:t.dir}),a=(0,q.spawn)("cut",["-f1"],{cwd:t.dir}),l=(0,q.spawn)("sort",["-u"],{cwd:t.dir}),c=(0,q.spawn)("wc",["-l"],{cwd:t.dir});i.stdout.pipe(a.stdin),a.stdout.pipe(l.stdin),l.stdout.pipe(c.stdin);const u=[],f=[];c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>f.push(t))),c.on("close",(()=>{r(Number.parseInt(u.join("")))}))}))}function Ls(t,e,n,r){const s=[];for(const r of e)r.rnacount={nocoverage:1},s.push((t.nochr?n.replace("chr",""):n)+":"+(r.pos+1)+"-"+(r.pos+1));return new Promise(((n,o)=>{const i=(0,q.spawn)(_s,["mpileup","--no-reference","-a","INFO/AD","-d",999999,"-r",s.join(","),"-q",r.rnapileup_q,"-Q",r.rnapileup_Q,t.url||t.file],{cwd:t.dir});O().createInterface({input:i.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Gs(t);if(!n)return;const r=e.find((t=>t.pos==n.pos));if(r){const t=n.allele2count[r.ref]||0,e=n.allele2count[r.alt]||0;t+e>0&&(r.rnacount={ref:t,alt:e,f:e/(t+e)})}})),i.on("close",(()=>{n()}))}))}function $s(t,e,n,r,s,o){e.hideLOHwithCNVoverlap&&zs(s);const i=[];if(o){const t=new Map;for(const[e,n]of s){const r=o.sample2group.get(e);t.has(r)||t.set(r,[]),t.get(r).push({samplename:e,items:n})}if(r)for(const e of r)if(e.dt!=P.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){const e=o.sample2group.get(n.sampleobj.name);t.has(e)||t.set(e,[]),t.get(e).find((t=>t.samplename==n.sampleobj.name))||t.get(e).push({samplename:n.sampleobj.name,items:[]})}for(const[e,n]of t)i.push({name:e,samples:n})}else if(t.cohort&&t.cohort.annotation&&e.groupsamplebyattr){const n=new Map,o=[];for(const[r,i]of s)Zs(r,i,n,o,t,e);if(r)for(const s of r)if(s.dt!=P.dtsnvindel)console.log("unknown dt when grouping samples from vcf data: "+s.dt);else for(const r of s.sampledata)Zs(r.sampleobj.name,[],n,o,t,e);for(const t of n.values())if(i.push(t),e.groupsamplebyattr.key2group){const n=e.groupsamplebyattr.key2group.get(t.name);n&&(t.sampletotalnum=n.samples.length)}o.length&&i.push({name:"Unannotated",samples:o});for(const e of i)for(const n of e.samples)t.cohort.annotation[n.samplename]&&(n.sampletype=t.cohort.annotation[n.samplename].sample_type)}else{const t=[];for(const[e,n]of s)t.push({samplename:e,items:n});if(r)for(const e of r)if(e.dt!=P.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){let e=!0;for(const r of 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c=l.join(o.groupsamplebyattr.attrnamespacer);if(!n.has(c)){const t=[];for(const e of o.groupsamplebyattr.attrlst){const n=i[e.k];if(null==n)break;const r={k:e.k,kvalue:n};e.full&&(r.full=e.full,r.fullvalue=i[e.full]),t.push(r)}const e=[];for(const t of o.groupsamplebyattr.attrlst){const n=i[t.k];if(null==n)break;const r=(t.full?i[t.full]:null)||n;e.push(r)}n.set(c,{name:c,samples:[],attributes:t})}let u=!0;for(const r of n.get(c).samples)if(r.samplename==t){for(const t of e)r.items.push(t);u=!1;break}u&&n.get(c).samples.push({samplename:t,items:e})}function Us(t){return Number.isFinite(t.dna_mintotalreads)?Number.isFinite(t.rna_mintotalreads)?Number.isFinite(t.hetsnp_minbaf)?Number.isFinite(t.hetsnp_maxbaf)?Number.isFinite(t.rnapileup_q)?Number.isFinite(t.rnapileup_Q)?void 0:"invalid value for rnapileup_Q":"invalid value for rnapileup_q":"invalid value for hetsnp_maxbaf":"invalid value for hetsnp_minbaf":"invalid value for rna_mintotalreads":"invalid value for 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o.dnacount.f=s+e==0?0:s/(s+e),e+s>=n.dna_mintotalreads&&o.dnacount.f>=n.hetsnp_minbaf&&o.dnacount.f<=n.hetsnp_maxbaf&&(o.dnacount.ishet=!0),o}return null}}async function Hs(t,e,n,r,o){const i=await Ws(y().join(s().tpmasterdir,e.file),n+":"+r+"-"+o),a=new Map;if(i)for(const t of i){const e=t.split("\t"),n=JSON.parse(e[3]),r=Number.parseInt(e[1]),s=Number.parseInt(e[2]);if(a.has(n.name)){const t=a.get(n.name);t.start=Math.min(t.start,r),t.stop=Math.max(t.stop,s)}else a.set(n.name,{gene:n.name,start:r,stop:s,exonunion:[]});const o=a.get(n.name);if(n.exon)for(const t of n.exon){const e=o.exonunion.find((e=>Math.max(e[0],t[0])<Math.min(e[1],t[1])));e?(e[0]=Math.min(t[0],e[0]),e[1]=Math.max(t[1],e[1])):o.exonunion.push([t[0],t[1]])}}for(const[t,e]of a)e.exonlength=e.exonunion.reduce(((t,e)=>t+e[1]-e[0]),0);return a}async function Ws(t,e,n){return new Promise(((r,s)=>{const 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if(n.namehover&&!t.query.noNameHover){const t=Math.max(10,n.start+10);M.fillStyle="white",M.fillRect(t,s,n.namewidth+10,o),M.strokeStyle=r,M.strokeRect(t+1.5,s+.5,n.namewidth+10-3,o-2),M.fillStyle=r,M.textAlign="center",M.fillText(n.namestr,t+n.namewidth/2+5,s+o/2)}else n.namein&&(M.textAlign="center",M.fillStyle="white",M.fillText(n.namestr,(Math.max(0,n.start)+Math.min(l,n.stop))/2,s+o/2))}const L={height:D,mapisoform:C,mapexon:R,returngmdata:_};if(0==N.length)return L.src=A.toDataURL(),L;const $=[];M.textAlign="center",M.textBaseline="middle";for(const[e,n]of N.entries()){const e=p&&n.category&&p[n.category]?p[n.category].color:n.color||u,r=n.canvas,s=(o+i)*(r.stack-1);n.genomicseq=(await F.Kf(q,n.chr+":"+(n.start+1)+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase();const l=(0,P.nt2aa)(n);for(const e of n.rglst){const i=t.query.rglst[e.idx];let c=0;for(let n=0;n<e.idx;n++)c+=t.query.rglst[n].width+a;const u=i.width/(i.stop-i.start),f=Math.min(o,3*u),d=f<8?null:f;let 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Please choose a smaller range.`}(e),e.query.__genomes=t;const r=e.get("X-Auth-Token");if(r&&(e.query.token=r),await jt(e.query.gdcFileUUID,Oe(t),e.query),e.query.stream2download)return void await async function(t,e){const{host:n,headers:r}=Oe(t.query.__genomes).getHostHeaders(t.query);r.compression=!1;const s=y().join(n.rest,"/slicing/view/",t.query.gdcFileUUID+"?region="+t.query.gdcFilePosition);e.statusCode=200;try{await Ot(v().stream(s,{method:"get",headers:r}),e)}catch(t){if("ERR_STREAM_PREMATURE_CLOSE"==t.code)return;t.stack&&console.log(t.stack),e.send({error:t.message||t})}}(e,n);e.query.file=nn(e)}if(e.query.downloadgdc)return void n.send(await rn(e));if(e.query.clientdownloadgdcslice)return void await async function(t,e){if(!t.query.gdcFileUUID||!t.query.gdcFilePosition||!t.query.file)throw"clientdownloadgdcslice: unauthorized access";const n=y().join(s().cachedir_bam,t.query.file),r=await m().promises.readFile(n);e.writeHead(200,{"Content-Type":"application/octet-stream","Content-Disposition":"attachment; filename=gdc.bam","Content-Length":r.length}),e.end(Buffer.from(r,"binary"))}(e,n);if(!e.query.genome)throw".genome missing";const r=t[e.query.genome];if(!r)throw"invalid genome";if(e.query.getread)return void n.send(await async function(t,e){if(!e.query.chr)throw".chr missing";if(!e.query.qname)throw".qname missing";if(e.query.qname=decodeURIComponent(e.query.qname),!Number.isInteger(e.query.start))throw".start is not integer";if(!Number.isInteger(e.query.stop))throw".stop is not integer";const n={chr:e.query.chr,start:e.query.start,stop:e.query.stop,scale:()=>{},ntwidth:10},r=await async function(t,e){const[n,r]=await Fe(t);let s,o,i,a,l;if(t.query.unknownorder){if(!Number.isInteger(t.query.readstart)||!Number.isInteger(t.query.readstop))throw"readstart/stop not provided for read with unknown order";i=t.query.readstart,a=t.query.readstop}if(await F.UE({isbam:!0,args:["view",n,(t.query.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+e.start+"-"+e.stop],dir:r,callback:(n,r)=>{if(n.split("\t")[0]!=t.query.qname)return;const c=Ue({sam_info:n,keepallboxes:!0,keepmatepos:!0,keepunmappedread:!0},e);if(c&&(!t.query.show_unmapped||!c.discord_unmapped2)&&(t.query.start==c.segstart_original&&t.query.stop==c.segstop||t.query.paired||t.query.show_unmapped))if(t.query.show_unmapped&&t.query.getfirst){if(c.islast)return r.kill(),void(l=[c])}else if(t.query.show_unmapped&&t.query.getlast){if(c.isfirst)return r.kill(),void(l=[c])}else if(t.query.getfirst){if(c.isfirst)return r.kill(),void(l=[c])}else if(t.query.getlast){if(c.islast)return r.kill(),void(l=[c])}else if(t.query.unknownorder){if(c.segstart==i&&c.segstop==a)return r.kill(),void(l=[c])}else if(c.isfirst?s=c:c.islast&&(o=c),s&&o)return r.kill(),void(l=[s,o])}}),l){if(t.query.altseqs){const e={query_seq:l[0].seq,refseqs:t.query.refseqs,altseqs:t.query.altseqs,cigar_seq:l[0].cigarstr,start_position:l[0].segstart,ref_positions:t.query.ref_positions,refalleles:t.query.refalleles,altalleles:t.query.altalleles},n=(await(0,Q.run_rust)("align",JSON.stringify(e))).split("\n");let r;for(let t of n)t.includes("Final_output:")?r=JSON.parse(t.replace("Final_output:","")):console.log(t);l.alignments=r}return l}l=[],s&&l.push(s);o&&l.push(o);return l.length?l:null}(e,n);if(!r){if(e.query.show_unmapped)throw"mate not found";throw"read not found"}const s=[];for(const n of r)n.discord_unmapped1?s.push(await tn(n,t,e.query)):s.push(await en(n,t,e.query));r.alignments&&(s[0].alignments=r.alignments);return{lst:s}}(r,e));const o=s().debugmode?new Date:null,i=await async function(t,e){const[n,r]=await Fe(e),s={genome:t,file:n,dir:r,asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1};if(e.query.pileupheight&&(s.pileupheight=Number(e.query.pileupheight),Number.isNaN(s.pileupheight)))throw".pileupheight is not integer";e.query.drop_pcrduplicates&&(s.drop_pcrduplicates=!0);e.query.drop_supplementary_alignments&&(s.drop_supplementary_alignments=!0);if(e.query.variant){s.diff_score_plotwidth=Number(e.query.diff_score_plotwidth),e.query.max_diff_score&&(s.max_diff_score=Number(e.query.max_diff_score),s.min_diff_score=Number(e.query.min_diff_score));const t=e.query.variant.split(".");if(s.strictness=e.query.strictness,!Number.isInteger(t.length%4))throw"invalid variant, not chr.pos.ref.alt";s.alleleAlreadyUpdated=e.query.alleleAlreadyUpdated,s.alleleAlreadyUpdated&&(s.altseqs=e.query.altseqs,s.refseqs=e.query.refseqs,s.altalleles=e.query.altalleles,s.refalleles=e.query.refalleles,s.leftflankseqs=e.query.leftflankseqs,s.rightflankseqs=e.query.rightflankseqs,s.ref_positions=e.query.ref_positions);const n=t.length/4,r=[];for(let e=0;e<n;e++)r.push({chr:t[4*e],pos:Number(t[4*e+1]),ref:t[4*e+2],alt:t[4*e+3]});if(s.variant=r,e.query.alignOneGroup&&(s.alignOneGroup=e.query.alignOneGroup),Number.isNaN(s.variant.pos))throw"variant pos not integer"}else if(e.query.sv){const t=e.query.sv.split(".");if(t.length<6)throw"invalid sv, not chrA.posA.chrB.posB";if(s.sv={chrA:t[0],startA:Number(t[1]),strandA:Number(t[2]),chrB:t[3],startB:Number(t[4]),strandB:Number(t[5])},Number.isNaN(s.sv.startA))throw"sv.startA not integer";if(Number.isNaN(s.sv.startB))throw"sv.startB not integer"}if(Number.isFinite(Number(e.query.stackstart))){if(!e.query.stackstop)throw".stackstop missing";if(s.partstack={start:Number(e.query.stackstart),stop:Number(e.query.stackstop)},Number.isNaN(s.partstack.start))throw".stackstart not integer";if(Number.isNaN(s.partstack.stop))throw".stackstop not integer";if(!e.query.grouptype)throw".grouptype required for partstack";s.grouptype=e.query.grouptype}e.query.gdc||(e.query.nochr?s.nochr="string"==typeof e.query.nochr?JSON.parse(e.query.nochr):e.query.nochr:s.nochr=await F.Dp(s.file,t,s.dir));if(s.regions=e.query.regions,!Array.isArray(s.regions)||0==s.regions.length)throw"q.regions[] not non-empty array";let o=0;for(const t of s.regions){if(!t.chr)throw".chr missing from a region";if(!Number.isInteger(t.start))throw".start not integer of a region";if(!Number.isInteger(t.stop))throw".stop not integer of a region";t.scale=e=>Math.ceil(t.width*(e-t.start)/(t.stop-t.start)),t.ntwidth=t.width/(t.stop-t.start),o=Math.max(o,t.ntwidth)}return s.stacksegspacing=Math.max(ke,qe*o),s.readcount_skipped=0,s}(r,e);n.send(await async function(t){await async function(t){if(t.variant){let e=0,n=0,r=0,s=t.variant[0].pos,o=t.variant[0].pos+Math.max(t.variant[0].ref.length,t.variant[0].alt.length);for(const i of t.variant){const t=Math.abs(i.pos-Math.max(i.ref.length,i.alt.length));t>e&&(e=t,n=r),s>i.pos&&(s=i.pos),o<i.pos+Math.max(i.ref.length,i.alt.length)&&(o=i.pos+Math.max(i.ref.length,i.alt.length)),r+=1}e=Math.floor(1.5*Math.max(t.variant[n].ref.length,t.variant[n].alt.length));const i={chr:t.variant[0].chr,start:s-e,stop:o+e};return await De(t,[i]),await Le(i,t),void(t.regions[0].lines=i.lines)}await De(t,t.regions);for(const e of t.regions)await Le(e,t)}(t),t.totalnumreads=t.regions.reduce(((t,e)=>t+e.lines.length),0);const e={nochr:t.nochr,count:{r:t.totalnumreads},groups:[]};t.read_limit_reached&&(e.count.read_limit_reached=t.read_limit_reached);t.canvaswidth=t.regions[t.regions.length-1].x+t.regions[t.regions.length-1].width;{const n=await async function(t){const e=[],n=[];let r=0;for(const s of t.regions){for(const t of s.lines)e.push({sam_info:t,tempscore:""});r=s.x+s.width,n.push(r)}if(0==e.length)return{groups:[{type:lt,regions:mt(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]};if(t.variant){if(1==t.regions.length)return await async function(t,e,n){const r=t.regions[0].lines[0].split("\t")[9].length;let s=!1,o=[],i=[],a=[],l=[],c=[],u=[],f=[];if(t.alleleAlreadyUpdated)o=t.leftflankseqs,i=t.rightflankseqs,u=t.refseqs,f=t.altseqs,a=t.refalleles,l=t.altalleles,c=t.ref_positions,0!=u[0].toUpperCase().localeCompare((o[0]+a[0]+i[0]).toUpperCase())&&(console.log("Reference allele is not correct for variant 0"),s=!0);else{let e,n,s=0;for(const o of t.variant){let i="",u="";if(!(0!=o.ref.length&&"-"!=o.ref||"-"!=o.alt&&0!=o.alt.length))throw"Both Ref and Alt alleles are missing";if(0==o.ref.length||"-"==o.ref)i=(await F.Kf(t.genome,o.chr+":"+o.pos+"-"+o.pos)).split("\n").slice(1).join("").toUpperCase(),u=i+o.alt,o.pos-=1;else if("-"==o.alt||0==o.alt.length){const e=(await F.Kf(t.genome,o.chr+":"+o.pos+"-"+o.pos)).split("\n").slice(1).join("").toUpperCase();i=e+o.ref,u=e,o.pos-=1}else u=o.alt,i=o.ref;const f=o.pos,d=i.toUpperCase(),h=u.toUpperCase();0==s?(e=f-r,n=f+i.length+1+r):(f-r<e&&(e=f-r),f+i.length+1+r>n&&(n=f+i.length+1+r)),a.push(d),l.push(h),c.push(f),s+=1}s=0;for(const r of t.variant){const d=(await F.Kf(t.genome,r.chr+":"+e+"-"+c[s])).split("\n").slice(1).join("").toUpperCase(),h=(await F.Kf(t.genome,r.chr+":"+(c[s]+a[s].length+1)+"-"+n)).split("\n").slice(1).join("").toUpperCase(),p=d+a[s]+h,m=d+l[s]+h;console.log(r.chr+"."+c[s]+"."+a[s]+"."+l[s]),s+=1,o.push(d),i.push(h),u.push(p),f.push(m)}}const d=[];for(let t=0;t<e.length;t++){const n=e[t].sam_info.split("\t");d.push({read_sequence:n[9],start_position:Number(n[3]),cigar:n[5],flag:Number(n[1])})}const h=[];for(let t=0;t<a.length;t++)h.push({ref_position:Number(c[t]),refallele:a[t],altallele:l[t],refseq:u[t],altseq:f[t],leftflankseq:o[t],rightflankseq:i[t]});Number.isFinite(Number(t.strictness))||(t.strictness=1);const p={reads:d,alleles:h,strictness:Number(t.strictness)},m=new Date,g=await(0,Q.run_rust)("indel",JSON.stringify(p)),y=new Date;console.log("Time taken to run rust indel pipeline:",y-m,"ms");const b=g.split("\n");let v,w,_,x,k,q,N=0;for(let t of b)t.includes("Final_output:")?v=JSON.parse(JSON.parse(t.replace("Final_output:",""))):1==a.length&&t.includes("fisher_strand:")?(w=JSON.parse(t.replace("fisher_strand:","")),_=w.alternate_forward_count,x=w.alternate_reverse_count,k=w.reference_forward_count,q=w.reference_reverse_count,N=w.p_value):console.log(t);if(0==v.length)throw"No reads available for variant typing";let S=!1;1==t.variant.length&&N>60&&(S=!0);const A=pt(t);t.variant.length;let M=1;for(let n=0;n<v.length;n++){const r=v[n],s=r.read_number,o=r.categories,i=r.categories[0],a=[];if(o.length>1){for(let t=1;t<o.length;t++)a.push(o[t]);o.length-1>M&&(M=o.length-1)}if(i.includes("alt"))for(let n=0;n<t.variant.length;n++)i=="alt"+n.toString()&&A[ut+n.toString()]&&(e[s].tempscore=["alt"+n.toString()],A[ut+n.toString()].templates.push(e[s]));else"ref"==i?A[ct]&&(e[s].tempscore=["ref"],A[ct].templates.push(e[s])):"none"==i?A[ft]&&(e[s].tempscore=a,A[ft].templates.push(e[s])):"amb"==i?A[dt]&&(e[s].tempscore=a,A[dt].templates.push(e[s])):console.log("Unaccounted group, please check")}const T=[];for(const e in A){const r=A[e];if(0!=r.templates.length){if(e.includes(ut))for(let n=0;n<t.variant.length;n++)e==ut+n.toString()&&(1==t.variant.length?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the alternative allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the alternative allele"}):1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read support the alternative allele with "+l[n]+" sequence"}):r.messages.push({isheader:!0,t:r.templates.length+" reads support the alternative allele with "+l[n]+" sequence"}));else e==dt?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" ambiguous read"}):r.messages.push({isheader:!0,t:r.templates.length+" ambiguous reads"}):e==ct?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the reference allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the reference allele"}):e==ft?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting neither reference nor alternative alleles"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting neither reference nor alternative alleles"}):console.log("Unaccounted group, please check");r.widths=n,T.push(r)}}const C=[];for(let t=0;t<T.length;t++)T[t].type.includes("support_alt")&&C.push(T[t]);for(let t=0;t<T.length;t++)"support_ref"==T[t].type&&C.push(T[t]);for(let t=0;t<T.length;t++)"support_no"==T[t].type&&C.push(T[t]);for(let t=0;t<T.length;t++)"support_amb"==T[t].type&&C.push(T[t]);return{groups:C,refalleleerror:s,ref_positions:c,refalleles:a,altalleles:l,max_diff_score:M,min_diff_score:0,strand_probability:N,strand_significance:S,refseqs:u,altseqs:f,leftflankseqs:o,rightflankseqs:i,alternate_forward_count:_,alternate_reverse_count:x,reference_forward_count:k,reference_reverse_count:q}}(t,e,n);console.log("Indel pipeline works only in single region. Please check!")}if(t.sv&&t.regions.length>1)return async function(t,e,n){const r=pt(e),s=[];for(let t=0;t<e.regions.length;t++){const n=e.regions[t],r=(await F.Kf(e.genome,n.chr+":"+n.start+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase(),o=[];for(const e of n.lines)o.push({sam_info:e,tempscore:"",ridx:t});const i={refseq:r,start:n.start,stop:n.stop,entries:o};0==t?(i.chr=e.sv.chrA,i.pos=e.sv.startA):1==t?(i.chr=e.sv.chrB,i.pos=e.sv.startB):console.log("More than two regions, please check"),s.push(i)}const o=new Date,i=(await(0,Q.run_rust)("sv",JSON.stringify(s))).split("\n"),a=new Date;let l,c;console.log("Time taken to run rust SV pipeline:",a-o,"ms");for(let t of i)t.includes("multi_region_templates:")?l=JSON.parse(t.replace("multi_region_templates:","")):t.includes("single_region_templates:")&&(c=JSON.parse(t.replace("single_region_templates:","")));if(!e.grouptype||"support_sv"==e.grouptype)for(const t of l)r[ht].templates.push(t);if(!e.grouptype||"support_ref"==e.grouptype)for(const t of c)r[ct].templates.push(t);const u=[];for(const t in r){const e=r[t];0!=e.templates.length&&(t==ht?1==e.templates.length?e.messages.push({isheader:!0,t:e.templates.length+" read supporting SV/fusion"}):e.messages.push({isheader:!0,t:e.templates.length+" reads supporting SV/fusion"}):t==ct&&e.messages.push({isheader:!0,t:e.templates.length+" reads supporting reference allele"}),e.widths=n,u.push(e))}return{groups:u}}(0,t,n);return{groups:[{type:lt,regions:mt(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]}}(t);t.groups=n.groups,t.variant&&(e.ref_alleles=n.refalleles,e.alt_alleles=n.altalleles,e.allele_positions=n.ref_positions,e.strand_probability=n.strand_probability,e.alternate_forward_count=n.alternate_forward_count,e.reference_forward_count=n.reference_forward_count,e.alternate_reverse_count=n.alternate_reverse_count,e.reference_reverse_count=n.reference_reverse_count,1==n.strand_significance&&(e.strand_significance=!0),t.alleleAlreadyUpdated||(e.refseqs=n.refseqs,e.altseqs=n.altseqs,e.leftflankseqs=n.leftflankseqs,e.rightflankseqs=n.rightflankseqs,e.ref_positions=n.ref_positions,e.refalleles=n.refalleles,e.altalleles=n.altalleles)),Number.isFinite(t.max_diff_score)&&t.variant?(e.max_diff_score=t.max_diff_score,e.min_diff_score=t.min_diff_score):Number.isFinite(n.max_diff_score)&&(e.max_diff_score=n.max_diff_score,e.min_diff_score=n.min_diff_score),n.refalleleerror&&(e.refalleleerror=n.refalleleerror)}if(0==e.count.r)throw"No reads in view range.";if(t.alignOneGroup){const e=t.groups.find((e=>e.type==t.alignOneGroup));if(!e)throw"cannot find group for realignment";let n=Ze(t,e);return n=Ge(e,t,n),await async function(t,e,n){let r;if(e.variant)if("support_ref"==t.type){let s=e.leftflankseqs[0].length;r=t.partstack?await Pe(n,s,t.partstack.start,t.partstack.stop,e.refseqs[0]):await Pe(n,s,0,0,e.refseqs[0])}else if("support_no"==t.type){let s=e.leftflankseqs[0].length;r=t.partstack?await Pe(n,s,t.partstack.start,t.partstack.stop):await Pe(n,s)}else{if("support_amb"==t.type)throw"Realignment of reads in ambiguous group is not currently implemented.";if(t.type.includes("support_alt")){for(let s=0;s<e.variant.length;s++)if(t.type=="support_alt"+s.toString()){let o=e.leftflankseqs[s].length;r=t.partstack?await Pe(n,o,t.partstack.start,t.partstack.stop,e.altseqs[s]):await Pe(n,o,0,0,e.altseqs[s])}}else console.log("Unaccounted group, please check")}return{alignmentData:r}}(e,t,n)}let n=[];for(const r of t.groups){let s=Ze(t,r);s=Ge(r,t,s),await Be(r,t,s),await ze(s,t),He(r,s,t);const o={type:r.type,width:t.canvaswidth,height:r.canvasheight,stackheight:r.stackheight,stackcount:r.stacks.length,allowpartstack:r.allowpartstack,templatebox:r.returntemplatebox,count:{r:s.reduce(((t,e)=>t+e.segments.length),0)}},i=(0,S.createCanvas)(t.canvaswidth*t.devicePixelRatio,r.canvasheight*t.devicePixelRatio),a=i.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio),a.textAlign="center",a.textBaseline="middle",o.messages=r.messages,o.messagerowheights=0;for(const e of s)Ke(a,e,r,t);Qe(a,r,t,s),t.asPaired&&(o.count.t=s.length),t.variant&&(o.diff_scores_img=await Ie(t,r,s,e.max_diff_score,e.min_diff_score),"support_alt0"==o.type?o.group_color=ie:"support_alt1"==o.type?o.group_color=ae:"support_alt2"==o.type?o.group_color=le:"support_alt3"==o.type?o.group_color=ce:"support_alt4"==o.type?o.group_color=ue:"support_alt5"==o.type?o.group_color=fe:"support_ref"==o.type&&(o.group_color=de)),o.src=i.toDataURL(),e.groups.push(o),n=[...n,...s]}t.readcount_skipped&&(e.count.skipped=t.readcount_skipped);t.getcolorscale&&(e.colorscale=function(t){const e=160,n=20,r=1,s=12,o=5,i=100,a=4,l=i+e+10,c=2*s+o+a+4*(n+r),u=(0,S.createCanvas)(t.devicePixelRatio*l,t.devicePixelRatio*c),f=u.getContext("2d");t.devicePixelRatio>1&&f.scale(t.devicePixelRatio,t.devicePixelRatio);f.fillStyle="black",f.font=s+"pt Arial",f.textAlign="center",f.fillText("Base quality",i+e/2,s);let d=2*s+o;function h(t,r,s){const o=i,a=f.createLinearGradient(o,s,o+e,s);a.addColorStop(0,r),a.addColorStop(1,t),f.fillStyle=a,f.fillRect(o,s,e,n)}return f.strokeStyle="black",f.beginPath(),f.moveTo(i,d),f.lineTo(i,d+a),f.moveTo(i+e/4,d),f.lineTo(i+e/4,d+a),f.moveTo(i+e/2,d),f.lineTo(i+e/2,d+a),f.moveTo(i+3*e/4,d),f.lineTo(i+3*e/4,d+a),f.moveTo(i+e,d),f.lineTo(i+e,d+a),f.closePath(),f.stroke(),f.fillText(40,i,d),f.fillText(30,i+e/4,d),f.fillText(20,i+e/2,d),f.fillText(10,i+3*e/4,d),f.fillText(0,i+e,d),f.textAlign="left",f.textBaseline="middle",d+=a,f.fillText("Match",0,d+n/2),h(Rt,It,d),d+=n+r,f.fillStyle="black",f.fillText("Mismatch",0,d+n/2),h(Zt,zt,d),d+=n+r,f.fillStyle="black",f.fillText("Softclip",0,d+n/2),h(Gt,Bt,d),d+=n+r,f.fillStyle="black",f.fillText("Insertion",0,d+n/2),h(Xt,Kt,d),{width:l,height:c,src:u.toDataURL()}}(t));if(!t.partstack)if(0==e.count.r);else{if(!t.pileupheight)throw"pileupheight missing";e.pileup_data=await async function(t,e){const 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function(t,e,n){if(!t.junctionAposlst)throw".junctionAposlst[] missing";let r,s=t.junctionB.start,o=t.junctionB.stop;t.junctionAposlst.forEach((t=>{s=Math.min(s,t[0]),o=Math.max(o,t[1])}));let i=[];if(await F.UE({args:[n.file||n.url,t.junctionB.chr+":"+s+"-"+o],dir:n.dir,callback:e=>{const n=e.split("\t"),s=Number.parseInt(n[1]),o=Number.parseInt(n[2]);if(s==t.junctionB.start&&o==t.junctionB.stop)r=JSON.parse(n[5]);else for(const[e,r]of t.junctionAposlst)if(e==s&&r==o){const t=JSON.parse(n[5]);t.start=s,t.stop=o,i.push(t);break}}}),!r)throw"jB not found";if(0==i.length)throw"none of jA is found";const a=gn(r,t,e,n);if(0==a.length)throw"no sample passing filters for junctionB";const l=new Set;a.forEach((t=>l.add(t.i)));const c=[];for(const e of i){const n=[];for(const r of e.samples)l.has(r.i)&&(t.readcountCutoff&&r.readcount<t.readcountCutoff||n.push(r));c.push({start:e.start,stop:e.stop,v:Math.floor(yn(n,.5))})}return{lst:c}}(t,e,n);const r={};if(t.iscustom&&t.getsamples){const t=await F.ZD(mn(n),n.dir);if(t[0]){const e=t[0].split("\t");e.length>5&&(r.sample2client=e.slice(5))}}if(!t.rglst)throw"rglst missing";if(n.viewrangeupperlimit){if(t.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>=n.viewrangeupperlimit)throw"zoom in under "+common.bplen(n.viewrangeupperlimit)+" to view details"}let s=0,o=0;const i=[],a=new Set,l=new Set;for(const r of t.rglst)await F.UE({args:[mn(n),r.chr+":"+r.start+"-"+r.stop],dir:n.dir,callback:c=>{const u=c.split("\t"),f=Number.parseInt(u[1]),d=Number.parseInt(u[2]);if(n.file2){u[3];const e=u[4];let n;if("known"==e)n="canonical";else{if("novel"!=e)throw"unknown rnapeg type: "+e;n=pn}if(t.infoFilter&&t.infoFilter.type&&t.infoFilter.type[n])return;const a={chr:r.chr,start:f,stop:d,info:{type:{lst:[{attrValue:n}]}}},l=[];for(let t=5;t<u.length;t++){const e=u[t];if(!e)continue;const n=Number.parseInt(e);Number.isNaN(n)||(n<=0||(l.push({readcount:n}),s=Math.max(s,n)))}if(0==l.length)return;if(o++,a.sampleCount=l.length,1==a.sampleCount)a.medianReadCount=l[0].readcount;else{const t=yn(l,.05,.25,.5,.75,.95);a.medianReadCount=t[2],a.readcountBoxplot={percentile:t}}i.push(a)}else{u[3],u[4];if(!(f>=r.start&&f<=r.stop||d>=r.start&&d<=r.stop))return;o++;const c={chr:r.chr,start:f,stop:d,info:{type:{lst:[]}}},h=JSON.parse(u[5]);if(h.sv){c.sv=h.sv;const t=c.chr+"."+c.start+"."+c.sv.mate.chr+"."+c.sv.mate.start;if(a.has(t))return;a.add(t),a.add(c.sv.mate.chr+"."+c.sv.mate.start+"."+c.chr+"."+c.start)}if(h.canonical&&c.info.type.lst.push({attrValue:"canonical"}),h.events)for(const t in h.events){const e=h.events[t];e.__ek=t,c.info.type.lst.push(e)}else h.canonical||c.info.type.lst.push({attrValue:pn});if(t.infoFilter&&t.infoFilter.type)for(const e of c.info.type.lst)if(t.infoFilter.type[e.attrValue])return;const p=gn(h,t,e,n);if(0==p.length)return;if((h.exonleft||h.exonright||h.exonleftin||h.exonrightin||h.intronleft||h.intronright||h.leftout||h.rightout)&&(c.ongene={},h.exonleft&&(c.ongene.exonleft=h.exonleft),h.exonright&&(c.ongene.exonright=h.exonright),h.exonleftin&&(c.ongene.exonleftin=h.exonleftin),h.exonrightin&&(c.ongene.exonrightin=h.exonrightin),h.intronleft&&(c.ongene.intronleft=h.intronleft),h.intronright&&(c.ongene.intronright=h.intronright),h.leftout&&(c.ongene.leftout=h.leftout),h.rightout&&(c.ongene.rightout=h.rightout)),p.forEach((t=>{l.add(t.i),s=Math.max(s,t.readcount)})),c.sampleCount=p.length,1==c.sampleCount)c.medianReadCount=p[0].readcount;else{const t=yn(p,.05,.25,.5,.75,.95);c.medianReadCount=t[2],c.readcountBoxplot={percentile:t}}i.push(c)}}});r.lst=i,r.maxreadcount=s,r.junctiontotalnumber=o,l.size;return r}(r,o,i);n.send(a)}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}(bs)),ks.post(qs+"/mdscnv",(function(t,e){const[n,r,o,i]=Rs(t.query);if(n)return e.send({error:n});if(!t.query.rglst)return e.send({error:"rglst missing"});if(!t.query.gain)return e.send({error:".gain missing"});if(!t.query.loss)return e.send({error:".loss missing"});if(i.viewrangeupperlimit){if(t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>=i.viewrangeupperlimit)return e.send({error:"zoom in under "+P.bplen(i.viewrangeupperlimit)+" to view details"})}if(t.query.permanentHierarchy){const n=function(t,e){if(!e.cohort)return".cohort missing from ds";if(!e.cohort.hierarchies)return".hierarchies missing from ds.cohort";if(!e.cohort.hierarchies.lst)return".hierarchies.lst[] missing from ds.cohort";const n=e.cohort.hierarchies.lst.find((e=>e.name==t.permanentHierarchy.hierarchyname));if(!n)return"unknown hierarchy "+t.permanentHierarchy.hierarchyname;if(!n.levels)return".levels[] missing in 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a=JSON.parse(r[3]);if(t.query.valueCutoff&&Math.abs(a.value)<t.query.valueCutoff)return;if(a.sample&&o.cohort&&o.cohort.annotation){const e=o.cohort.annotation[a.sample];if(!e)return;if(t.query.cohortOnlyAttr&&o.cohort&&o.cohort.annotation){let n=!1;for(const r in t.query.cohortOnlyAttr){const s=e[r];if(s&&t.query.cohortOnlyAttr[r][s]){n=!0;break}}if(!n)return}if(t.query.cohortHiddenAttr&&o.cohort.attributes){let n=!1;for(const r in t.query.cohortHiddenAttr){o.cohort.attributes.lst.find((t=>t.key==r)).isNumeric;const s=e[r];if(s){if(t.query.cohortHiddenAttr[r][s]){n=!0;break}}else if(t.query.cohortHiddenAttr[r][xs]){n=!0;break}}if(n)return}}a.value>0?(l.count++,l.samples.add(a.sample)):a.value<0&&(c.count++,c.samples.add(a.sample));const u=Math.max(e.start,s),h=Math.min(e.stop,i);let p,m;e.reverse?(p=Math.floor((e.stop-h)/f),m=Math.floor((e.stop-u)/f)):(p=Math.floor((u-e.start)/f),m=Math.floor((h-e.start)/f));for(let t=p;t<m;t++)a.value>0?d[t].positive++:a.value<0&&d[t].negative++}));const h=[];a.stderr.on("data",(t=>h.push(t))),a.on("close",(t=>{const e=h.join("");!e||gs(e)?n(d):r(e)}))}));a.push(n)}Promise.all(a).then((n=>{const r=t.query.rglst.reduce(((e,n)=>e+n.width+t.query.regionspace),0)-t.query.regionspace,s=(0,S.createCanvas)(r,t.query.gain.barheight+t.query.loss.barheight),a=s.getContext("2d"),u={gain:{count:l.count,samplenumber:l.samples.size},loss:{count:c.count,samplenumber:c.samples.size},maxvalue:0};if(l.count+c.count==0)return a.font="15px Arial",a.fillStyle="#aaa",a.textAlign="center",a.textBaseline="middle",a.fillText("No data in view range",r/2,t.query.gain.barheight),u.src=s.toDataURL(),void e.send(u);for(const t of n)for(const e of t)u.maxvalue=Math.max(u.maxvalue,e.positive,e.negative);const f=t.query.maxvalue||u.maxvalue;let d=0;for(const e of n){for(const n of e){if(n.positive){a.fillStyle=t.query.gain.color||"#67a9cf";const e=Math.ceil(t.query.gain.barheight*Math.min(f,n.positive)/f),r=t.query.gain.barheight-e;a.fillRect(d,r,1,e)}if(n.negative){a.fillStyle=t.query.loss.color||"#ef8a62";const e=Math.ceil(t.query.loss.barheight*Math.min(f,n.negative)/f),r=t.query.gain.barheight;a.fillRect(d,r,1,e)}d++}d+=t.query.regionspace}if(u.src=s.toDataURL(),l.samples.size||c.samples.size){const t=new Set([...l.samples,...c.samples]),[e,n]=function(t,e,n){if(!t.cohort||!t.cohort.annotation||0==n.length)return[null,null];const r=[];for(const e of n){const n=t.cohort.annotation[e];n&&r.push(n)}if(0==r.length)return[null,null];let s,o;if(t.cohort.attributes){s=[];for(const n of t.cohort.attributes.lst){const o={label:n.label,key:n.key};if(n.isNumeric){o.isNumeric=!0;continue}const i=new Map;let a=0;for(const e of r){const r=e[n.key];null!=r?(i.has(r)||i.set(r,new Set),i.get(r).add(e[t.cohort.samplenamekey])):a++}const l=[...i];a&&l.push([xs,a]),l.sort(((t,e)=>e[1]-t[1])),o.values=[];for(const[t,r]of l){const s={name:t,sampleset:r};if(n.values&&n.values[t])for(const e in n.values[t])s[e]=n.values[t][e];e.attributeSummary&&e.attributeSummary[n.key]&&e.attributeSummary[n.key][t]&&(s.totalCount=e.attributeSummary[n.key][t]),o.values.push(s)}s.push(o)}}if(t.cohort.hierarchies){o={};for(const n of t.cohort.hierarchies.lst){const s=(0,V.Z)()((0,A.N)(r,n.levels));s.sum((t=>t.value));const i=[];s.eachBefore((r=>{const s={id:r.data.id,name:r.data.name,label:r.data.full,depth:r.depth};if(r.data.lst){s.sampleset=new Set;for(const e of r.data.lst)s.sampleset.add(e[t.cohort.samplenamekey])}r.children||(s.isleaf=1),e.hierarchySummary&&e.hierarchySummary[n.name]&&(s.totalCount=e.hierarchySummary[n.name][r.id]),i.push(s)})),o[n.name]=i}}return[s,o]}(o,i,[...t]);if(e){for(const t of e)for(const e of t.values){e.gain=0,e.loss=0;for(const t of e.sampleset)l.samples.has(t)&&e.gain++,c.samples.has(t)&&e.loss++;delete e.sampleset}u.attributeSummary=e}if(n){for(const t in n)for(const e of n[t])if(e.sampleset){e.gain=0,e.loss=0;for(const t of e.sampleset)l.samples.has(t)&&e.gain++,c.samples.has(t)&&e.loss++}u.hierarchySummary=n}}e.send(u)})).catch((t=>{e.send({error:t}),t.stack&&console.error(t.stack)}))})),ks.post(qs+"/mdssvcnv",(async function(t,e){let n,r,o,i,a,l,c,u,f;if(t.query.iscustom){if(n=bs[t.query.genome],!n)return e.send({error:"invalid genome"});if(r={},o={iscustom:1,file:t.query.file,url:t.query.url,indexURL:t.query.indexURL,allow_getallsamples:!0},t.query.checkexpressionrank){if(!t.query.checkexpressionrank.file&&!t.query.checkexpressionrank.url)return e.send({error:"no file or url for checkexpressionrank"});o.checkexpressionrank={file:t.query.checkexpressionrank.file,url:t.query.checkexpressionrank.url,indexURL:t.query.checkexpressionrank.indexURL}}if(t.query.checkvcf){let n;try{n=JSON.parse(t.query.checkvcf)}catch(t){return e.send({error:"invalid JSON for VCF object"})}if(!n.file&&!n.url)return e.send({error:"no file or url for custom VCF track"});n.type=P.mdsvcftype.vcf,o.checkvcf={info:n.info,tracks:[n]}}if(t.query.checkrnabam){if(!t.query.checkrnabam.samples)return e.send({error:"samples{} missing from checkrnabam"});let n=0;for(const e in t.query.checkrnabam.samples)n++;if(n>13)return e.send({error:"no more than 13 BAM files allowed"});const r=Us(t.query.checkrnabam);if(r)return e.send({error:r});o.checkrnabam=t.query.checkrnabam}}else{if(n=bs[t.query.genome],!n)return e.send({error:"invalid genome"});if(!n.datasets)return e.send({error:"genome is not equipped with datasets"});if(r=n.datasets[t.query.dslabel],!r)return e.send({error:"invalid dslabel"});if(t.query.getsample4disco)return function(t,e,n,r){if(t.query.iscustom)return e.send({error:"not for custom track"});if(!r.singlesamplemutationjson)return e.send({error:"singlesamplemutationjson not available for this dataset"});const o=t.query.getsample4disco,i=r.singlesamplemutationjson.samples[o];if(!i)return e.send({error:"no data"});const a=y().join(s().tpmasterdir,i);m().readFile(a,{encoding:"utf8"},((t,n)=>{if(t)return e.send({error:"error getting data for this sample"});e.send({text:n})}))}(t,e,0,r);if(t.query.gettrack4singlesample)return function(t,e,n){const r=t.query.gettrack4singlesample;if(t.query.iscustom)return e.send({error:"no server-side config available for custom track"});if(!n.sampleAssayTrack)return e.send({});return e.send({tracks:n.sampleAssayTrack.samples.get(r)})}(t,e,r);if(t.query.findsamplename)return function(t,e,n){if(t.query.iscustom)return e.send({error:"cannot search sample by name in custom track"});const r=t.query.findsamplename.toLowerCase(),s=[];if(!n.cohort.__samplelst){n.cohort.__samplelst=[];for(const t in n.cohort.annotation)n.cohort.__samplelst.push({name:t,low:t.toLowerCase()})}o(n.cohort.__samplelst);for(const t in n.queries){const e=n.queries[t];if(e.type==P.tkt.mdssvcnv&&e.groupsamplebyattr)for(const t of s){const r=n.cohort.annotation[t.name];if(!r)continue;const s=[];for(const t of e.groupsamplebyattr.attrlst){const e=r[t.k];e&&s.push({k:t.k,kvalue:e})}s.length&&(t.attributes=s,t.grouplabel=s.map((t=>t.kvalue)).join(e.groupsamplebyattr.attrnamespacer))}}if(n.cohort&&n.cohort.sampleAttribute&&n.cohort.sampleAttribute.attributes&&n.cohort.annotation)for(const t of s){const e=n.cohort.annotation[t.name];if(!e)continue;const r=[];for(const t in n.cohort.sampleAttribute.attributes){if(n.cohort.sampleAttribute.attributes[t].clientnoshow)continue;const s=e[t];null!=s&&r.push({k:t,v:s})}r.length&&(t.attr=r)}if(n.sampleAssayTrack)for(const t of s){const e=n.sampleAssayTrack.samples.get(t.name);e&&(t.num_assay_tracks=e.length)}if(n.cohort&&n.cohort.mutation_signature)for(const t in n.cohort.mutation_signature.sets){const e=n.cohort.mutation_signature.sets[t];if(e.samples)for(const t of s)e.samples.map.has(t.name)&&(t.mutation_signature=1)}if(n.singlesamplemutationjson)for(const t of s)n.singlesamplemutationjson.samples[t.name]&&(t.disco=1);return e.send({result:s});function o(t){for(const e of t){if(s.length>10)return;-1!=e.low.indexOf(r)&&(s.find((t=>t.name==e.name))||s.push(e))}}}(t,e,r);if(t.query.assaymap)return async function(t,e,n){try{if(!n.assayAvailability)throw"assay availability not enabled for this dataset";const r=new Set(t.query.skip_termids||[]),s=new Map;for(const e in n.cohort.annotation){if(t.query.key){if(n.cohort.annotation[e][t.query.key]!=t.query.value)continue}s.set(e,new Map)}for(const[t,e]of s){const s=n.assayAvailability.samples.get(t);if(s)for(const t of n.assayAvailability.assays)r.has(t.id)||s[t.id]&&e.set(t.id,"yes")}for(const t of s.keys())0==s.get(t).size&&s.delete(t);const o={};o.totalsample=s.size,o.terms=ts({sample2term:s,terms:n.assayAvailability.assays,config:{termidorder:t.query.termidorder}}),e.send(o)}catch(t){e.send({error:t.message||t})}}(t,e,r);if(!r.queries)return e.send({error:"dataset is not equipped with queries"});if(o=r.queries[t.query.querykey],!o)return e.send({error:"invalid querykey"})}if(t.query.getexpression4gene)return async function(t,e,n,r,o){try{const n=t.query.getexpression4gene;if(!n.chr)throw"chr missing";if(!Number.isFinite(n.start))throw"invalid start pos";if(!Number.isFinite(n.stop))throw"invalid stop pos";if(!n.name)throw"unknown gene name";if(o.checkrnabam){const r=bs[t.query.genome],s=r.tracks.find((t=>t.__isgene)),i=(await Hs(r,s,n.chr,n.start,n.stop)).get(n.name);if(!i)throw"no gene matching with "+n.name;const a={};await Fs(new Map([[n.name,i]]),n.chr,n.start,n.stop,o,a);const l={};for(const t of a.checkrnabam)if(t.genes){const e=t.genes.find((t=>t.gene==n.name));e&&(l[t.sample]=e)}return void e.send({sample2rnabam:l})}let i;if(o.iscustom?i=o.checkexpressionrank:o.expressionrank_querykey&&(i=r.queries[o.expressionrank_querykey]),!i)throw"missing expression data source";const a=i.file?null:await F.d1(i.url,i.indexURL),l=[];await F.UE({args:[i.file?y().join(s().tpmasterdir,i.file):i.url,n.chr+":"+n.start+"-"+n.stop],dir:a,callback:t=>{const e=t.split("\t");let r;try{r=JSON.parse(e[3])}catch(t){reject("invalid json from expression data")}r.sample&&r.gene&&Number.isFinite(r.value)&&(delete r.outlier,r.gene.toLowerCase()==n.name.toLowerCase()&&l.push(r))}});const c=function(t,e,n){const r={};if(t&&t.cohort&&t.cohort.annotation&&e.groupsamplebyattr&&e.groupsamplebyattr.attrlst){const s=new Map;for(const r of n){const n=t.cohort.annotation[r.sample];if(!n)continue;const o=[];for(const t of e.groupsamplebyattr.attrlst)o.push(n[t.k]);const i=o.join(",");s.has(i)||s.set(i,[]),s.get(i).push(r)}for(const t of s.values()){t.sort(((t,e)=>t.value-e.value));for(const e of t)e.rank=Ys(e.value,t),r[e.sample]=e}}else{n.sort(((t,e)=>t.value-e.value));for(const t of n)t.rank=Ys(t.value,n),r[t.sample]=t}return r}(r,o,l);e.send({sample2rank:c})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}}(t,e,0,r,o);if(t.query.ifsamplehasvcf)return function(t,e,n,r,s){if(t.query.iscustom)return e.send({no:1});if(!s.vcf_querykey)return e.send({yes:1});const o=r.queries[s.vcf_querykey];if(!o)return e.send({error:"vcf query missing"});e.send(o.singlesamples?{yes:1}:{no:1})}(t,e,0,r,o);if(!t.query.rglst)return e.send({error:"rglst missing"});if(o.viewrangeupperlimit){if(t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>=o.viewrangeupperlimit)return e.send({error:"zoom in under "+P.bplen(o.viewrangeupperlimit)+" to view details"})}t.query.hiddendt&&(i=new Set(t.query.hiddendt));if(t.query.hiddenmattr){a={};for(const e in t.query.hiddenmattr)a[e]=new Set(t.query.hiddenmattr[e])}if(t.query.filteralleleattr){l={};for(const e in t.query.filteralleleattr){const n=t.query.filteralleleattr[e];n.cutoffvalue,l[e]=n}}if(t.query.filterlocusattr){c={};for(const e in t.query.filterlocusattr){const n=t.query.filterlocusattr[e];n.cutoffvalue,c[e]=n}}if(t.query.sampleset){const e=new Set,n=new Map;for(const r of t.query.sampleset)for(const t of r.samples)e.add(t),n.set(t,r.name);e.size&&(u={set:e,sample2group:n})}if(t.query.hiddensampleattr){f={};for(const e in t.query.hiddensampleattr)f[e]=new Set(t.query.hiddensampleattr[e])}if(o.url)try{o.dir=await F.d1(o.url,o.indexURL)}catch(t){return e.send({error:"svcnv file index url error"})}const d=await function(t,e,n,r,o,i,a){if(!e.file&&!e.url)return[];const l=[];for(const c of n.query.rglst){const u=new Promise(((l,u)=>{const f=[],d=(0,q.spawn)(vs,[e.file?y().join(s().tpmasterdir,e.file):e.url,c.chr+":"+c.start+"-"+c.stop],{cwd:e.dir});O().createInterface({input:d.stdout}).on("line",(e=>{const s=e.split("\t"),l=Number.parseInt(s[1]),c=Number.parseInt(s[2]);let 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t.cohort.sampleAttribute.attributes){t.cohort.sampleAttribute.attributes[e].clientnoshow||n.push(e)}for(const r of e.samplegroups)for(const s of r.samples){const r=t.cohort.annotation[s.samplename];if(r){const t={};let o=!1;for(const e of n){const n=r[e];null!=n&&(o=!0,t[e]=n)}o&&(e.sampleannotation[s.samplename]=t)}}}})(r,w),e.send(w)})),ks.post(qs+"/mdsgenecount",(async function(t,e){try{const n=bs[t.query.genome];if(!n)throw"invalid genome";if(!n.datasets)throw"no datasets from genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.gene2mutcount)throw"not supported on this dataset";if(!t.query.samples)throw".samples missing";let s,o;s=t.query.selectedMutTypes?t.query.selectedMutTypes.join("+"):"total",o=t.query.nGenes?t.query.nGenes:15;const i=`WITH\n\tfiltered AS (\n\t\tSELECT gene, ${s} AS total FROM genecount\n\t\tWHERE sample IN (${JSON.stringify(t.query.samples).replace(/[[\]\"]/g,"").split(",").map((t=>"'"+t+"'")).join(",")})\n\t)\n\tSELECT gene, SUM(total) AS count\n\tFROM filtered\n\tGROUP BY gene\n\tORDER BY count DESC\n\tLIMIT ${o}`,a=r.gene2mutcount.db.prepare(i).all(),l=[];for(const t of a){const e=n.genedb.getCoordByGene.get(t.gene);e&&(e.gene=t.gene,e.count=t.count,delete e.name,l.push(e))}e.send({genes:l})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),ks.post(qs+"/mds2",function(t){return async(e,n)=>{const r=e.query;try{const e=t[r.genome],s=await async function(t,e){if(!e)throw"invalid genome";if(t.dslabel){const n=e.datasets[t.dslabel];if(!n)throw"invalid dslabel";if(!n.track)throw"no mds2 track found for dataset";return n}const n={iscustom:1,track:{}};t.vcf&&(n.track.vcf=t.vcf,await F._H(n.track.vcf,e));t.ld;return n}(r,e);if(r.trigger_overlayld)return await async function(t,e,n){if(!t.ldtkname)throw".ldtkname missing";const r=e.track.ld.tracks.find((e=>e.name==t.ldtkname));if(!r)throw"ld tk not found by name: "+t.ldtkname;const s=t.m.ref+"."+t.m.alt,o=(r.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+t.m.pos+"-"+(t.m.pos+1),i=[];await F.UE({args:[r.file,o],dir:r.dir,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),a=n[3],l=n[4],c=Number.parseFloat(n[5]);r==t.m.pos&&a==s?i.push({pos:o,alleles:l,r2:c}):o==t.m.pos&&l==s&&i.push({pos:r,alleles:a,r2:c})}}),n.send({lst:i})}(r,s,n);r.hidden_mclass&&(r.hidden_mclass=new Set(r.hidden_mclass));const o={mclass2count:{}};if(r.info_fields){o.info_fields={};for(const t of r.info_fields)if(t.iscategorical)o.info_fields[t.key]={value2count:{}};else if(t.isnumerical)o.info_fields[t.key]={filteredcount:0};else{if(!t.isflag)throw"unknown info type";o.info_fields[t.key]={count_yes:0,count_no:0}}}if(r.trigger_mafcovplot&&await async function(t,e,n,r){try{if(!n.track)throw"ds.track missing";const e=n.track.vcf;if(!e)throw"ds.track.vcf missing";if(n.iscustom)e.plot_mafcov={show_samplename:1};else if(!e.plot_mafcov)throw"maf-cov plot is not supported 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r.plotgroups)for(const e of t.lst){const t=s.get(e.sampleobj.name);if(t){const n=o(t);e.sampleobj.color=n,i.has(t)||i.set(t,{count:0,color:n,label:t}),i.get(t).count++}else a++,e.sampleobj.color=Zr}if(r.categories=[],e.CTE1&&e.CTE1.name2bin)for(const t of e.CTE1.name2bin.keys()){const e=i.get(t);e&&r.categories.push(e)}else for(const[t,e]of i)r.categories.push(e);a&&r.categories.push({count:a,color:Zr,label:"Unannotated"})}}catch(t){r.error=t.message||t,t.stack&&console.log(t.stack)}}(r,0,s,o),r.trigger_vcfbyrange&&(await Rr(r,0,s,o),r.trigger_ld)){o.__mposset=new Set;for(const t of o.vcf.rglst)if(t.variants)for(const e of t.variants)o.__mposset.add(e.pos)}if(r.trigger_ld){o.ld={};for(const t of r.trigger_ld.tracks)await Br(t,r,0,s,o);delete o.__mposset}r.trigger_ssid_onevcfm&&await async function(t,e,n,r){if(n.iscustom)throw"custom ds not allowed";const s=n.track.vcf;if(!s)throw"ds.track.vcf missing";if(!t.m)throw"q.m missing";const o=(s.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+(t.m.pos+1)+"-"+(t.m.pos+1),i=s.chr2bcffile[t.m.chr];if(!i)throw"chr not in chr2bcffile";let a;if(await F.UE({isbcf:!0,args:["query",i,"-r",o,"-f",Ir+"\t%FORMAT\n"],dir:s.dir,callback:e=>{const[n,r,o]=D.S(e,s);for(const e of r)if(e.pos==t.m.pos&&e.ref==t.m.ref&&e.alt==t.m.alt)return void(a=e)}}),!a)throw"variant not found";const l=[],c=[],u=[];for(const e of a.sampledata){if(!e.genotype)continue;const n=-1!=e.genotype.indexOf(t.m.ref),r=-1!=e.genotype.indexOf(t.m.alt);n?r?c.push(e.sampleobj.name):l.push(e.sampleobj.name):r&&u.push(e.sampleobj.name)}const f=Math.random().toString();r.ssid=f,r.groups={};const d=[];if(l.length){const t="Homozygous reference";r.groups[t]={size:l.length},d.push(t+"\t"+l.join(","))}if(c.length){const t="Heterozygous";r.groups[t]={size:c.length},d.push(t+"\t"+c.join(","))}if(u.length){const t="Homozygous alternative";r.groups[t]={size:u.length},d.push(t+"\t"+u.join(","))}await F.Sf(y().join(Or.cachedir_ssid,f),d.join("\n"))}(r,0,s,o),r.trigger_getvcfcsq&&await async function(t,e,n,r){const s=n.track.vcf;if(!s)throw"ds.track.vcf missing";if(!t.m)throw"q.m missing";const o=(s.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+(t.m.pos+1)+"-"+(t.m.pos+1),i=s.chr2bcffile[t.m.chr];if(!i)throw"chr not in chr2bcffile";await F.UE({isbcf:!0,args:["query",i,"-r",o,"-f",Ir+"\\n"],dir:s.dir,callback:e=>{const[n,o,i]=D.S(e,s);for(const e of o)if(e.pos==t.m.pos&&e.ref==t.m.ref&&e.alt==t.m.alt)return void(r.csq=e.csq)}})}(r,0,s,o),n.send(o)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}}(bs)),ks.post(qs+"/mdsexpressionrank",(function(t,e){let n,r,o,i=new Set;Promise.resolve().then((()=>{if(!t.query.rglst)throw"rglst missing";if(t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>1e7)throw"Zoom in below 10 Mb to show expression rank";if(!t.query.sample)throw"sample missing";if(t.query.iscustom){if(n=bs[t.query.genome],!n)throw"invalid genome";if(!t.query.file&&!t.query.url)throw"no file or url for expression data";r={},o={file:t.query.file,url:t.query.url,indexURL:t.query.indexURL}}else{const[e,s,i,a]=Rs(t.query);if(e)throw e;if(n=s,r=i,o=a,!o.samples)throw"total samples missing from server config";if(-1==o.samples.indexOf(t.query.sample))throw{nodata:1}}if(o.viewrangeupperlimit&&t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>o.viewrangeupperlimit)throw"zoom in under "+P.bplen(o.viewrangeupperlimit)+" to view data";if(t.query.levelkey){if(!t.query.levelvalue)throw"levelvalue is required when levelkey is used";if(!r.cohort||!r.cohort.annotation)throw".cohort.annotation missing from dataset"}if(!o.file){if(!o.url)throw"file or url missing";return F.d1(o.url,o.indexURL)}})).then((e=>{const n=[];for(const a of t.query.rglst)n.push(new Promise(((n,l)=>{const c=(0,q.spawn)(vs,[o.file?y().join(s().tpmasterdir,o.file):o.url,a.chr+":"+a.start+"-"+a.stop],{cwd:e}),u=O().createInterface({input:c.stdout}),f=new Map;u.on("line",(e=>{const n=e.split("\t"),s=JSON.parse(n[3]);if(!s.gene)return;if(!s.sample)return;if(!Number.isFinite(s.value))return;const o=n[0],a=Number.parseInt(n[1]),l=Number.parseInt(n[2]);if(s.sample==t.query.sample)return f.has(s.gene)||f.set(s.gene,{chr:o,start:a,stop:l,allvalues:[]}),f.get(s.gene).thisvalue=s.value,void(s.ase&&(f.get(s.gene).ase=s.ase));if(t.query.attributes){const e=r.cohort.annotation[s.sample];if(!e)return;for(const n of t.query.attributes)if(n.k&&n.kvalue&&n.kvalue!=e[n.k])return}i.add(s.sample),f.has(s.gene)||f.set(s.gene,{chr:o,start:a,stop:l,allvalues:[]}),f.get(s.gene).allvalues.push({value:s.value})}));const d=[];c.stderr.on("data",(t=>d.push(t))),c.on("close",(t=>{const e=d.join("");e&&!gs(e)&&l({message:e}),n(f)}))})));return Promise.all(n)})).then((t=>{const n=[];for(const e of t)for(const[t,r]of e)null!=r.thisvalue&&(r.allvalues.sort(((t,e)=>t.value-e.value)),r.rank=Ys(r.thisvalue,r.allvalues),delete r.allvalues,r.gene=t,n.push(r));e.send({result:n,samplecount:i.size})})).catch((t=>{t.stack&&console.log(t),t.nodata?e.send({nodata:1}):e.send({error:t.message?t.message:t})}))})),ks.post(qs+"/mdsgeneboxplot",(t=>async(e,n)=>{try{const[r,o,i,a]=function(t,e){if(!e.query.gene)throw"gene name missing";if(!e.query.chr)throw"chr missing";if(!Number.isInteger(e.query.start))throw"start missing";if(!Number.isInteger(e.query.stop))throw"stop missing";const n=t[e.query.genome];if(!n)throw"invalid genome";let r,s,o;if(e.query.iscustom){if(!e.query.file&&!e.query.url)throw"no file or url for expression data";r={},s={file:e.query.file,url:e.query.url,indexURL:e.query.indexURL}}else{if(!n.datasets)throw"genome is not equipped with datasets";if(!e.query.dslabel)throw"dslabel missing";if(r=n.datasets[e.query.dslabel],!r)throw"invalid dslabel";if(!r.queries)throw"dataset is not equipped with queries";if(!e.query.querykey)throw"querykey missing";if(s=r.queries[e.query.querykey],!s)throw"invalid querykey"}if(e.query.svcnv)if(o={},e.query.iscustom)o.dsquery={file:e.query.svcnv.file,url:e.query.svcnv.url,indexURL:e.query.svcnv.indexURL};else{e.query.svcnv.genome=e.query.genome;const t=n.datasets[e.query.svcnv.dslabel];if(!t)throw"invalid dslabel";if(!t.queries)throw"dataset is not equipped with queries";if(!e.query.svcnv.querykey)throw"querykey missing";const r=t.queries[e.query.svcnv.querykey];if(!r)throw"invalid querykey";o.ds=t,o.dsquery=r}if(e.query.getgroup)if(e.query.sampleset);else{if(!r.cohort||!r.cohort.annotation)throw"no sample annotation for getting group";if(e.query.getgroup_unannotated){if(!s.boxplotbysamplegroup)throw"dsquery.boxplotbysamplegroup{} missing when getgroup_unannotated"}else{if(!Array.isArray(e.query.getgroup))throw"getgroup should be array";for(const t of e.query.getgroup){if(!t.k)throw"k missing from one of getgroup";if(!t.kvalue)throw"kvalue missing from one of getgroup"}}}return[n,r,s,o]}(t,e);e.query.getalllst,n.send(await async function(t,e,n,r,o){n.url&&(n.dir=await F.d1(n.url,n.indexURL));r&&r.dsquery.url&&(r.dsquery.dir=await F.d1(r.dsquery.url,r.dsquery.indexURL));const i=function(t){if(!t.query.sampleset)return;const e=new Map;for(const n of t.query.sampleset)for(const t of n.samples)e.set(t,n.name);return e}(o),a=new Map,l=[],c=[];if(await F.UE({args:[n.file?y().join(s().tpmasterdir,n.file):n.url,o.query.chr+":"+o.query.start+"-"+o.query.stop],dir:n.dir,callback:t=>{const r=t.split("\t"),s=JSON.parse(r[3]);if(s.gene&&s.gene==o.query.gene&&Number.isFinite(s.value))if(o.query.getalllst)l.push({sample:s.sample,value:s.value});else if(o.query.getgroup){if(!s.sample)return;if(i)return void(o.query.getgroup_unannotated?i.has(s.sample)||c.push(s):i.get(s.sample)==o.query.getgroup[0].full&&c.push(s));const t=e.cohort.annotation[s.sample];if(o.query.getgroup_unannotated){if(!t)return void c.push(s);for(const e of n.boxplotbysamplegroup.attributes)if(null==t[e.k])return void c.push(s);return}if(!t)return;for(const e of o.query.getgroup)if(e.kvalue!=t[e.k])return;c.push(s)}else if(n.boxplotbysamplegroup&&e.cohort&&e.cohort.annotation){if(!s.sample)return;let t;t=null==o.query.index_boxplotgroupers||0==o.query.index_boxplotgroupers?n.boxplotbysamplegroup.attributes:n.boxplotbysamplegroup.additionals[o.query.index_boxplotgroupers-1].attributes;const r=e.cohort.annotation[s.sample];if(!r)return void l.push({sample:s.sample,value:s.value});const i=r[t[0].k];if(null==i)return void l.push({sample:s.sample,value:s.value});const c=[];for(let e=1;e<t.length;e++){const n=r[t[e].k];if(null==n)break;c.push(n)}c.unshift(i);const u=c.join(", ");if(!a.has(u)){const e={samples:[],attributes:[]};for(const n of t){const t=r[n.k];if(null==t)break;const s={k:n.k,kvalue:t};n.full&&(s.full=n.full,s.fullvalue=r[n.full]),e.attributes.push(s)}a.set(u,e)}a.get(u).samples.push({sample:s.sample,value:s.value})}else if(i){if(!s.sample)return;const t=i.get(s.sample);if(!t)return void l.push({sample:s.sample,value:s.value});a.has(t)||a.set(t,{samples:[],attributes:[{full:t}]}),a.get(t).samples.push({sample:s.sample,value:s.value})}else l.push({sample:s.sample,value:s.value})}}),o.query.getgroup2boxplot){c.sort(((t,e)=>t.value-e.value));const{w1:t,w2:e,p25:n,p50:r,p75:s,out:o}=F.JC(c);return{n:c.length,min:c[0].value,max:c[c.length-1].value,w1:t,w2:e,p25:n,p50:r,p75:s,out:o}}const u=[];for(const[t,e]of a)u.push({name:t,values:e.samples,attributes:e.attributes});l.length&&u.push({name:"Unannotated",values:l});c.length&&u.push({values:c});if(o.query.getalllst)return{lst:u[0].values};if(o.query.iscustom&&!i||1==u.length){if(u[0]){const t=u[0].values;return t.sort(((t,e)=>e.value-t.value)),{lst:t,max:t[0].value,min:t[t.length-1].value}}return{nodata:1}}const f=await async function(t,e){if(!e||!t.query.svcnv.useloss&&!t.query.svcnv.usegain&&!t.query.svcnv.usesv)return;let n=t.query.start,r=t.query.stop;t.query.svcnv.usesv&&Number.isInteger(t.query.svcnv.svflank)&&(n=Math.max(0,n-t.query.svcnv.svflank),r+=t.query.svcnv.svflank);const o=new Map;return await F.UE({args:[e.dsquery.file?y().join(s().tpmasterdir,e.dsquery.file):e.dsquery.url,t.query.chr+":"+n+"-"+r],dir:e.dsquery.dir,callback:e=>{const n=e.split("\t"),r=JSON.parse(n[3]);if(r.sample)if(r.chrA||r.chrB){if(!t.query.svcnv.usesv)return;o.has(r.sample)||o.set(r.sample,{}),o.get(r.sample).sv=1}else{if(!t.query.svcnv.usegain&&!t.query.svcnv.useloss)return;if(t.query.svcnv.usesv&&t.query.svcnv.svflank){const e=Number.parseInt(n[1]),r=Number.parseInt(n[2]);if(Math.max(t.query.start,e)>Math.min(t.query.stop,r))return}if(!Number.isFinite(r.value))return;if(!t.query.svcnv.usegain&&r.value>0)return;if(!t.query.svcnv.useloss&&r.value<0)return;if(t.query.svcnv.valueCutoff&&Math.abs(r.value)<t.query.svcnv.valueCutoff)return;if(t.query.svcnv.bplengthUpperLimit&&Number.parseInt(n[2])-Number.parseInt(n[1])>t.query.svcnv.bplengthUpperLimit)return;o.has(r.sample)||o.set(r.sample,{}),r.value>0?o.get(r.sample).gain=1:r.value<0&&(o.get(r.sample).loss=1)}}}),o}(o,r);if(o.query.getgroup){if(u[0]){const t=u[0].values;if(t.sort(((t,e)=>e.value-t.value)),f)for(const e of t){const t=f.get(e.sample);if(t)for(const n in t)e[n]=t[n]}return{lst:t,max:t[0].value,min:t[t.length-1].value}}return{nodata:1}}const d=[];let h=null,p=null;for(const t of u){t.values.sort(((t,e)=>t.value-e.value));const e=t.values.length;null==h?(h=t.values[0].value,p=t.values[e-1].value):(h=Math.min(h,t.values[0].value),p=Math.max(p,t.values[e-1].value));const{w1:n,w2:r,p25:s,p50:i,p75:a,out:l}=F.JC(t.values),c=[{isall:1,w1:n,w2:r,p25:s,p50:i,p75:a,out:l}];if(f){if(o.query.svcnv.usegain){const e=t.values.filter((t=>f.has(t.sample)&&f.get(t.sample).gain));if(e.length){const{w1:t,w2:n,p25:r,p50:s,p75:o,out:i}=F.JC(e);c.push({iscnvgain:1,samplecount:e.length,w1:t,w2:n,p25:r,p50:s,p75:o,out:i})}}if(o.query.svcnv.useloss){const e=t.values.filter((t=>f.has(t.sample)&&f.get(t.sample).loss));if(e.length){const{w1:t,w2:n,p25:r,p50:s,p75:o,out:i}=F.JC(e);c.push({iscnvloss:1,samplecount:e.length,w1:t,w2:n,p25:r,p50:s,p75:o,out:i})}}if(o.query.svcnv.usesv){const e=t.values.filter((t=>f.has(t.sample)&&f.get(t.sample).sv));if(e.length){const{w1:t,w2:n,p25:r,p50:s,p75:o,out:i}=F.JC(e);c.push({issv:1,samplecount:e.length,w1:t,w2:n,p25:r,p50:s,p75:o,out:i})}}}d.push({name:t.name+" ("+t.values.length+")",boxplots:c,attributes:t.attributes})}return d.sort(((t,e)=>t.name<e.name?-1:t.name>e.name?1:0)),{groups:d,min:h,max:p}}(0,o,i,a,e))}catch(t){t.stack&&console.log(t),n.send({error:t.message||t})}})(bs)),ks.post(qs+"/mdsgenevalueonesample",(async function(t,e){const n=t.query;try{if(!n.sample)throw".sample missing";if(!n.genes)throw".genes[] missing";let r,o,i;if(t.query.iscustom){if(r=bs[n.genome],!r)throw"invalid genome";if(!n.file&&!n.url)throw"no file or url for expression data";o={},i={file:n.file,url:n.url,indexURL:n.indexURL}}else{const[t,e,s,a]=Rs(n);if(t)throw t;r=e,o=s,i=a}const a=i.file?null:await F.d1(i.url,i.indexURL),l={};let c=!0;for(const t of n.genes){let e;await F.UE({args:[i.file?y().join(s().tpmasterdir,i.file):i.url,t.chr+":"+t.start+"-"+t.stop],dir:a,callback:r=>{const s=r.split("\t");if(!s[3])return;const o=JSON.parse(s[3]);o.gene==t.gene&&o.sample==n.sample&&(e=o.value)}}),Number.isFinite(e)&&(l[t.gene]=e,c=!1)}c?e.send({nodata:1}):e.send({result:l})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),ks.post(qs+"/vcf",(async function(t,e){try{const[n,r,s]=F.ZX(t);if(n)throw n;const o=s?await F.d1(r,t.query.indexURL):null;if(!t.query.rglst)throw"rglst missing";const i=[];for(const e of t.query.rglst)await F.UE({args:[r,e.chr+":"+e.start+"-"+e.stop],dir:o,callback:t=>i.push(t)});e.send({linestr:i.join("\n")})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),ks.get(qs+"/vcfheader",(async function(t,e){try{if(!t.query.genome)throw"genome missing";const n=bs[t.query.genome];if(!n)throw"invalid genome";const[r,s,o]=F.ZX(t);if(r)throw r;const i=o?await F.d1(s,t.query.indexURL):null;e.send({metastr:(await F.ZD(s,i)).join("\n"),nochr:await F.Jy(s,i,n)})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),ks.post(qs+"/translategm",(async function(t,e){try{const n=bs[t.query.genome];if(!n)throw"invalid genome";const r=t.query.gm;if(!r)throw"missing gm{}";if(!r.chr)throw"gm.chr missing";if(!r.start)throw"gm.start missing";if(!Number.isInteger(r.start))throw"gm.start not integer";if(!r.stop)throw"gm.stop missing";if(!Number.isInteger(r.stop))throw"gm.stop not integer";const s=await F.Kf(n,r.chr+":"+(r.start+1)+"-"+r.stop),o=P.fasta2gmframecheck(r,s);e.send({frame:o})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),ks.post(qs+"/samplematrix",(function(t,e){Promise.resolve().then((()=>{const e=bs[t.query.genome];if(!e)throw"invalid genome";let n,r;if(t.query.iscustom){if(!t.query.querykey2tracks)throw"querykey2tracks{} missing for custom dataset";n={queries:{}};for(const e in t.query.querykey2tracks){const r=t.query.querykey2tracks[e];if(!r.type)throw'missing "type" for a data track';if(r.type==P.tkt.mdsvcf){const r=t.query.querykey2tracks[e];r.type=P.mdsvcftype.vcf,n.queries[e]={type:P.tkt.mdsvcf,info:r.info,tracks:[r]}}else if(r.type==P.tkt.mdssvcnv)n.queries[e]=r;else{if(r.type!=P.tkt.mdsexpressionrank)throw"unknown type of data track: "+r.type;n.queries[e]=r}}}else{if(!e.datasets)throw"genome is not equipped with datasets";if(!t.query.dslabel)throw"dslabel missing";if(n=e.datasets[t.query.dslabel],!n)throw"invalid dslabel";if(!n.queries)throw"dataset is not equipped with queries"}if(t.query.sampleset)r=new Set(t.query.sampleset);else if(t.query.limitsamplebyeitherannotation){if(!n.cohort)throw"limitsamplebyeitherannotation but no cohort in ds";if(!n.cohort.annotation)throw"limitsamplebyeitherannotation but no cohort.annotation in ds";r=new Set;for(const e in n.cohort.annotation){const s=n.cohort.annotation[e];for(const n of t.query.limitsamplebyeitherannotation)if(s[n.key]==n.value){r.add(e);break}}}const s=[];for(const e of t.query.features){let t,o=[];if(e.querykey){if(!n.queries)throw"using querykey for a feature but no ds.queries";if(t=n.queries[e.querykey],!t)throw"unknown dsquery by key "+e.querykey}else if(e.querykeylst){if(!n.queries)throw"using querykeylst for a feature but no ds.queries";for(const t of e.querykeylst){const e=n.queries[t];if(!e)throw'unknown key "'+t+'" from querykeylst';o.push(e)}if(0==o.length)throw"no valid keys in querykeylst"}else if(!e.issampleattribute)throw"unknown way to query a feature";if(e.isgenevalue){const[o,i]=Xs(e,n,t,r);if(o)throw"error with isgenevalue: "+o;s.push(i)}else if(e.iscnv){const[o,i]=Qs(e,n,t,r);if(o)throw"error with iscnv: "+o;s.push(i)}else if(e.isloh){const[o,i]=to(e,n,t,r);if(o)throw"error with isloh: "+o;s.push(i)}else if(e.isvcf){const[o,i]=oo(e,n,t,r);if(o)throw"error with isvcf: "+o;s.push(i)}else if(e.isitd){const[o,i]=eo(e,n,t,r);if(o)throw"error with isitd: "+o;s.push(i)}else if(e.issvfusion){const[o,i]=no(e,n,t,r);if(o)throw"error with issvfusion: "+o;s.push(i)}else if(e.issvcnv){const[o,i]=ro(e,n,t,r);if(o)throw"error with issvcnv: "+o;s.push(i)}else if(e.ismutation){const[t,i]=so(e,n,o,r);if(t)throw"error with ismutation: "+t;s.push(i)}else{if(!e.issampleattribute)throw"unknown type of feature";{const[t,o]=Ks(e,n,r);if(t)throw"error with issampleattribute: "+t;s.push(o)}}}return Promise.all(s)})).then((t=>{e.send({results:t})})).catch((t=>{e.send({error:"string"==typeof t?t:t.message}),t.stack&&console.error(t.stack)}))})),ks.get(qs+"/mdssamplescatterplot",(async function(t,e){try{const n=bs[t.query.genome];if(!n)throw"invalid genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.cohort)throw"no cohort for dataset";if(!r.cohort.annotation)throw"cohort.annotation missing for dataset";const s=r.cohort.scatterplot;if(!s)throw"scatterplot not supported for this dataset";const o=[];for(const e in r.cohort.annotation){const n=r.cohort.annotation[e];if(t.query.subsetkey&&n[t.query.subsetkey]!=t.query.subsetvalue)continue;const i=n[s.x.attribute];if(!Number.isFinite(i))continue;const a=n[s.y.attribute];Number.isFinite(a)&&o.push({sample:e,x:i,y:a,s:n})}e.send({colorbyattributes:s.colorbyattributes,colorbygeneexpression:s.colorbygeneexpression,querykey:s.querykey,dots:o,tracks:s.tracks})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),ks.post(qs+"/mdssamplesignature",(function(t,e){try{const n=t.query;if(!n.sample)throw".sample missing";const r=bs[n.genome];if(!r)throw"invalid genome";const s=r.datasets[n.dslabel];if(!s)throw"invalid dataset";if(!s.cohort)throw"no cohort for dataset";if(!s.cohort.mutation_signature)throw"no mutation_signature for cohort";const o=[];for(const t in s.cohort.mutation_signature.sets){const e=s.cohort.mutation_signature.sets[t];if(!e.samples)continue;const r=e.samples.map.get(n.sample);if(!r)continue;const i=[];for(const t in e.signatures)r[t]&&i.push({k:t,v:r[t]});i.length&&o.push({key:t,valuename:e.samples.valuename,annotation:i.sort(((t,e)=>e.v-t.v))})}e.send({lst:o})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),ks.post(qs+"/mdssurvivalplot",function(t){return async(e,n)=>{try{const r=e.query,s=t[r.genome];if(!s)throw"invalid genome";const o=s.datasets[r.dslabel];if(!o)throw"invalid dataset";if(!o.cohort)throw"no cohort for dataset";if(!o.cohort.annotation)throw"cohort.annotation missing for dataset";const i=o.cohort.survivalplot;if(!i)throw"survivalplot not supported for this dataset";if(!i.plots)throw".plots{} missing";if(e.query.init)return void n.send(i.init);if(!r.type)throw".type missing";const a=i.plots[r.type];if(!a)throw"unknown plot type: "+r.type;const l=function(t,e,n){if(!t.samplerule)throw".samplerule missing";if(!t.samplerule.full)throw".samplerule.full missing";const r=[];if(t.samplerule.full.byattr){const n=t.samplerule.full.key;if(!n)throw"key missing from samplerule.full{}";const s=t.samplerule.full.value;if(null==s)throw"value missing from samplerule.full{}";for(const t in e.cohort.annotation){const o=e.cohort.annotation[t];o[n]==s&&r.push({name:t,o})}}else if(t.samplerule.full.useall)for(const t in e.cohort.annotation){const n=e.cohort.annotation[t];r.push({name:t,o:n})}else{if(!t.samplerule.full.usesampleset)throw"unknown rule for samplerule.full";{const n=t.samplerule.full.sampleset;for(const t in n){const s=n[t],o=e.cohort.annotation[s];null!=o&&r.push({name:s,o})}}}const s=[];for(const t of r)Number.isFinite(t.o[n.serialtimekey])&&(t.serialtime=t.o[n.serialtimekey],t.censored=t.o[n.iscensoredkey],s.push(t));if(0==s.length)throw"no samples found for full set";return s}(r,o,a),c=await async function(t,e,n,r){if(e.samplerule.mutated_sets){const n=new Set(t.map((t=>t.name))),r=e.samplerule.mutated_sets.reduce(((e,r)=>{const s=new Set(r.samplenames);r.lst=t.filter((t=>s.has(t.name)));for(const t of r.samplenames)n.delete(t);return delete r.samplenames,e.push(r),e}),[]);return r.push({name:"No mutation (n="+n.size+")",lst:t.filter((t=>n.has(t.name))),is_notmutated:!0}),r}const s=e.samplerule.set;if(!s)return[{name:"All",lst:t}];if(s.geneexpression){if(!s.gene)throw".gene missing from samplerule.set";if(!s.chr)throw".chr missing from samplerule.set";if(!Number.isInteger(s.start))throw".start not integer from samplerule.set";if(!Number.isInteger(s.stop))throw".start not integer from samplerule.set";if(s.bymedian)return await async function(t,e,n,r){const s=e.samplerule.set,[o,i]=await is(t,e,n),a=Math.ceil(i.length/2),l=i[a-1].genevalue;return[{name:s.gene+" "+o.datatype+" below median (n="+a+", value<"+l+")",lst:i.slice(0,a)},{name:s.gene+" "+o.datatype+" above median (n="+(i.length-a)+", value>="+l+")",lst:i.slice(a,i.length)}]}(t,e,n);if(s.byquartile)return await async function(t,e,n,r){const s=e.samplerule.set,[o,i]=await is(t,e,n),a=Math.ceil(.25*i.length),l=Math.ceil(.5*i.length),c=Math.ceil(.75*i.length),u=i[a-1].genevalue,f=i[l-1].genevalue,d=i[c-1].genevalue;return[{name:s.gene+" "+o.datatype+" from 1st quartile (n="+a+", value<"+u+")",lst:i.slice(0,a),isfirstquartile:!0},{name:s.gene+" "+o.datatype+" from 2nd quartile (n="+(l-a)+", "+u+"<=value<"+f+")",lst:i.slice(a,l)},{name:s.gene+" "+o.datatype+" from 3rd quartile (n="+(c-l)+", "+f+"<=value<"+d+")",lst:i.slice(l,c)},{name:s.gene+" "+o.datatype+" from 4th quartile (n="+(i.length-c)+", value>="+d+")",lst:i.slice(c,i.length),isfourthquartile:!0}]}(t,e,n)}if(s.mutation){if(!s.chr)throw".chr missing from samplerule.set";if(!Number.isInteger(s.start))throw".start not integer from samplerule.set";if(!Number.isInteger(s.stop))throw".start not integer from samplerule.set";return await async function(t,e,n){const r=e.samplerule.set;if(r.samples_snvindel=new Set,r.samples_cnv=new Set,r.samples_loh=new Set,r.samples_sv=new Set,r.samples_fusion=new Set,r.samples_itd=new Set,r.cnv&&!r.snvindel&&!r.loh&&!r.sv&&!r.fusion&&!r.itd){const[r,s]=await rs(t,e,n,!0),o=[],i=[],a=[];for(const e of t)r.has(e.name)?o.push(e):s.has(e.name)?i.push(e):a.push(e);const l=[];return i.length&&l.push({name:"Copy number loss (n="+i.length+")",lst:i}),o.length&&l.push({name:"Copy number gain (n="+o.length+")",lst:o}),a.length&&l.push({name:"No copy number variation (n="+a.length+")",lst:a}),l}const s=await rs(t,e,n),o=[];for(const e of t)s.find((t=>t.name==e.name))||o.push(e);const i=[];s.length&&i.push({name:"With mutation (n="+s.length+")",lst:s});o.length&&i.push({name:"No mutation (n="+o.length+")",lst:o});return i}(t,e,n)}throw"unknown rule for samplerule.set{}"}(l,r,o);let u;c.length>1&&(u=await ns(c)),await async function(t,e){if(!t.samplerule.mutated_sets)return;const n=e.find((t=>t.is_notmutated));if(!n)return;for(const t of e){if(t.is_notmutated)continue;const e=await ns([t,n]);t.pvalue=e}}(r,c),await async function(t,e){if(!t.samplerule.set)return;if(!t.samplerule.set.geneexpression)return;if(!t.samplerule.set.byquartile)return;if(4!=e.length)return;if(t.samplerule.set.against1st){for(let t=1;t<4;t++)e[t].pvalue=await ns([e[0],e[t]]);return}if(t.samplerule.set.against4th){for(let t=0;t<3;t++)e[t].pvalue=await ns([e[t],e[3]]);return}}(r,c);for(const t of c)as(t),delete t.lst;const f={samplesets:c,pvalue:u};r.samplerule.set&&r.samplerule.set.mutation&&(f.count_snvindel=r.samplerule.set.samples_snvindel.size,f.count_cnv=r.samplerule.set.samples_cnv.size,f.count_loh=r.samplerule.set.samples_loh.size,f.count_sv=r.samplerule.set.samples_sv.size,f.count_fusion=r.samplerule.set.samples_fusion.size,f.count_itd=r.samplerule.set.samples_itd.size),n.send(f)}catch(t){t.stack&&console.error(t.stack),n.send({error:t.message||t})}}}(bs)),ks.post(qs+"/fimo",function(t){return async(e,n)=>{try{const r=e.query;if(!r.m)throw"no mutation";if(!r.m.chr)throw"mutation chr 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s=r.split("\n"),o=s.slice(1).join("");return s[0]+"\n"+o.substr(0,t.pos-e)+("-"==t.alt?"":t.alt)+o.substr(t.pos-e+("-"==t.ref?0:t.ref.length))}(t.m,n,0,s),l=await Qr(t,e,a);for(const t of l){t.pvalue_alt=t.pvalue,delete t.pvalue,t.logpvalue_alt=t.logpvalue,delete t.logpvalue,i.has(t.name)||i.set(t.name,[]);let e=!0;for(const n of i.get(t.name))if(null!=n.logpvalue_ref&&n.strand==t.strand&&Math.abs(t.start-n.start)<=2&&Math.abs(t.stop-n.stop)<=2){n.pvalue_alt=t.pvalue_alt,n.logpvalue_alt=t.logpvalue_alt,n.logpvaluediff=t.logpvalue_alt-n.logpvalue_ref,n.logpvaluediff>0?n.gain=!0:n.loss=!0,e=!1;break}e&&i.get(t.name).push(t)}let c=0,u=0;const f=[];for(const e of i.values())for(const n of e)null==n.logpvaluediff&&(null==n.pvalue_ref?(n.gain=!0,n.logpvaluediff=n.logpvalue_alt):null==n.pvalue_alt&&(n.loss=!0,n.logpvaluediff=-n.logpvalue_ref)),null!=t.minabslogp&&Math.abs(n.logpvaluediff)<t.minabslogp||(n.logpvaluediff>0?c=Math.max(c,n.logpvaluediff):u=Math.min(u,n.logpvaluediff),f.push(n));return{items:f,valuemin:u,valuemax:c,refstart:n,refstop:r,refseq:s.split("\n").slice(1).join("")}}(r,s);n.send(o)}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}(bs)),ks.all(qs+"/termdb",X.TO(bs)),ks.all(qs+"/termdb-barsql",ot.TO(bs)),ks.post(qs+"/singlecell",function(t){return async(e,n)=>{try{const r=e.query,s=t[r.genome];if(!s)throw"invalid genome";if(r.getpcd)return void await async function(t,e){const n={},r=await async function(t,e){if(!t.textfile)throw".textfile missing";{const[e,n,r]=F.ZX({query:{file:t.textfile}});if(e)throw".textfile error: "+e;if(!r){if(await F.yE(n))throw"file not exist: "+t.textfile;if(await F.t7(n))throw"file not readable: "+t.textfile}t.textfile=n}let n,r,s,o,i;if(t.getpcd.category_autocolor){const e=t.getpcd.values_count&&t.getpcd.values_count<=10?zr.Z:Wr;n=$r.Z(e),s={},o={}}else if(t.getpcd.category_customcolor){const e=$r.Z(Wr);a=t.getpcd.cat_values,l=e,n=t=>{let e=!1;for(const n of a)if(n.value==t)return e=!0,n.color;if(!e)return l(t)},s={},o={},i={}}else if(t.getpcd.gene_expression){const n=t.getpcd.gene_expression;if(!n.file)throw"gene_expression.file missing";{const[t,e,r]=F.ZX({query:{file:n.file}});if(t)throw t;n.file=e}if(!Number.isInteger(n.barcodecolumnidx))throw"gene_expression.barcodecolumnidx missing";if(!n.chr)throw"gene_expression.chr missing";if(!n.start)throw"gene_expression.start missing";if(!n.stop)throw"gene_expression.stop missing";if(!n.genename)throw"gene_expression.genename missing";if(!n.autoscale)throw"gene_expression: unknown scaling method";if(!n.color_min)throw"gene_expression.color_min missing at autoscale";if(!n.color_max)throw"gene_expression.color_max missing at autoscale";const s=(n.nochr?n.chr.replace("chr",""):n.chr)+":"+n.start+"-"+n.stop,o=new Map;r=new Map;let i=0,a=0;if(e.numbercellwithgeneexp=0,e.numbercelltotal=0,await F.UE({args:[n.file,s],callback:t=>{const r=JSON.parse(t.split("\t")[3]);r.gene==n.genename&&Number.isFinite(r.value)&&(e.numbercellwithgeneexp++,n.autoscale&&(i=Math.min(i,r.value),a=Math.max(a,r.value)),o.set(r.sample,r.value))}}),n.autoscale){e.minexpvalue=i,e.maxexpvalue=a;const t=bt.ZP(n.color_min,n.color_max);for(const[e,n]of o){const s=tt.ZP(t((n-i)/(a-i)));r.set(e,Number.parseInt(Yr(s.r,s.g,s.b),16))}}}var a,l;return new Promise(((i,a)=>{const l=[],c=O().createInterface({input:m().createReadStream(t.textfile)});let u=!0,f=0,d=0;c.on("line",(i=>{if(u)return void(u=!1);const a=i.split(t.delimiter),c=[];for(const e of t.getpcd.coord)c.push(a[e]),f=Math.max(f,a[e]),d=Math.min(d,a[e]);if(2==t.getpcd.coord.length&&c.push("0"),n){const e=a[t.getpcd.category_index],r=n(e);if(t.hidden_types.includes(e))if(t.background_color){const e=tt.ZP(t.background_color),n=Number.parseInt(Yr(e.r,e.g,e.b),16);c.push(n)}else c.push(16777215);else c.push(Number.parseInt(r.slice(1),16));s&&(s[e]=r),o&&(o[e]=e in o?o[e]+1:1)}else if(r){e.numbercelltotal++;const n=a[t.getpcd.gene_expression.barcodecolumnidx];let s=r.get(n);if(void 0===s)if(t.getpcd.gene_expression.color_no_exp){const e=tt.ZP(t.getpcd.gene_expression.color_no_exp);s=Number.parseInt(Yr(e.r,e.g,e.b),16)}else s="2894892";c.push(s)}l.push(c.join(" "))})),c.on("close",(()=>{s&&(t.getpcd.category_customorder&&(s=function(t,e){let n={};const r=Object.keys(t).length;for(var s=1;s<=r;s++){const r=e.find((t=>{if(t.order==s)return t.value}));r&&(n[r.value]=t[r.value])}for(const r of e)r.order||(n[r.value]=t[r.value]);for(const r in t){e.find((t=>{if(t.value==JSON.stringify(r))return!0}))||(n[r]=t[r])}return n}(s,t.getpcd.cat_values)),e.category2color=s,e.categorycount=o),e.data_sphere_r=Math.max(Math.abs(f),Math.abs(d)),i(l)}))}))}(t,n),s="# .PCD v.7 - Point Cloud Data file format\nVERSION .7\nFIELDS x y z rgb\nSIZE 4 4 4 4\nTYPE F F F F\nCOUNT 1 1 1 1\nWIDTH 1200\nHEIGHT 800\nVIEWPOINT 0 0 0 1 0 0 0\nPOINTS 960000\nDATA ascii\n";n.pcddata=s+r.join("\n"),e.send(n)}(r,n);if(r.getgeneboxplot)return void await async function(t,e,n){const r=t.getgeneboxplot,s=t.getgeneboxplot.values_count&&t.getgeneboxplot.values_count<=10?$r.Z(zr.Z):$r.Z(Wr);if(!r.expfile)throw"getgeneboxplot.expfile missing";{const[t,e,n]=F.ZX({query:{file:r.expfile}});if(t)throw"getgeneboxplot.expfile error: "+t;r.expfile=e}if(!r.chr)throw"getgeneboxplot.chr missing";if(!r.start)throw"getgeneboxplot.start missing";if(!r.stop)throw"getgeneboxplot.stop missing";if(!r.genename)throw"getgeneboxplot.genename missing";const o=await Kr(r),i=(r.nochr?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;let a=0,l=0;await F.UE({args:[r.expfile,i],callback:t=>{const e=JSON.parse(t.split("\t")[3]);if(e.gene!=r.genename)return;if(!e.sample)return;if(!Number.isFinite(e.value))return;const n=o.get(e.sample);n&&(n.expvalue=e.value,a=Math.min(a,e.value),l=Math.max(l,e.value))}});const c=new Map;for(const[t,e]of o)c.has(e.category)||c.set(e.category,[]),r.exclude_cells&&0==parseInt(e.expvalue)||c.get(e.category).push({value:e.expvalue});const u=[],f=(d=Fn.Z().domain([a,l]).ticks(20),t=>{const e=[];for(let t=1;t<d.length;t++)e.push(0);for(const n of t)for(let t=1;t<d.length;t++)if(n.value<=d[t]){e[t-1]++;break}return e});var d;for(const[t,e]of c){e.sort(((t,e)=>t.value-e.value));const n=F.JC(e);delete n.out;const r=s(t);n.category=t,n.color=r,n.numberofcells=e.length,n.density=f(e),u.push(n)}let h=[];if(t.getgeneboxplot.cat_values){const e=Object.keys(t.getgeneboxplot.cat_values).length;for(var p=1;p<=e;p++){const e=t.getgeneboxplot.cat_values.find((t=>{if(t.order==p)return t.value}));e&&h.push(u.filter((t=>t.category==e.value))[0])}for(const e of t.getgeneboxplot.cat_values)e.order||h.push(u.filter((t=>t.category==e.value))[0]);for(const e of u){t.getgeneboxplot.cat_values.find((t=>{if(t.value==e.category)return!0}))||h.push(e)}for(const e of h){const n=t.getgeneboxplot.cat_values.find((t=>{if(t.value==e.category)return t}));n&&n.color&&(e.color=n.color)}}else h=u;n.send({boxplots:h,minexpvalue:a,maxexpvalue:l})}(r,0,n);if(r.getheatmap)return void await async function(t,e,n){const r=t.getheatmap,s=[];if(!r.expfile)throw"getgeneboxplot.expfile missing";{const[t,e,n]=F.ZX({query:{file:r.expfile}});if(t)throw"getgeneboxplot.expfile error: "+t;r.expfile=e}r.gene_list.forEach((t=>{if(!t.chr)throw"getgeneboxplot.chr missing";if(!t.start)throw"getgeneboxplot.start missing";if(!t.stop)throw"getgeneboxplot.stop missing";if(!t.gene)throw"getgeneboxplot.genename missing"}));const o=await Kr(r);for(const t of r.gene_list){const e=(t.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop;let n=0,i=0;const a=t.gene;await F.UE({args:[r.expfile,e],callback:e=>{const r=JSON.parse(e.split("\t")[3]);if(r.gene.toUpperCase()!==t.gene.toUpperCase())return;if(!r.sample)return;if(!Number.isFinite(r.value))return;const s=o.get(r.sample);s&&(s.expvalue=r.value,n=Math.min(n,r.value),i=Math.max(i,r.value))}});const l=new Map;for(const[t,e]of o)l.has(e.category)||l.set(e.category,[]),l.get(e.category).push({value:e.expvalue});const c=[];for(const[t,e]of l){let n=0;for(const t of e)n+=t.value;const r=e.length,s=(n/r).toFixed(3);c.push({category:t,mean:s,numberofcells:r})}s.push({genename:a,heatmap:c})}n.send({gene_heatmap:s})}(r,0,n)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}}(bs)),ks.post(qs+"/massSession",(async function(t,e){try{const n=t.body.__sessionFor__,{filename:r,route:o,dslabel:i,embedder:a}=n||{};let l;if(r){const e={headers:t.headers,query:n};if(l=Jr.i.getPayloadFromHeaderAuth(e,o),!l.email)throw"invalid credentials: no jwt.email";if(l.dslabel!=i||l.route!=o||l.embedder!=a)throw"invalid credentials: mismatched payload";delete t.body.__sessionFor__}const c=r||function(){const t=[];for(;t.length<15;){const e=46+Math.floor(80*Math.random());(e>=48&&e<=57||e>=65&&e<=90||e>=97&&e<=122)&&t.push(String.fromCharCode(e))}return t.join("")}(),u=JSON.stringify(t.body),f=r?Hr(n,l):s().cachedir_massSession;await m().promises.access(f).then((()=>!0)).catch((()=>!1))||m().mkdirSync(f,{recursive:!0}),await F.Sf(y().join(f,c),u),e.send({id:c})}catch(t){e.send({error:t.message||t})}})),ks.get(qs+"/massSession",(async function(t,e){try{const n=t.query.id;if(!n)throw"session id missing";const{route:r,dslabel:o,embedder:i}=t.query,a=t.query.route?Jr.i.getPayloadFromHeaderAuth(t,t.query.route):null,l=t.query.route?Hr(t.query,a):s().cachedir_massSession,c=y().join(l,n);let u;try{u=(await m().promises.stat(c)).birthtime}catch(t){throw"invalid session"}const f=await F.b5(c),d=JSON.parse(f);if(t.query.route)return void e.send({state:d});const h=new Date,p=new Date(u),g=s().features.massSessionDuration||30,b=g-Math.round((h.getTime()-p.getTime())/864e5);e.send({state:d,sessionDaysLeft:b,massSessionDuration:g})}catch(t){e.send({error:t.message||t})}})),ks.delete(qs+"/massSession",(async function(t,e){try{const n=t.query.ids;if(!n)throw"session ids[] missing";const{route:r,dslabel:o,embedder:i}=t.query,a=t.query.route?Jr.i.getPayloadFromHeaderAuth(t,t.query.route):null;if(!a)throw"missing credentials";const l=t.query.route?Hr(t.query,a):s().cachedir_massSession,c=[];for(const t of n){const e=y().join(l,t);m().unlink(e,(t=>{if(t)throw c.push(t),t}))}c.length||e.send({status:"ok"})}catch(t){e.send({error:t.message||t})}})),ks.get(qs+"/sessionIds",(async function(t,e){try{const{filename:n,route:r,dslabel:s,embedder:o}=t.query,i=Jr.i.getPayloadFromHeaderAuth(t,r);if(!i.email)throw"invalid credentials: no jwt.email";if(i.dslabel!=s||i.route!=r||i.embedder!=o)throw"invalid credentials: mismatched payload";const a=Hr(t.query,i);if(!await m().promises.access(a).then((()=>!0)).catch((()=>!1)))return void e.send({status:"ok",sessionIds:[]});const l=await m().promises.readdir(a);e.send({status:"ok",sessionIds:l})}catch(t){e.status(401),e.send({error:t.message||t})}})),ks.get(qs+"/isoformbycoord",(async function(t,e){try{const n=bs[t.query.genome];if(!n)throw"invalid genome";if(!t.query.chr)throw"chr missing";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos must be positive integer";const o=n.tracks.find((t=>t.__isgene));o||reject("no gene track");const i=[];await F.UE({args:[y().join(s().tpmasterdir,o.file),t.query.chr+":"+r+"-"+r],callback:t=>{const e=t.split("\t")[3];if(!e)return;const r=JSON.parse(e);if(!r.isoform)return;const s={isoform:r.isoform},o=n.genedb.getjsonbyisoform.get(r.isoform);o&&(s.name=JSON.parse(o.genemodel).name,s.isdefault=o.isdefault),i.push(s)}}),e.send({lst:i})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),ks.post(qs+"/ase",(async function(t,e){const n=t.query,r=3e6,o=5e5;try{const t=bs[n.genome];if(!t)throw"invalid genome";if(!n.samplename)throw"samplename missing";if(!n.chr)throw"no chr";if(!n.start||!n.stop)throw"no start/stop";if(!n.rnabarheight)throw"no rnabarheight";if(!n.dnabarheight)throw"no dnabarheight";if(!Number.isInteger(n.barypad))throw"invalid barypad";if(n.rnamax&&!Number.isFinite(n.rnamax))throw"invalid value for rnamax";if(!n.checkrnabam)throw".checkrnabam{} missing";const i=Us(n.checkrnabam);if(i)throw i;if(n.refcolor||(n.refcolor="blue"),n.altcolor||(n.altcolor="red"),!t.tracks)throw"genome.tracks[] missing";const a=t.tracks.find((t=>t.__isgene));if(!a)throw"no gene track from this genome";await async function(t,e){if(t.rnabamfile)t.rnabamfile=y().join(s().tpmasterdir,t.rnabamfile);else{if(!t.rnabamurl)throw"no file or url for rna bam";t.rnabamurl_dir=await F.d1(t.rnabamurl,t.rnabamindexURL||t.rnabamurl+".bai")}if(t.rnabam_nochr=await F.Dp(t.rnabamfile||t.rnabamurl,e,t.rnabamurl_dir),t.vcffile)t.vcffile=y().join(s().tpmasterdir,t.vcffile);else{if(!t.vcfurl)throw"no file or url for vcf";t.vcfurl_dir=await F.d1(t.vcfurl,t.vcfindexURL)}t.vcf_nochr=await F.Jy(t.vcffile||t.vcfurl,t.vcfurl_dir,e)}(n,t);const l=await Hs(t,a,n.chr,n.start,n.stop),c={};if(n.stop-n.start<r)for(const[t,e]of l){const t={file:n.rnabamfile,url:n.rnabamurl,dir:n.rnabamurl_dir,nochr:n.rnabam_nochr};let r;r=n.rnabamispairedend?await Ds(t,n.chr,e):await Ps(t,n.chr,e),e.fpkm=1e9*r/(n.rnabamtotalreads*e.exonlength)}else c.fpkmrangelimit=r;const[u,f,d,h]=function(t,e){let n=t.start,r=t.stop;for(const[t,s]of e)n=Math.min(n,s.start),r=Math.max(r,s.stop);const s=t.start,o=t.stop;return[n,r,s,o]}(n,l),p=await async function(t,e,n,r,s){const o=await Vs(t.vcffile||t.vcfurl,t.vcfurl_dir),[i,a,l,c]=D.e(o);if(c)throw c;const u={info:i,format:a,samples:l},f=await Ws(t.vcffile||t.vcfurl,(t.vcf_nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+s,t.vcfurl_dir),d=[];for(const e of f||[]){const[n,r,s]=D.S(e,u);for(const e of r){if(!P.basecolor[e.ref]||!P.basecolor[e.alt])continue;if(!e.sampledata)continue;const n=Js(e,t.samplename,t.checkrnabam);n&&d.push(n)}}const h=[];for(const t of d)for(const[e,r]of n)if(t.pos>=r.start&&t.pos<=r.stop){h.push(t);break}return h}(n,0,l,u,f);for(const t of p)t.rnacount={nocoverage:1};let g,b;h-d>=o?c.covplotrangelimit=o:(n.rnamax?g=n.rnamax:(g=await async function(t,e,n){let r=0;return await F.UE({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl||t.rnabamfile],dir:t.rnabamurl_dir,callback:t=>{const e=t.split("\t");if(3!=e.length)return;const n=Number.parseInt(e[2]);Number.isInteger(n)&&(r=Math.max(r,n))}}),r}(n,d,h),c.rnamax=g),b=await async function(t,e,n,r,s){const o=new Map;for(const t of r)t.dnacount.ishet&&t.pos>=e&&t.pos<=n&&o.set(t.pos,t);const i=(0,S.createCanvas)(t.width*t.devicePixelRatio,(t.rnabarheight+t.barypad+t.dnabarheight)*t.devicePixelRatio),a=i.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio);let l,c,u=!1;n-e<=t.width?(u=!0,l=1,c=t.width/(n-e),a.lineWidth=c):(c=1,l=(n-e)/t.width);return await F.UE({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl||t.rnabamfile],dir:t.rnabamurl_dir,callback:n=>{const r=n.split("\t");if(3!=r.length)return;const i=Number.parseInt(r[1])-1;if(!Number.isInteger(i))return;const f=Number.parseInt(r[2]);if(!Number.isInteger(f))return;const d=t.rnabarheight*Math.min(f,s)/s,h=u?(i-e)*c:(i-e)/l;a.strokeStyle="#ccc",a.beginPath(),a.moveTo(h+c/2,t.rnabarheight),a.lineTo(h+c/2,t.rnabarheight-d),a.stroke(),a.closePath(),f>s&&(a.strokeStyle="blue",a.beginPath(),a.moveTo(h+c/2,0),a.lineTo(h+c/2,2),a.stroke(),a.closePath());const p=o.get(i);p&&(p.rnacount.h=d)}}),{canvas:i,ctx:a,isbp:u,binpxw:c,binbpsize:l}}(n,d,h,p,g)),c.coveragesrc=await function(t,e,n,r,s,o,i,a){const l=[];for(const n of e)n.dnacount.ishet&&l.push((t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(n.pos+1)+"-"+(n.pos+1));return new Promise(((n,r)=>{const c=(0,q.spawn)(_s,["mpileup","-q",t.checkrnabam.rnapileup_q,"-Q",t.checkrnabam.rnapileup_Q,"--no-reference","-a","INFO/AD","-d",999999,"-r",l.join(","),t.rnabamurl||t.rnabamfile],{cwd:t.rnabamurl_dir});O().createInterface({input:c.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Gs(t);if(!n)return;let r;n.pos>=s&&n.pos<=o&&n.DP;const i=e.find((t=>t.pos==n.pos));if(i){i.__x=r;const t=n.allele2count[i.ref]||0,e=n.allele2count[i.alt]||0;t+e>0&&(delete i.rnacount.nocoverage,i.rnacount.ref=t,i.rnacount.alt=e,i.rnacount.f=e/(t+e))}})),c.on("close",(()=>{if(!i)return void n();const{canvas:r,ctx:l,binpxw:c}=i;l.lineWidth=Math.max(3,c);let u=0;for(const n of e)n.dnacount&&(n.pos<s||n.pos>o||(n.__x=t.width*(n.pos-s)/(o-s),u=Math.max(u,n.dnacount.ref+n.dnacount.alt)));for(const n of e){if(null==n.__x)continue;n.rnacount.nocoverage||(null==n.rnacount.h&&(n.rnacount.h=t.rnabarheight*(n.rnacount.ref+n.rnacount.alt)/a),l.strokeStyle=t.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight),l.lineTo(n.__x+c/2,t.rnabarheight-(1-n.rnacount.f)*n.rnacount.h),l.stroke(),l.closePath(),l.strokeStyle=t.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight-(1-n.rnacount.f)*n.rnacount.h),l.lineTo(n.__x+c/2,t.rnabarheight-n.rnacount.h),l.stroke(),l.closePath());const e=t.dnabarheight*(n.dnacount.ref+n.dnacount.alt)/u;n.dnacount.ishet&&(l.strokeStyle=t.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight+t.barypad),l.lineTo(n.__x+c/2,t.rnabarheight+t.barypad+(1-n.dnacount.f)*e),l.stroke(),l.closePath(),l.strokeStyle=t.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight+t.barypad+(1-n.dnacount.f)*e),l.lineTo(n.__x+c/2,t.rnabarheight+t.barypad+e),l.stroke(),l.closePath()),delete n.__x}n(r.toDataURL())}))}))}(n,p,0,0,d,h,b,g),await async function(t,e){if(0==t.length)return;const n=[];for(const r of t)r.rnacount.nocoverage||r.rnacount.ref+r.rnacount.alt<e.checkrnabam.rna_mintotalreads||n.push(r);if(0==n.length)return;const r=await function(t){const e=y().join(s().cachedir,Math.random().toString())+".snp",n=[];for(const e of t)e.rnacount.nocoverage||null!=e.rnacount.ref&&null!=e.rnacount.alt&&n.push(e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt);return new Promise(((t,r)=>{m().writeFile(e,n.join("\n")+"\n",(n=>{n&&r("cannot write"),t(e)}))}))}(n),o=await Bs(r);await function(t,e){return new Promise(((n,r)=>{m().readFile(e,"utf8",((e,s)=>{e&&r("cannot read binom pvalue"),s||n();for(const e of s.trim().split("\n")){const n=e.split("\t"),r=t.find((t=>n[0]==t.pos+"."+t.ref+"."+t.alt));r&&(r.rnacount.pvalue=Number.parseFloat(n[10]))}n()}))}))}(t,o),m().unlink(r,(()=>{})),m().unlink(o,(()=>{}))}(p,n),c.genes=function(t,e,n){const r=[];for(const[s,o]of e){r.push(o);const e=t.filter((t=>t.pos>=o.start&&t.pos<=o.stop));if(0==e.length){o.nosnp=1;continue}o.snps=e;const s=e.filter((t=>null!=t.rnacount.pvalue));if(0==s.length){o.nornasnp=1;continue}const i=s.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let a=null,l=0;for(const t of s)null==a?a=t.rnacount.pvalue:a*=t.rnacount.pvalue,t.rnacount.pvalue<=n.checkrnabam.binompvaluecutoff&&l++;o.ase={markers:e.filter((t=>t.dnacount.ishet)).length,ase_markers:l,mean_delta:i/s.length,geometricmean:Math.pow(a,1/s.length)}}return r}(p,l,n);let v=0;for(const t of p)t.dnacount&&t.pos>=d&&t.pos<=h&&(v=Math.max(v,t.dnacount.ref+t.dnacount.alt));c.dnamax=v,e.send(c)}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),ks.post(qs+"/bamnochr",(async function(t,e){const n=t.query;try{const t=bs[n.genome];if(!t)throw"invalid genome";if(n.file)n.file=y().join(s().tpmasterdir,n.file);else{if(!n.url)throw"no bam file or url";n.url_dir=await F.d1(n.url,n.indexURL||n.url+".bai")}const r=await F.Dp(n.file||n.url,t,n.url_dir);e.send({nochr:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),ks.get(qs+"/gene2canonicalisoform",(function(t,e){try{if(!t.query.gene)throw".gene missing";const n=bs[t.query.genome];if(!n)throw"unknown genome";if(!n.genedb.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const r=n.genedb.get_gene2canonicalisoform.get(t.query.gene);e.send(r)}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),ks.get(qs+"/ideogram",(function(t,e){try{const n=bs[t.query.genome];if(!n)throw"invalid genome";if(!n.genedb.hasIdeogram)throw"ideogram not supported on this genome";if(!t.query.chr)throw".chr missing";const r=n.genedb.getIdeogramByChr.all(t.query.chr);if(!r.length)throw"no ideogram data for this chr";e.send(r)}catch(t){e.send({error:t.message||t})}}));F.lY,F.ZX;function ao(t){const e=t.split(/\r?\n/);if(e.length<=1||!e[0])return[null,[]];const n=e[0].split("\t"),r=[];for(let t=1;t<e.length;t++){if("#"==e[t][0])continue;const s=e[t].split("\t"),o={};for(let t=0;t<n.length;t++){const e=s[t];e&&(o[n[t]]=e)}r.push(o)}return[null,r]}async function lo(t){try{await m().promises.stat(t.tpmasterdir)}catch(e){const n="Error with "+t.tpmasterdir+": "+e.code;if("validate"==process.argv[2])throw n;return void console.log("\n!!! "+n+"\n")}if(function(){if(s().features.skip_checkDependenciesAndVersions)return void console.log("SKIPPED checkDependenciesAndVersions()");const t=["jsonlite","cmprsk","hwde","lmtest"];for(const e of t){const t=N().spawnSync(s().Rscript,["-e",`suppressPackageStartupMessages(library("${e}"))`],{encoding:"utf8"});if(t.stderr.trim())throw t.stderr}const e=10;{const t=N().execSync(s().samtools+" --version",{encoding:"utf8"}).trim().split("\n"),[n,r]=t[0].split(" ");if("samtools"!=n||!r)throw'cannot run "samtools version"';const[o,i]=r.split(".");if("1"!=o)throw"samtools not 1.*";if(Number(i)<e)throw`samtools not >= 1.${e}`}{const t=N().execSync(s().bcftools+" -v",{encoding:"utf8"}).trim().split("\n"),[n,r]=t[0].split(" ");if("bcftools"!=n||!r)throw'cannot run "bcftools version"';const[o,i]=r.split(".");if("1"!=o)throw"bcftools not 1.*";if(Number(i)<e)throw`bcftools not >= 1.${e}`}}(),null!=t.base_zindex){const e=Number.parseInt(t.base_zindex);if(Number.isNaN(e)||e<=0)throw"base_zindex must be positive integer";t.base_zindex=e}if(t.jwt){if(!t.jwt.secret)throw"jwt.secret missing";if(!t.jwt.permissioncheck)throw"jwt.permissioncheck missing"}if(!t.tpmasterdir)throw".tpmasterdir missing";if(!t.cachedir)throw".cachedir missing";if(t.cachedir_massSession=await fo("massSession"),t.cachedir_massSessionTrash=await fo("massSessionTrash"),t.cache_snpgt={dir:await fo("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},t.cachedir_bam=await fo("bam"),t.cachedir_genome=await fo("genome"),t.cachedir_ssid=await fo("ssid"),t.commonOverrides&&P.applyOverrides(t.commonOverrides),!t.genomes)throw".genomes[] missing";if(!Array.isArray(t.genomes))throw".genomes[] not array";for(const e of t.genomes){if(!e.name)throw".name missing from a genome: "+JSON.stringify(e);if(!e.file)throw".file missing from genome "+e.name;const n=y().join(process.cwd(),e.file),r=require(m().existsSync(n)?n:e.file),s=r.default||r;if(bs[e.name]=s,!s.genomefile)throw".genomefile missing from .js file of genome "+e.name;if("NA"==s.genomefile||(s.genomefile=y().join(t.tpmasterdir,s.genomefile)),s.genomicNameRegexp||(s.genomicNameRegexp=/[^a-zA-Z0-9.:_-]/),s.tracks||(s.tracks=[]),e.tracks)for(const t of e.tracks)s.tracks.push(t);if(e.datasets&&(s.rawdslst=e.datasets),e.snp&&(s.snp=e.snp),e.blat){if(!e.blat.host)throw".blat.host missing for "+e.name;if(!e.blat.port)throw".blat.port missing for "+e.name;s.blat=e.blat}if(e.nosnp&&delete s.snp,e.nohicenzyme&&delete s.hicenzymefragment,e.nohicdomain&&delete s.hicdomain,s.genedb&&e.no_gene2canonicalisoform&&delete s.genedb.gene2canonicalisoform,e.updateAttr)for(const t of e.updateAttr){let e=s;for(const[n,r]of t.entries())if(e)if("object"==typeof r)for(const t in r)e[t]=r[t];else{if("string"==typeof e[r]){t[n+1]&&(e[r]=t[n+1]);break}e=e[r]}}}t.defaultgenome&&bs[t.defaultgenome]&&(bs[t.defaultgenome].isdefault=!0);for(const e in bs){const n=bs[e];if(!n.majorchr)throw e+": majorchr missing";if(!n.defaultcoord)throw e+": defaultcoord missing";if(await F.Kf(n,n.defaultcoord.chr+":"+n.defaultcoord.start+"-"+(n.defaultcoord.start+1)),n.tracks||(n.tracks=[]),"string"==typeof n.majorchr){const t=n.majorchr.trim().split(/[\s\t\n]+/),r={},s=[];for(let n=0;n<t.length;n+=2){const o=t[n],i=Number.parseInt(t[n+1]);if(Number.isNaN(i))throw e+" majorchr invalid chr size for "+o+" ("+t[n+1]+")";r[o]=i,s.push(o)}n.majorchr=r,n.majorchrorder=s}n.chrlookup={};for(const t in n.majorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.majorchr[t],major:!0};if(n.minorchr){if("string"==typeof n.minorchr){const t=n.minorchr.trim().split(/[\s\t\n]+/),r={};for(let n=0;n<t.length;n+=2){const s=Number.parseInt(t[n+1]);if(Number.isNaN(s))throw e+" minorchr invalid chr size for "+t[n]+" ("+t[n+1]+")";r[t[n]]=s}n.minorchr=r}for(const t in n.minorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.minorchr[t]}}if(n.genedb){if(!n.genedb.dbfile)throw e+": .genedb.dbfile missing";try{console.log("Connecting",n.genedb.dbfile),n.genedb.db=F.sE(n.genedb.dbfile)}catch(t){throw`Cannot connect genedb: ${n.genedb.dbfile}: ${t}`}n.genedb.getnamebynameorisoform=n.genedb.db.prepare("select name from genes where name=? or isoform=?"),n.genedb.getnamebyisoform=n.genedb.db.prepare("select distinct name from genes where isoform=?"),n.genedb.getjsonbyname=n.genedb.db.prepare("select isdefault,genemodel from genes where name=?"),n.genedb.getjsonbyisoform=n.genedb.db.prepare("select isdefault,genemodel from genes where isoform=?"),n.genedb.getnameslike=n.genedb.db.prepare("select distinct name from genes where name like ? limit 20");const t=(0,Kn.jj)(n.genedb.db);t.has("genealias")&&(n.genedb.getNameByAlias=n.genedb.db.prepare("select name from genealias where alias=?"),n.genedb.getAliasByName=n.genedb.db.prepare("select alias from genealias where name=?")),t.has("gene2coord")&&(n.genedb.getCoordByGene=n.genedb.db.prepare("select * from gene2coord where name=?")),t.has("ideogram")?(n.genedb.hasIdeogram=!0,n.genedb.getIdeogramByChr=n.genedb.db.prepare("select * from ideogram where chromosome=?")):n.genedb.hasIdeogram=!1,t.has("gene2canonicalisoform")&&(n.genedb.get_gene2canonicalisoform=n.genedb.db.prepare("select isoform from gene2canonicalisoform where gene=?")),t.has("buildDate")&&(n.genedb.get_buildDate=n.genedb.db.prepare("select date from buildDate")),n.genedb.hasTable_refseq2ensembl=t.has("refseq2ensembl"),n.genedb.sqlTables=[...t],n.genedb.tableSize={};for(const e of t)"buildDate"!=e&&(n.genedb.tableSize[e]=n.genedb.db.prepare(`select count(*) as size from ${e}`).get().size)}if(n.termdbs)for(const t in n.termdbs)(0,Kn.JV)(n.termdbs[t],ys),console.log(`${t} initiated as ${e}-level termdb`);for(const e of n.tracks)if(e.__isgene){if(!e.file)throw"Tabix file missing for gene track: "+JSON.stringify(e);try{await F.LC(y().join(t.tpmasterdir,e.file))}catch(t){throw"Error with "+e.file+": "+t}}if(n.proteindomain){if(!n.proteindomain.dbfile)throw e+".proteindomain: missing dbfile for sqlite db";if(!n.proteindomain.statement)throw e+".proteindomain: missing statement for sqlite db";let t;try{console.log("Connecting",n.proteindomain.dbfile),t=F.sE(n.proteindomain.dbfile)}catch(t){throw"Error with "+n.proteindomain.dbfile+": "+t}n.proteindomain.getbyisoform=t.prepare(n.proteindomain.statement)}if(n.snp){if(!n.snp.bigbedfile)throw e+".snp: missing bigBed file";n.snp.bigbedfile=y().join(t.tpmasterdir,n.snp.bigbedfile),await F.Ic(n.snp.bigbedfile)}if(n.fimo_motif){if(!n.fimo_motif.db)throw e+".fimo_motif: db file missing";if(n.fimo_motif.db=y().join(t.tpmasterdir,n.fimo_motif.db),n.fimo_motif.annotationfile){const[e,r]=ao(m().readFileSync(y().join(t.tpmasterdir,n.fimo_motif.annotationfile),{encoding:"utf8"}).trim());n.fimo_motif.tf2attr={};for(const t of r)n.fimo_motif.tf2attr[t.Model.split("_")[0]]=t}}if(n.hicenzymefragment){if(!Array.isArray(n.hicenzymefragment))throw"hicenzymefragment should be an array";for(const e of n.hicenzymefragment){if(!e.enzyme)throw".enzyme missing for one element of hicenzymefragment[]";if(!e.file)throw".file missing for one element of hicenzymefragment[]";try{await F.LC(y().join(t.tpmasterdir,e.file))}catch(t){throw"Error with "+e.file+": "+t}}}if(n.hicdomain){if(!n.hicdomain.groups)throw".groups{} missing from hicdomain";for(const e in n.hicdomain.groups){const r=n.hicdomain.groups[e];if(!r.name)throw".name missing from hicdomain "+e;if(!r.sets)throw".set{} missing from hicdomain "+e;for(const n in r.sets){const s=r.sets[n];if(!s.name)throw".name missing from hicdomain "+e+" > "+n;if(!s.file)throw".file missing from hicdomain "+e+" > "+n;s.file=y().join(t.tpmasterdir,s.file);try{await F.LC(s.file)}catch(t){throw"Error with "+s.file+": "+t}}}}if(n.rawdslst){n.datasets={};for(const t of n.rawdslst){if(t.skip)continue;if(!t.name)throw"a nameless dataset from "+e;if(n.datasets[t.name])throw e+" has duplicating dataset name: "+t.name;if(!t.jsfile)throw"jsfile not available for dataset "+t.name+" of "+e;const r=y().join(process.cwd(),t.jsfile),s=require(m().existsSync(r)?r:t.jsfile),o="function"==typeof s?s(P):"function"==typeof s?.default?s.default(P):s.default||s;if(Xn(o,t),o.noHandleOnClient=t.noHandleOnClient,o.label=t.name,o.genomename=e,n.datasets[o.label]=o,o.isMds3)try{await cr(o,n,0,ks,qs)}catch(t){throw t.stack&&console.log(t.stack),"Error with mds3 dataset "+o.label+": "+t}else if(o.isMds)try{await po(o,n,t)}catch(t){throw"Error with mds dataset "+o.label+": "+t}else uo(o,n)}co(),delete n.rawdslst}}}async function co(){const t=await m().promises.readdir(s().cachedir_massSession);try{t.forEach((async t=>{const e=(await m().promises.stat(y().join(s().cachedir_massSession,t))).birthtime,n=new Date,r=new Date(e),o=s().features.massSessionDuration||30;Math.round((n.getTime()-r.getTime())/864e5)>o&&(await m().promises.copyFile(y().join(s().cachedir_massSession,t),y().join(s().cachedir_massSessionTrash,t)),await m().promises.unlink(y().join(s().cachedir_massSession,t)),console.log("File deleted: ",t,e))}))}catch(t){throw`Error: ${t}`}}function uo(t,e){if(t.dbfile)try{console.log("Connecting",t.dbfile),t.newconn=F.sE(t.dbfile)}catch(e){throw"Error with "+t.dbfile+": "+e}if(t.snvindel_attributes)for(const e of t.snvindel_attributes)if(e.lst)for(const t of e.lst)t.get=t.get.toString();else e.get=e.get.toString();if(t.cohort){if(t.cohort.levels){if(!Array.isArray(t.cohort.levels))throw"cohort.levels must be array for "+t.genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+t.genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+t.genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+t.genomename+"."+t.label;const e=t.newconn.prepare(t.cohort.fromdb.sql).all();delete t.cohort.fromdb,t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.files){let e=[];for(const n of t.cohort.files){if(!n.file)throw".file missing from one of cohort.files[] for "+t.genomename+"."+t.label;const r=m().readFileSync(y().join(s().tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+t.genomename+"."+t.label;e=[...e,...H.tJ(r)]}delete t.cohort.files,t.cohort.raw?t.cohort.raw=[...t.cohort.raw,...e]:t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.tosampleannotation){if(!t.cohort.tosampleannotation.samplekey)throw".samplekey missing from .cohort.tosampleannotation for "+t.genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+t.genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+t.genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=ho(n,t,e);if(r)throw'Error parsing a query in "'+t.label+'": '+r}if(t.vcfinfofilter){const e=P.validate_vcfinfofilter(t.vcfinfofilter);if(e)throw t.label+": vcfinfofilter error: "+e}if(t.url4variant)for(const e of t.url4variant){if(!e.makelabel)throw"makelabel() missing for one item of url4variant from "+t.label;if(!e.makeurl)throw"makeurl() missing for one item of url4variant from "+t.label;e.makelabel=e.makelabel.toString(),e.makeurl=e.makeurl.toString()}}async function fo(t){const e=y().join(s().cachedir,t);try{await m().promises.stat(e)}catch(t){if("ENOENT"!=t.code)throw"error stating dir";try{await m().promises.mkdir(e)}catch(t){throw"cannot make dir"}}return e}function ho(t,e,n){if(!t.name)return".name missing";if(t.dsblocktracklst){if(!Array.isArray(t.dsblocktracklst))return"dsblocktracklst not an array in "+e.label;for(const n of t.dsblocktracklst){if(!n.type)return"missing type for a blocktrack of "+e.label;if(!n.file&&!n.url)return"neither file or url given for a blocktrack of "+e.label}}else if(t.vcffile){const e=N().execSync(vs+" -H "+y().join(s().tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==e)return"no meta lines in VCF file "+t.vcffile+" of query "+t.name;const[r,o,i,a]=D.e(e.split("\n"));if(a)return"error parsing VCF meta lines of "+t.vcffile+": "+a.join("; ");t.vcf={vcfid:Math.random().toString(),info:r,format:o,samples:i},t.hlinfo&&(t.vcf.hlinfo=t.hlinfo,delete t.hlinfo),t.infopipejoin&&(t.vcf.infopipejoin=t.infopipejoin,delete t.infopipejoin);const l=N().execSync(vs+" -l "+y().join(s().tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==l)return"tabix -l found no chromosomes/contigs in "+t.vcffile+" of query "+t.name;t.vcf.nochr=P.contigNameNoChr(n,l.split("\n"));let c=0;if(r)for(const t in r)c++;console.log("Parsed vcf meta from "+t.vcffile+": "+c+" INFO, "+i.length+" sample, "+(t.vcf.nochr?'no "chr"':'has "chr"'))}else{if(!t.makequery)return"do not know how to parse query: "+t.name;if(t.isgeneexpression){if(!t.config)return"config object missing for gene expression query of "+t.name;t.config.maf&&(t.config.maf.get=t.config.maf.get.toString())}}}async function po(t,e,n){if((t.isMds2||t.isMds3||t.isMds)&&Xn(t,n),t.assayAvailability){if(!t.assayAvailability.file)throw".assayAvailability.file missing";if(!t.assayAvailability.assays)throw".assayAvailability.assays[] missing";Object.freeze(t.assayAvailability.assays),t.assayAvailability.samples=new Map;for(const e of m().readFileSync(y().join(s().tpmasterdir,t.assayAvailability.file),{encoding:"utf8"}).trim().split("\n")){const[n,r]=e.split("\t");t.assayAvailability.samples.set(n,JSON.parse(r))}console.log(t.assayAvailability.samples.size+" samples with assay availability ("+t.label+")")}if(t.gene2mutcount){if(!t.gene2mutcount.dbfile)throw".gene2mutcount.dbfile missing";try{console.log("Connecting",t.gene2mutcount.dbfile),t.gene2mutcount.db=F.sE(t.gene2mutcount.dbfile),console.log("DB connected for "+t.label+": "+t.gene2mutcount.dbfile)}catch(e){throw`Error connecting db at ${t.gene2mutcount.dbfile}`}}if(t.sampleAssayTrack){if(!t.sampleAssayTrack.file)throw".file missing from sampleAssayTrack";t.sampleAssayTrack.samples=new Map;let e=0,n=new Set;for(const r of m().readFileSync(y().join(s().tpmasterdir,t.sampleAssayTrack.file),{encoding:"utf8"}).trim().split("\n")){if(!r)continue;if("#"==r[0])continue;const[s,o,i]=r.split("\t");if(!o||!i)continue;if(!t.sampleAssayTrack.samples.has(s)){if(t.cohort&&t.cohort.annotation&&!t.cohort.annotation[s]){n.add(s);continue}t.sampleAssayTrack.samples.set(s,[])}const a=JSON.parse(i);if(!P.tkt[a.type])throw"invalid type from a sample track: "+i;a.name||(a.name=s+" "+o),a.assayName=o,t.sampleAssayTrack.samples.get(s).push(a),e++}console.log(e+" assay-tracks from "+t.sampleAssayTrack.samples.size+" samples ("+t.label+")"),n.size&&console.log("Error: "+n.size+" samples with assay tracks are unannotated: "+[...n].join(" "))}if(t.singlesamplemutationjson){const e=t.singlesamplemutationjson;if(!e.file)throw".file missing from singlesamplemutationjson";e.samples={};let n=0;for(const t of m().readFileSync(y().join(s().tpmasterdir,e.file),{encoding:"utf8"}).trim().split("\n")){if(!t)continue;if("#"==t[0])continue;const[r,s]=t.split("\t");r&&s&&(n++,e.samples[r]=s)}console.log(n+" samples for disco plot")}if(t.cohort&&t.cohort.db&&t.cohort.termdb&&await Tr(t,ks,qs),t.cohort&&t.cohort.files){if(!Array.isArray(t.cohort.files))throw".cohort.files is not array";if(!t.cohort.tohash)throw".tohash() missing from cohort";if("function"!=typeof t.cohort.tohash)throw".cohort.tohash is not function";if(!t.cohort.samplenamekey)throw".samplenamekey missing";if(t.cohort.annotation={},t.cohort.mutation_signature){const e=t.cohort.mutation_signature;if(!e.sets)throw".mutation_signature.sets missing";for(const n in e.sets){const r=e.sets[n];if(r.name||(r.name=n),!r.signatures)throw".signatures{} missing from a signature set";if(r.samples){if(!r.samples.file)throw".samples.file missing from a signature set";const[e,n]=ao(m().readFileSync(y().join(s().tpmasterdir,r.samples.file),{encoding:"utf8"}).trim());r.samples.map=new Map;for(const e of n){const n=e[t.cohort.samplenamekey];if(!n)throw t.cohort.samplenamekey+" missing in file "+r.samples.file;r.samples.map.set(n,e);for(const t in r.signatures)if(e[t]){const s=Number.parseFloat(e[t]);if(Number.isNaN(s))throw"mutation signature value is not float: "+e[t]+" from sample "+n;r.samples.skipzero&&0==s?delete e[t]:e[t]=s}}}}}if(t.cohort.attributes){if(!t.cohort.attributes.lst)throw".lst[] missing for cohort.attributes";if(!Array.isArray(t.cohort.attributes.lst))return".cohort.attributes.lst is not array";for(const e of t.cohort.attributes.lst){if(!e.key)throw".key missing from one of the .cohort.attributes.lst[]";if(!e.label)throw".label missing from one of the .cohort.attributes.lst[]";if(!e.values)throw".values{} missing from "+e.label+" of .cohort.attributes.lst";for(const t in e.values)if(!e.values[t].label)throw".label missing from one value of "+e.label+" in .cohort.attributes.lst"}if(t.cohort.attributes.defaulthidden)for(const e in t.cohort.attributes.defaulthidden){const n=t.cohort.attributes.lst.find((t=>t.key==e));if(!n)throw"invalid defaulthidden key: "+e;for(const r in t.cohort.attributes.defaulthidden[e])if(!n.values[r])throw"invalid defaulthidden value "+r+" for "+e}}if(t.cohort.hierarchies){if(!t.cohort.hierarchies.lst)throw".lst[] missing from .cohort.hierarchies";if(!Array.isArray(t.cohort.hierarchies.lst))throw".cohort.hierarchies.lst is not array";for(const e of t.cohort.hierarchies.lst){if(!e.name)throw".name missing from one hierarchy";if(!e.levels)throw".levels[] missing from one hierarchy";if(!Array.isArray(e.levels))throw".levels is not array from one hierarchy";for(const t of e.levels)if(!t.k)throw".k missing from one level in hierarchy "+e.name}}if(t.cohort.sampleAttribute){if(!t.cohort.sampleAttribute.attributes)throw"attributes{} missing from cohort.sampleAttribute";for(const e in t.cohort.sampleAttribute.attributes){const n=t.cohort.sampleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from cohort.sampleAttribute.attributes";if(n.values)for(const t in n.values){const e=n.values[t];if("object"!=typeof e)throw'value "'+t+'" not pointing to {} from sampleAttribute';e.name||(e.name=t)}if(n.showintrack&&!n.isinteger&&!n.isfloat)throw n.label+": .showintrack requires .isinteger or .isfloat"}}if(t.cohort.scatterplot){if(!t.cohort.sampleAttribute)throw".sampleAttribute missing but required for .cohort.scatterplot";const e=t.cohort.scatterplot;if(!e.querykey)throw".querykey missing from .cohort.scatterplot";{if(!t.queries)throw".cohort.scatterplot.querykey in use but ds.queries{} missing";const n=t.queries[e.querykey];if(!n)throw"unknown query by .cohort.scatterplot.querykey: "+e.querykey;if(n.type!=P.tkt.mdssvcnv)throw"type is not "+P.tkt.mdssvcnv+" of the track pointed to by .cohort.scatterplot.querykey"}if(e.colorbygeneexpression){if(!e.colorbygeneexpression.querykey)throw"querykey missing from .cohort.scatterplot.colorbygeneexpression";if(!t.queries)throw".cohort.scatterplot.colorbygeneexpression in use but ds.queries{} missing";const n=t.queries[e.colorbygeneexpression.querykey];if(!n)throw"unknown query by .cohort.scatterplot.colorbygeneexpression.querykey: "+e.colorbygeneexpression.querykey;if(!n.isgenenumeric)throw"isgenenumeric missing from the track pointed to by .cohort.scatterplot.colorbygeneexpression.querykey"}if(e.tracks,!e.x)throw".x missing from .cohort.scatterplot";if(!e.x.attribute)throw".attribute missing from .cohort.scatterplot.x";const n=t.cohort.sampleAttribute.attributes[e.x.attribute];if(!n)throw"scatterplot.x.attribute is not defined in sampleAttribute";if(!n.isfloat)throw'scatterplot.x is not "isfloat"';if(!e.y)throw".y missing from .cohort.scatterplot";if(!e.y.attribute)throw".attribute missing from .cohort.scatterplot.y";const r=t.cohort.sampleAttribute.attributes[e.y.attribute];if(!r)throw"scatterplot.y.attribute is not defined in sampleAttribute";if(!r.isfloat)throw'scatterplot.y is not "isfloat"';if(e.colorbyattributes)for(const n of e.colorbyattributes){if(!n.key)throw".key missing from one of scatterplot.colorbyattributes";const e=t.cohort.sampleAttribute.attributes[n.key];if(!e)throw"unknown attribute by key "+n.key+" from scatterplot.colorbyattributes";n.label=e.label,n.values=e.values}}for(const e of t.cohort.files){if(!e.file)throw".file missing from one of .cohort.files";const[n,r]=ao(m().readFileSync(y().join(s().tpmasterdir,e.file),{encoding:"utf8"}).trim());if(n)throw'cohort annotation file "'+e.file+'": '+n;console.log(t.label+": "+r.length+" samples loaded from annotation file "+e.file),r.forEach((e=>{for(const n in e){let r;t.cohort.sampleAttribute&&(r=t.cohort.sampleAttribute.attributes[n]),r||t.cohort.termdb&&t.cohort.termdb.termjson&&t.cohort.termdb.termjson.map&&(r=t.cohort.termdb.termjson.map.get(n)),r&&(r.isfloat?e[n]=Number.parseFloat(e[n]):r.isinteger&&(e[n]=Number.parseInt(e[n])))}t.cohort.tohash(e,t)}))}if(t.cohort.annorows=Object.values(t.cohort.annotation),console.log(t.label+": total samples from sample table: "+t.cohort.annorows.length),t.cohort.survivalplot){const e=t.cohort.survivalplot;if(!e.plots)throw".plots{} missing from survivalplot";e.init={plottypes:[]};for(const t in e.plots){const n=e.plots[t];if(!n.name)throw".name missing from survivalplot "+t;if(!n.serialtimekey)throw".serialtimekey missing from survivalplot "+t;if(!n.iscensoredkey)throw".iscensoredkey missing from survivalplot "+t;if(!n.timelabel)throw".timelabel missing from survivalplot "+t;n.key=t,e.init.plottypes.push({key:t,name:n.name,timelabel:n.timelabel})}if(e.samplegroupattrlst){e.init.samplegroupings=[];for(const n of e.samplegroupattrlst){if(!n.key)throw".key missing from an attr of samplegroupattrlst for survival";const r=t.cohort.sampleAttribute.attributes[n.key];if(!r)throw'unknown attribute key "'+n.key+'" from survival samplegroupattrlst';const s=new Map;for(const r in t.cohort.annotation){const o=t.cohort.annotation[r],i=o[n.key];if(null==i)continue;let a=!1;for(const t in e.plots)if(null!=o[e.plots[t].serialtimekey]){a=!0;break}a&&(s.has(i)?s.set(i,s.get(i)+1):s.set(i,1))}if(0==s.size)throw'no value found for "'+n.key+'" from survival samplegroupattrlst';const o=[];for(const[t,e]of s)o.push({value:t,count:e});e.init.samplegroupings.push({key:n.key,label:r.label,values:o})}}}}if(t.mutationAttribute){if(!t.mutationAttribute.attributes)throw"attributes{} missing from mutationAttribute";for(const e in t.mutationAttribute.attributes){const n=t.mutationAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from mutationAttribute.attributes";if(!n.appendto_link&&n.values)for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from mutationAttribute.attributes"}}}if(t.alleleAttribute){if(!t.alleleAttribute.attributes)throw"attributes{} missing from alleleAttribute";for(const e in t.alleleAttribute.attributes){const n=t.alleleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from alleleAttribute.attributes";if(!n.isnumeric){if(!n.values)throw".values{} missing for non-numeric key "+e+" from alleleAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from alleleAttribute.attributes"}}}}if(t.locusAttribute){if(!t.locusAttribute.attributes)throw"attributes{} missing from locusAttribute";for(const e in t.locusAttribute.attributes){const n=t.locusAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from locusAttribute.attributes";if(!n.isnumeric&&!n.appendto_link){if(!n.values)throw".values{} missing for non-numeric key "+e+" from locusAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from locusAttribute.attributes"}}}}if(t.queries)for(const r in t.queries){if(n.remove_queries&&-1!=n.remove_queries.indexOf(r)){delete t.queries[r];continue}const s=t.queries[r];if(n.hide_queries&&-1!=n.hide_queries.indexOf(r)&&(s.hideforthemoment=1),s.istrack){if(!s.type)throw".type missing for track query "+r;if(s.viewrangeupperlimit&&!Number.isInteger(s.viewrangeupperlimit))throw".viewrangeupperlimit should be integer for track query "+r;if(s.type==P.tkt.mdsjunction){const n=go(s,t,e);if(n)throw r+" (mdsjunction) error: "+n}else if(s.type==P.tkt.mdscnv){const n=vo(s,t,e);if(n)throw r+" (mdscnv) error: "+n}else if(s.type==P.tkt.mdssvcnv){const n=wo(s,t,e);if(n)throw r+" (svcnv) error: "+n}else{if(s.type!=P.tkt.mdsvcf)throw"unknown track type for a query: "+s.type+" "+r;{const n=await xo(s,t,e);if(n)throw r+" (vcf) error: "+n}}mo(s,t)}else{if(!s.isgenenumeric)throw"unknown type of query from "+r;{const n=_o(s,t,e);if(n)throw r+" (genenumeric) error: "+n}}}if(t.track&&await Cr(t,e),t.annotationsampleset2matrix){if(!t.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!t.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!t.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!t.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!t.annotationsampleset2matrix.groups)throw".groups{} missing in annotationsampleset2matrix";if("object"!=typeof t.annotationsampleset2matrix.groups)throw"ds.annotationsampleset2matrix.groups{} not an object";for(const e in t.annotationsampleset2matrix.groups){const n=t.annotationsampleset2matrix.groups[e];if(!n.groups||!Array.isArray(n.groups)||0==n.groups.length)throw".groups[] must be nonempty array in "+e;for(const r of n.groups){if(!r.name)throw".name missing from one of .groups[] in "+e;const n=r.matrixconfig;if(!n)throw".matrixconfig missing from one of .groups[] of "+e;if(!n.features)throw".features[] missing from group "+e;if(!Array.isArray(n.features))throw".features[] should be array from group "+e;if(0==n.features.length)throw".features[] zero length from group "+e;for(const r of n.features){if(t.annotationsampleset2matrix.commonfeatureattributes)for(const e in t.annotationsampleset2matrix.commonfeatureattributes)null==r[e]&&(r[e]=t.annotationsampleset2matrix.commonfeatureattributes[e]);if(!r.ismutation)return"unknown feature type from group "+e;if(!r.position)throw"position missing from feature "+JSON.stringify(r)+" from group "+e;if(!r.querykeylst)throw".querykeylst[] missing from ismutation feature from group "+e;if(!Array.isArray(r.querykeylst))throw".querykeylst[] not an array from ismutation feature from group "+e;if(0==r.querykeylst.length)throw".querykeylst[] zero length from ismutation feature from group "+e;for(const n of r.querykeylst)if(!t.queries[n])throw'unknown query key "'+n+'" from ismutation feature of group '+e}if(!n.limitsamplebyeitherannotation)throw".limitsamplebyeitherannotation[] missing from group "+e;if(!Array.isArray(n.limitsamplebyeitherannotation))throw".limitsamplebyeitherannotation[] should be array from group "+e;if(0==n.limitsamplebyeitherannotation.length)throw".limitsamplebyeitherannotation[] zero length from group "+e;for(const t of n.limitsamplebyeitherannotation){if(!t.key)throw"key missing from one of limitsamplebyeitherannotation from group "+e;if(!t.value)throw"value missing from one of limitsamplebyeitherannotation from group "+e}}}delete t.annotationsampleset2matrix.commonfeatureattributes}}function mo(t,e){if(t.groupsamplebyattr){t.groupsamplebyattr.key2group=new Map;for(const n in e.cohort.annotation)Zs(n,[],t.groupsamplebyattr.key2group,[],e,t)}}function go(t,e,n){if(t.readcountCutoff&&(!Number.isInteger(t.readcountCutoff)||t.readcountCutoff<1))return"readcountCutoff must be positive integer";let r;if(t.file){const[e,n]=io(t.file);if(e)return"tabix file error: "+e;t.file=n,r=n}else{if(!t.url)return"no file or url given for mdsjunction "+t.name;r=t.url}const s={encoding:"utf8"};const o=N().execSync(vs+" -H "+r,s).trim();if(o){const n=o.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");if(r[5]){t.samples=r.slice(5),t.attributeSummary=yo(t.samples,e),t.hierarchySummary=bo(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}}{const e=N().execSync(vs+" -l "+r,s).trim();if(!e)return"no chromosomes found";t.nochr=P.contigNameNoChr(n,e.split("\n"))}if(console.log("(mdsjunction) "+t.name+": "+(t.samples?t.samples.length:0)+" samples, "+(t.nochr?'no "chr"':'has "chr"')),!t.infoFilter)return".infoFilter{} missing";if(!t.infoFilter.lst)return".lst[] missing from .infoFilter";for(const e of t.infoFilter.lst){if(!e.key)return".key missing from one of infoFilter";if(!e.label)return".label missing from one of infoFilter";if(!e.categories)return".categories missing from one of infoFilter";for(const t in e.categories){if(!e.categories[t].label)return".label missing from one category of "+e.label;if(!e.categories[t].color)return".color missing from on category of "+e.label}if(e.hiddenCategories){for(const t in e.hiddenCategories)if(!e.categories[t])return"invalid hidden key "+t+" of "+e.label}else e.hiddenCategories={}}if(!t.singlejunctionsummary)return".singlejunctionsummary missing but is currently required from "+t.name;if(t.singlejunctionsummary.readcountboxplotpercohort){if(!t.singlejunctionsummary.readcountboxplotpercohort.groups)return".groups[] missing from query.singlejunctionsummary.readcountboxplotpercohort for "+t.name;for(const e of t.singlejunctionsummary.readcountboxplotpercohort.groups){if(!e.key)return".key missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups";if(!e.label)return".label missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups"}}}function yo(t,e){if(!(e.cohort&&e.cohort.annotation&&e.cohort.attributes&&t))return;const n={};for(const r of e.cohort.attributes.lst){const s={};for(const t in r.values)s[t]=0;for(const n of t){const t=e.cohort.annotation[n];if(!t)continue;const o=t[r.key];null!=o&&(o in s&&s[o]++)}n[r.key]=s}return n}function bo(t,e){if(!e.cohort||!e.cohort.annotation||!e.cohort.hierarchies||0==t.length)return;const n=[];for(const r of t){const t=e.cohort.annotation[r];t&&n.push(t)}const r={};for(const t of e.cohort.hierarchies.lst){const e=(0,A.N)(n,t.levels),s=(0,V.Z)()(e);s.sum((t=>t.value));const o={};s.eachBefore((t=>{o[t.id]=t.value})),r[t.name]=o}return r}function vo(t,e,n){let r;if(t.file){const[e,n]=io(t.file);if(e)return"tabix file error: "+e;r=n}else{if(!t.url)return"no file or url given for (mdscnv) "+t.name;r=t.url}const s={encoding:"utf8"};const o=N().execSync(vs+" -H "+r,s).trim();if(o){const n=o.split("\n");if(1!=n.length)return"mdscnv file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");t.samples=r.slice(5),t.attributeSummary=yo(t.samples,e),t.hierarchySummary=bo(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}{const e=N().execSync(vs+" -l 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authorization route, use '${s.authRoute}'`;if(!t.headers.authorization)throw"missing authorization header";const[o,i]=t.headers.authorization.split(" ");if("basic"!=o.toLowerCase())throw`unsupported authorization type='${o}', allowed: 'Basic'`;if(Buffer.from(i,"base64").toString()!=s.password)throw"invalid password";const a=await p(r,e,k,v,"",t,s);n=401;const l=await d(t,r,a,s,x,v);e.send({status:"ok",jwt:l,route:s.route})}catch(t){e.status(n),e.send({error:t})}})),t.post(e+"/dslogout",(async(t,e)=>{try{const n=t.query,s=f(t,q(n,t.path));if(!s)throw"missing session cookie";const o=k[n.dslabel]?.[s];if(!o)return void e.send({status:"ok"});delete k[n.dslabel][s];t.ip;await r.promises.appendFile(v,`${n.dslabel}\t${s}\t0\t\t${o.ip}\t${o.embedder}\t${o.route}\n`),e.send({status:"ok"})}catch(t){e.status(401),e.send({error:t})}})),t.post(e+"/jwt-status",(async(t,e)=>{let n=401;try{const r=t.query,s=q(r,t.path);if(!s)return void e.send({status:"ok"});if("/jwt-status"!=s.authRoute)throw 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a=i[s],c=f({query:Object.assign({},t.query,{dslabel:r}),headers:t.headers,cookies:t.cookies},a),u=k[r]?.[c],d=u?.time||0;e.push({dslabel:r,route:o,type:a.type||"basic",insession:("basic"!=a.type||!t.path.startsWith("/genomes"))&&(("jwt"!=a.type||c)&&Date.now()-d<x)})}}}return e},y.getForbiddenRoutesForDsEmbedder=function(t,e){const n=[],r=_[t]||_["*"];if(!r)return n;for(const t in r){const s=r[t][e]||r[t]["*"];"forbidden"==s?.type&&n.push(t)}return n},y.getRequiredCredForDsEmbedder=function(t,e){const n=[];for(const r in _)if((0,l.isMatch)(t,r))for(const t in _[r])for(const s in _[r][t]){if(!(0,l.isMatch)(e,s))continue;const o=_[r][t][s];n.push({route:t,type:o.type,headerKey:o.headerKey})}return n},y.userCanAccess=function(t,e){const n=q(t.query,t.path,u.samples);if(!n)return!0;if("basic"==n.type&&t.path.startsWith("/genomes"))return!1;const r=f(t,n),s=h(k,e.label,r,t,n),o=k[e.label]?.[r]||k[e.label]?.[s],i=o?.time||0;return Date.now()-i<x},y.getPayloadFromHeaderAuth=function(t,e){if(!t.headers?.authorization)return{};const n=q(t.query,e);if(!n)return{};const[r,s]=t.headers.authorization.split(" ");if("bearer"!=r.toLowerCase())throw`unsupported authorization type='${r}', allowed: 'Bearer'`;const o=Buffer.from(s,"base64").toString();return a().verify(o,n.secret)||{}}},getJwtPayload:m,canDisplaySampleIds:(t,e)=>!!e.cohort.termdb.displaySampleIds&&y.userCanAccess(t,e),getDsAuth:()=>[],getForbiddenRoutesForDsEmbedder:()=>[],userCanAccess:()=>!0,getRequiredCredForDsEmbedder:()=>{},getPayloadFromHeaderAuth:()=>({})}},7833:(t,e,n)=>{"use strict";n.r(e);var r=n(7147),s=n.n(r),o=n(1017),i=n.n(o),a=(n(3345),n(334)),l=n.n(a),c=n(8907),u=n(8064),f=n(5494),d=n(6733),h=n(5558),p=n(3602),m=n(6279);const g={snvindel:f,sv:m,fusion:m,svjson:n(8423),cnv:d,itd:p,deletion:h,truncation:n(8235)};function y(t,e,n,r,s,o){for(const i of e.yesSamples){if(o&&!o.includes(i))continue;n.has(i)||n.set(i,{sample:i});const e=n.get(i);r in e||(e[r]={key:r,values:[],label:r}),s?e[r].values.some((e=>e.dt==t&&e.origin==s))||e[r].values.push({dt:parseInt(t),class:"WT",_SAMPLEID_:i,origin:s}):e[r].values.some((e=>e.dt==t))||e[r].values.push({dt:parseInt(t),class:"WT",_SAMPLEID_:i})}for(const i of e.noSamples){if(o&&!o.includes(i))continue;n.has(i)||n.set(i,{sample:i});const e=n.get(i);r in e||(e[r]={key:r,values:[],label:r}),s?e[r].values.some((e=>e.dt==t&&e.origin==s))||e[r].values.push({dt:parseInt(t),class:"Blank",_SAMPLEID_:i,origin:s}):e[r].values.some((e=>e.dt==t))||e[r].values.push({dt:parseInt(t),class:"Blank",_SAMPLEID_:i})}}async function b(t,e){const n=t.cohort;try{if(n.mutationFlagSet)return n.mutationFlagSet;if(!n.mutationset)return;const r={},s=t.sampleName2Id;for(const[t,o]of n.mutationset.entries()){const n=await v(t,o,e);r[Math.random()]=n;for(const t in n.data)for(const e of n.data[t])e._SAMPLENAME_=e.sample.split(";")[0].trim(),e._SAMPLEID_=s.get(e._SAMPLENAME_)||e._SAMPLENAME_}return n.mutationFlagSet=r,r}catch(t){throw t}}async function v(t,e,n){const r=u.Dz(n);if(!r)throw"init_bulk_flag() failed";r.tpsetname=e.name?e.name:"set"+t;for(const t in e){if(!(t in g))throw`unknown mutationset: ${t}`;const n=e[t].startsWith("/")?e[t]:i().join(l().tpmasterdir,e[t]);try{const e=(await s().promises.readFile(n,"utf8")).trim().split(/\r?\n/);if(g[t].parseheader(e[0],r))throw`${t} header line error: herr`;for(let n=1;n<e.length;n++)g[t].parseline(n,e[n],r)}catch(t){throw t}}return r}exports.mayGetGeneVariantData=async function(t,e){const n=this,r=t.term.name,s=await b(n,e.genome),o=new Map;if(!s)return o;let i;e?.filter?.lst.length>0&&(i=[...new Set((await(0,c.cf)(e.filter,n)).map((t=>t.id)))]);for(const t in s){const e=s[t];if(r in e.data){for(const t of e.data[r]){const e=t._SAMPLEID_;if(i&&!i.includes(e))continue;o.has(e)||o.set(e,{sample:e});const n=o.get(e);r in n||(n[r]={key:r,values:[],label:r}),n[r].values.push(t)}if(n.assayAvailability?.byDt)for(const t in n.assayAvailability.byDt){const e=n.assayAvailability.byDt[t];if(e.byOrigin)for(const n in e.byOrigin){y(t,e.byOrigin[n],o,r,n,i)}else y(t,e,o,r,!1,i)}}}return o},exports.getTermTypes=async function(t){const e=this;try{const n="string"==typeof t.ids?JSON.parse(t.ids):t.ids,r=n.map((()=>"?")).join(","),s=`SELECT id, name, type, jsondata, parent_id FROM terms WHERE id IN (${r}) OR name IN (${r})`,o=e.cohort.db.connection.prepare(s).all([...n,...n]),i={};for(const t of o)t.jsondata&&Object.assign(t,JSON.parse(t.jsondata)),i[t.id]=t;const a=n.filter((t=>!i[t])),l=await b(e,t.genome);if(l)for(const t in l){const e=l[t];if(e.data)for(const t of a)t in e.data&&!(t in i)&&(i[t]={name:t,type:"geneVariant"})}return i}catch(t){return t.stack&&console.log(t.stack),{error:t.message||t}}},exports.mayGetMatchingGeneNames=async function(t,e,n,r=25){const s=await b(this,n.genome);if(s)for(const n in s){const o=s[n];for(const n in o.data){if(n.length>r)continue;if(!o.data[n]?.length)continue;const s={name:n,type:"geneVariant",isleaf:!0};n===e?t.equals.push(s):n.startsWith(e)?t.startsWith.push(s):n.includes(" "+e)?t.startsWord.push(s):n.includes(e)?t.includes.push(s):"TP53"==n&&0}}},exports.get_flagset=b},4065:(t,e,n)=>{"use strict";function r(t,e){if(t.genomicNameRegexp.test(e.input))throw"invalid character in gene name";if(e.deep){const n={};let r;{const n=t.genedb.getnamebynameorisoform.get(e.input,e.input);n&&(r=n.name)}if(!r&&t.genedb.getNameByAlias){const n=t.genedb.getNameByAlias.get(e.input);n&&(r=n.name)}if(!r&&t.genedb.get_gene2canonicalisoform&&e.input.toUpperCase().startsWith("ENSG")){const s=t.genedb.get_gene2canonicalisoform.get(e.input);if(s&&s.isoform){const e=s.isoform;n.found_isoform=e;const o=t.genedb.getnamebynameorisoform.get(e,e);if(!o)throw"cannot map enst isoform to symbol";r=o.name}}r||(r=e.input);const s=t.genedb.getjsonbyname.all(r);return n.gmlst=s.map((t=>{const e=JSON.parse(t.genemodel);return t.isdefault&&(e.isdefault=!0),e})),n}const n=e.input.toUpperCase(),r=(n.substr(0,2),t.genedb.getnameslike.all(n+"%"));if(r.length)return r.sort(),{hits:r.map((t=>t.name))};if(t.genedb.getNameByAlias){const e=t.genedb.getNameByAlias.all(n);if(e.length)return{hits:e.map((t=>t.name))}}{const n=t.genedb.getnamebynameorisoform.get(e.input,e.input);if(n)return{hits:[n.name]}}return{hits:[]}}n.d(e,{S:()=>r})},2062:(t,e,n)=>{"use strict";n.d(e,{W:()=>a,A:()=>l});var r=n(334),s=n.n(r),o=n(7147),i=n.n(o);async function a(t){l.deps||async function(){const t=`${process.cwd()}/package.json`;try{if(!i().existsSync(t))return;{const e=i().readFileSync(t,{encoding:"utf8"}),n=JSON.parse(e),r=n?.dependencies["@sjcrh/proteinpaint-server"];r&&(l.deps["@sjcrh/proteinpaint-server"].entry=r);const s=n?.dependencies["@sjcrh/proteinpaint-client"];s&&(l.deps.entry["@sjcrh/proteinpaint-client"]||(l.deps["@sjcrh/proteinpaint-client"]={}),l.deps["@sjcrh/proteinpaint-client"]=s)}}catch(t){console.log(t)}}();const e={status:"ok",genomes:{},versionInfo:l};for(const n in t){const r=t[n],s={};if(r.genedb&&(s.genedb={buildDate:r.genedb.get_buildDate?.get().date||"unknown",tables:r.genedb.tableSize}),r.termdbs){s.termdbs={};for(const t in r.termdbs){const e=r.termdbs[t];s.termdbs[t]={buildDate:e.cohort.termdb.q.get_buildDate?.get().date||"unknown"}}}Object.keys(s).length&&e.genomes&&(e.genomes[n]=s)}return e}const l={pkgver:"2.42.1-0",codedate:function(){const t=i().existsSync(s().binpath+"/server.js")&&i().statSync(s().binpath+"/server.js").mtime||new Date(0),e=i().existsSync("public/bin/proteinpaint.js")&&i().statSync("public/bin/proteinpaint.js").mtime||new Date(0);return(t>e?t:e).toDateString()}(),launchdate:new Date(Date.now()).toString().split(" ").slice(0,5).join(" "),deps:{}},c=`${s().binpath}/package.json`;if(i().existsSync(c)){const t=JSON.parse(i().readFileSync(c,{encoding:"utf8"}));l.deps["@sjcrh/proteinpaint-server"]={installed:t.version}}const u=c.replace("server","client");if(i().existsSync(u)){const t=JSON.parse(i().readFileSync(u,{encoding:"utf8"}));l.deps["@sjcrh/proteinpaint-client"]={installed:t.version}}},9157:(t,e,n)=>{"use strict";n.r(e),n.d(e,{default:()=>c});var r=n(7147),s=n.n(r),o=(n(1017),n(334)),i=n.n(o),a=n(2081),l=n(2781);async function c(t,e,n=[]){try{await s().promises.stat(t)}catch(e){throw`${t} does not exist`}const r=[],o=[];return new Promise(((s,c)=>{const u=(0,a.spawn)(i().Rscript,[t,...n]);if(e&&e.length>0)try{const t=e.join("\n")+"\n";l.Readable.from(t).pipe(u.stdin)}catch(t){u.kill();let e=t;o.length>0&&(e+=`\nR stderr: ${o.join("").trim()}`),c(e)}u.stdout.on("data",(t=>r.push(t))),u.stderr.on("data",(t=>o.push(t))),u.on("error",(t=>c(t))),u.on("close",(t=>{if(0!==t){let e=`R process exited with non-zero status code=${t}`;r.length>0&&(e+=`\nR stdout: ${r.join("").trim()}`),o.length>0&&(e+=`\nR stderr: ${o.join("").trim()}`),c(e)}if(o.length>0){const t=o.join("").trim();c(`R process emitted standard error\nR stderr: ${t}`)}const e=r.join("").trim().split("\n");s(e)}))}))}},901:(t,e,n)=>{"use strict";n.d(e,{T:()=>s,w:()=>o});var r=n(8907);async function s(t,e,n){if(!e)return;const s=function(t,e){{const e=t.filter||t.filterObj;if(e){if(!Array.isArray(e.lst))throw"filterObj.lst is not array";return 0==e.lst.length?null:e}}if(t.tid2value){if("object"!=typeof t.tid2value)throw"q.tid2value{} not object";return o(t.tid2value,e)}}(t,n);if(!s)return;const i=[...new Set((await(0,r.cf)(s,n)).map((t=>t.id)))];let a;a=Number.isInteger(e[0])?new Set(e):new Set(e.map((t=>t.name)));const l=new Set;for(const t of i)a.has(t)&&l.add(t);return l}function o(t,e){const n={type:"tvslst",in:!0,join:"and",lst:[]};for(const r in t){const s=e.cohort.termdb.q.termjsonByOneid(r);if(!s)continue;const o=t[r];n.lst.push({type:"tvs",tvs:{term:s,values:[{key:o}]}})}return n}},1169:(t,e,n)=>{"use strict";n.d(e,{Ak:()=>m,Z5:()=>v,sV:()=>R,eG:()=>b,r8:()=>D,z7:()=>P,ws:()=>O,nD:()=>C,wm:()=>I,IK:()=>k,CN:()=>w,xq:()=>y,vK:()=>g});var r=n(2273),s=n(4048),o=n(6452),i=n.n(o),a=n(1017),l=n.n(a),c=n(4973);function u(t){const e={op:t.in?"and":"not",content:[]};if(!Array.isArray(t.lst))throw"filter.lst[] not array";for(const n of t.lst){if("tvs"!=n.type)throw'filter.lst[] item.type!="tvs"';if(!n.tvs)throw"item.tvs missing";if(!n.tvs.term)throw"item.tvs.term missing";if(n.tvs.values){const t={op:n.tvs.isnot?"!=":"in",content:{field:f(n.tvs.term.id),value:n.tvs.values.map((t=>t.key))}};e.content.push(t)}else{if(!n.tvs.ranges)throw"unknown tvs structure when converting to gdc filter";for(const t of n.tvs.ranges)t.startunbounded?e.content.push({op:t.stopinclusive?n.tvs.isnot?">":"<=":n.tvs.isnot?">=":"<",content:{field:f(n.tvs.term.id),value:t.stop}}):t.stopunbounded?e.content.push({op:t.startinclusive?n.tvs.isnot?"<":">=":n.tvs.isnot?"<=":">",content:{field:f(n.tvs.term.id),value:t.start}}):n.tvs.isnot?e.content.push({op:"or",content:[{op:"and",content:[{op:t.startinclusive?"<":"<=",content:{field:f(n.tvs.term.id),value:t.start}}]},{op:"and",content:[{op:t.stopinclusive?">":">=",content:{field:f(n.tvs.term.id),value:t.stop}}]}]}):e.content.push({op:"and",content:[{op:t.startinclusive?">=":">",content:{field:f(n.tvs.term.id),value:t.start}},{op:t.stopinclusive?"<=":"<",content:{field:f(n.tvs.term.id),value:t.stop}}]})}}return e}function f(t){const e=t.split(".");return"case"==e[0]&&(e[0]="cases"),e.join(".")}n(3345);var d=n(334),h=n.n(d);function p(...t){h().debugmode&&console.log(t.join(" "))}function m(t,e){t.convertSampleId.get=t=>{const n={};for(const r of t)n[r]=e.__gdc.map2caseid.get(r)||r;return n}}async function g(t,e){const n=["consequence.transcript.is_canonical","consequence.transcript.transcript_id"];t.get=async t=>{if(!t.ssm_id)throw".ssm_id missing";const{host:r,headers:s}=e(t),o=await i()(r.rest+"/ssms/"+t.ssm_id+"?fields="+n.join(","),{method:"GET",headers:s});let a;try{a=JSON.parse(o.body)}catch(t){throw"invalid json in response"}if(!a.data||!a.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(a.data.consequence))throw".data.consequence not array";const l=a.data.consequence.find((t=>t.transcript.is_canonical));return l?l.transcript.transcript_id:a.data.consequence[0].transcript.transcript_id}}function y(t){t.queries.snvindel.byrange.get=async e=>await t.queries.snvindel.byisoform.get(e)}function b(t,e){t.queries.geneExpression.get=async n=>{if(!Array.isArray(n.genes))throw"q.genes[] not array";const r=new Map,s=new Date,o=await v(n,t);if(0==o.length)return{gene2sample2value:r,byTermId:{}};const a=new Date;p(o.length,"cases with exp data:",a-s,"ms");const[l,c]=await async function(t,e,n,r,s){const o=[],a=new Map;for(const n of t){const t=n.gene||n.name;if("string"!=typeof t)continue;if(t.startsWith("ENSG")&&15==t.length){o.push(t),a.set(t,t);continue}const r=e.genedb.getAliasByName.all(t);if(Array.isArray(r))for(const e of r)if(e.alias.startsWith("ENSG")){o.push(e.alias),a.set(e.alias,t);break}if(o.length>100)break}try{const{host:t,headers:e}=r.getHostHeaders(s),l=await i().post(`${t.geneExp}/gene_expression/gene_selection`,{headers:e,body:JSON.stringify({case_ids:n,gene_ids:o,selection_size:o.length})}),c=JSON.parse(l.body);if(!Array.isArray(c.gene_selection))throw"re.gene_selection[] not array";const u=[];for(const t of c.gene_selection){if("string"!=typeof t.gene_id)throw".gene_id missing from one of re.gene_selection[]";u.push(t.gene_id)}return[u,a]}catch(t){throw t}}(n.genes,e,o,t,n);if(0==l.length)return{gene2sample2value:r,byTermId:{}};const u=new Date;p(l.length,"out of",n.genes.length,"genes selected for exp:",u-a,"ms");const f={};for(const t of l){const e=c.get(t);f[e]={gencodeId:t},r.set(e,new Map)}const d=await async function(t,e,n,r,s,o){const{host:a,headers:l}=o.getHostHeaders(t),c=await i().post(`${a.geneExp}/gene_expression/values`,{headers:l,body:JSON.stringify({case_ids:n,gene_ids:e,format:"tsv",tsv_units:"uqfpkm"})});if("string"!=typeof c.body)throw"response.body is not tsv text";const u=c.body.trim().split("\n");if(u.length<=1)throw"less than 1 line from tsv response.body";const f=u[0].split("\t").slice(1);if(f.length!=n.length)throw"sample column length != case_ids.length";const d={};for(const t of f){const e=o.__gdc.caseid2submitter.get(t);if(!e)throw"case submitter id unknown for a uuid";d[t]={label:e}}for(let t=1;t<u.length;t++){const e=u[t].split("\t");if(e.length!=f.length+1)throw"number of fields in gene line does not equal header";const n=e[0];if(!n)throw"ensg l[0] missing from a line";const o=r.get(n);if(!o)throw"symbol missing for "+n;for(const[t,n]of f.entries()){const r=Number(e[t+1]);if(!Number.isFinite(r))throw"non-numeric exp value from gdc";s.get(o)[n]=r}}return d}(n,l,o,c,r,t);return p("gene-case matrix built:",new Date-u,"ms"),{gene2sample2value:r,byTermId:f,bySampleId:d}}}async function v(t,e){const n={op:"and",content:[]};t.filter0&&n.content.push(t.filter0),t.filterObj&&n.content.push(u(t.filterObj)),t.filter&&n.content.push(u(t.filter));const r={size:1e4,fields:"case_id"};n.content.length&&(r.case_filters=n);try{const{host:n,headers:s}=e.getHostHeaders(t),o=await i().post(l().join(n.rest,"cases"),{headers:s,body:JSON.stringify(r)}),a=JSON.parse(o.body);if(!Array.isArray(a.data.hits))throw"re.data.hits[] not array";const c=[];for(const t of a.data.hits)if(t.id&&e.__gdc.casesWithExpData.has(t.id)&&(c.push(t.id),1e3==c.length))break;return c}catch(t){throw t.stack&&console.log(t.stack),t}}function w(t){t.queries.snvindel.byisoform.get=async e=>{const n=_(e,t),s=await async function(t,e){const n=L,r=z,{host:s,headers:o}=e.getHostHeaders(t),a=i().post(l().join(s.rest,n.endpoint),{headers:o,body:JSON.stringify(Object.assign({size:n.size,fields:n.fields.join(",")},n.filters(t)))}),c=i().post(l().join(s.rest,r.endpoint),{headers:o,body:JSON.stringify(Object.assign({size:r.size,fields:r.fields.join(",")},r.filters(t,e)))}),[u,f]=await Promise.all([a,c]);let d,h;try{d=JSON.parse(u.body),h=JSON.parse(f.body)}catch(t){throw"invalid JSON returned by GDC"}if(!d.data||!d.data.hits)throw"query1 did not return .data.hits";if(!h.data||!h.data.hits)throw"query2 did not return .data.hits[]";if(!Array.isArray(d.data.hits)||!Array.isArray(h.data.hits))throw"re.data.hits[] is not array";const p=new Map;for(const e of d.data.hits){if(!e.ssm_id)throw"ssm_id missing from a ssms hit";if(!e.consequence)throw".consequence[] missing from a ssm";if(!Number.isInteger(e.start_position))throw"hit.start_position is not integer";let n;e.csqcount=e.consequence.length,n=t.isoform?e.consequence.find((e=>e.transcript.transcript_id==t.isoform)):e.consequence.find((t=>t.transcript.is_canonical)),e.consequence=n||e.consequence[0],e.cases=[],p.set(e.ssm_id,e)}for(const t of h.data.hits){if(!t.ssm)throw".ssm{} missing from a case";if(!t.ssm.ssm_id)throw".ssm.ssm_id missing from a case";const e=p.get(t.ssm.ssm_id);if(!e)throw"ssm_id not found in ssms query";if(!t.case)throw".case{} missing from a case";e.cases.push(t.case)}return[...p.values()]}(e,t),o=[];for(const t of s){const n={ssm_id:t.ssm_id,dt:r.dtsnvindel,chr:t.chromosome,pos:t.start_position-1,ref:t.reference_allele,alt:t.tumor_allele,isoform:e.isoform,csqcount:t.csqcount};if(x(n,t.consequence),!e.hiddenmclass||!e.hiddenmclass.has(n.class)){n.samples=[];for(const r of t.cases){const t={};if(e.gdcUseCaseuuid){if(t.sample_id=r.case_id,!t.sample_id)throw"gdcUseCaseuuid=true but c.case_id undefined"}else if(t.sample_id=r.observation?.[0]?.sample?.tumor_sample_uuid,!t.sample_id)throw"gdcUseCaseuuid=false but c.observation?.[0]?.sample?.tumor_sample_uuid undefined";n.samples.push(t)}o.push(n)}}if(n){e.isoform=n;for(const t of o)t.isoform=n}return o}}function _(t,e){if(!t.isoform)return;let n;if("N"==t.isoform[0]&&e.refseq2ensembl_query){const r=e.refseq2ensembl_query.get(t.isoform);r&&(n=t.isoform,t.isoform=r.ensembl)}return n}function x(t,e){if(e&&e.transcript.consequence_type){const[n,s,o]=r.vepinfo(e.transcript.consequence_type);t.class=s,t.mname=e.transcript.aa_change}t.mname||(t.mname=t.ref+">"+t.alt),t.class||(r.basecolor[t.ref]&&r.basecolor[t.alt]?t.class=r.mclasssnv:"-"==t.ref?t.class=r.mclassinsertion:"-"==t.alt?t.class=r.mclassdeletion:t.class=r.mclassmnv)}function k(t){const e=["cnv.cnv_change","cnv.gene_level_cn","cnv.consequence.gene.symbol","case.submitter_id","case.case_id"];function n(t){const n=e.slice();if(t.twLst)for(const e of t.twLst){let t=e.term.id;t.startsWith("case.")&&(t="occurrence."+t),n.push(t)}return n.join(",")}function s(t){if(!t.gene&&"string"!=typeof t.gene)throw"p.gene does not provide non-empty string";const e={filters:{op:"and",content:[]},case_filters:{op:"and",content:[]}};return t.gene&&e.filters.content.push({op:"=",content:{field:"cnv.consequence.gene.symbol",value:t.gene.split(",")}}),t.filter0&&e.case_filters.content.push(t.filter0),t.filterObj&&e.case_filters.content.push(u("string"==typeof t.filterObj?JSON.parse(t.filterObj):t.filterObj)),e}t.queries.geneCnv.bygene.get=async e=>{const{host:o,headers:a}=t.getHostHeaders(e),c=await i().post(l().join(o.rest,"cnv_occurrences"),{headers:a,body:JSON.stringify(Object.assign({size:1e5,fields:n(e)},s(e)))}),u=JSON.parse(c.body);if(!Array.isArray(u?.data?.hits))throw"geneCnv response body is not {data:hits[]}";const f={ssm_id:"geneCnvGain",dt:r.dtcnv,class:r.mclasscnvgain,samples:[]},d={ssm_id:"geneCnvLoss",dt:r.dtcnv,class:r.mclasscnvloss,samples:[]};for(const t of u.data.hits){if("object"!=typeof t.cnv)throw"hit.cnv{} not obj";if("object"!=typeof t.case)throw"hit.case{} not obj";if(!t.cnv.gene_level_cn)throw"hit.cnv.gene_level_cn is not true";let n;if("Gain"==t.cnv.cnv_change)n=f;else{if("Loss"!=t.cnv.cnv_change)throw"hit.cnv.cnv_change is not Gain/Loss";n=d}const r={sample_id:t.case.case_id};if(e.twLst)for(const n of e.twLst)S(r,t.case,n);n.samples.push(r)}const h=[];return f.samples.length&&h.push(f),d.samples.length&&h.push(d),h}}function N(t,e){if(!e)return;const n=e.split(",");for(const e of n){const n=e.split("--");if(2==n.length)return t.geneA=n[0].split("(")[0],void(t.geneB=n[1].split("(")[0])}}function S(t,e,n){const r=n.term.id.split(".");if(function e(s,o){const i=r[o];if(o==r.length-1)return void(t[n.term.id]?t[n.term.id].add(s[i]):t[n.term.id]=s[i]);const a=s[i];if(null==a)return;if(Array.isArray(a)){t[n.term.id]=new Set;for(const t of a)e(t,o+1);return}e(a,o+1)}(e,1),t[n.term.id]instanceof Set&&(t[n.term.id]=[...t[n.term.id]][0]),n.term.id in t&&"categorical"==n.term.type){const e=function(t,e){if("custom-groupset"==e.q?.type&&Array.isArray(e.q?.groupsetting?.customset?.groups))for(const n of e.q.groupsetting.customset.groups){if(!Array.isArray(n.values))throw"group.values[] not array from tw.q.groupsetting.customset.groups";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}if("predefined-groupset"==e.q?.type&&Number.isInteger(e.q.groupsetting?.predefined_groupset_idx)&&e.term.groupsetting?.lst[e.q.groupsetting.predefined_groupset_idx])for(const n of e.term.groupsetting.lst[e.q.groupsetting.predefined_groupset_idx]){if(!Array.isArray(n.values))throw"group.values[] not array from tw.term.groupsetting.lst[]";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}}(t[n.term.id],n);e&&(t[n.term.id]=e)}}function A(t,e){const n={};for(const r of e)if(("integer"==r.term.type||"float"==r.term.type)&&r.q?.mode)if("discrete"==r.q.mode||"binary"==r.q.mode){const e={};for(const n of t){const t=n[r.term.id];Number.isFinite(t)&&("min"in e?(e.min=Math.min(t,e.min),e.max=Math.max(t,e.max)):(e.min=t,e.max=t))}const o=(0,s.gp)(r.q,(t=>e),r.term.valueConversion);for(const t of o)t.name=t.label;n[r.term.id]={bins:o};for(const e of t){const t=e[r.term.id];Number.isFinite(t)&&(e[r.term.id]=M(o,t))}}else if("continuous"!=r.q.mode)throw"mayApplyBinning: unknown numeric q.mode";return n}function M(t,e){for(const n of t)if(n.startunbounded){if(e<n.stop)return n.label;if(n.stopinclusive&&e==n.stop)return n.label}else if(n.stopunbounded){if(e>n.start)return n.label;if(n.startinclusive&&e==n.start)return n.label}else if((e>n.start||e===n.start&&n.startinclusive)&&(e<n.stop||e===n.stop&&n.stopinclusive))return n.label}function T(t){for(const e of t)if(null==e.id||""==e.id){if(!e?.term?.id)throw"tw.id and tw.term are both missing";e.id=e.term.id}else e.term||(e.term={id:e.id})}async function C(t,e,n,r){if(t.isHierCluster)return await async function(t,e,n){const r={op:"and",content:[]};t.filter0&&r.content.push(t.filter0);t.filterObj&&r.content.push(u(t.filterObj));const s=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&s.push({term:e,q:t.q})}const o=["case_id"],a=new Map;for(const t of s){const e=t.term.id.replace(/^case\./,"");o.push(e),a.set(e,t.term.id)}const{host:c,headers:f}=n.getHostHeaders(t),d=await i().post(l().join(c.rest,"cases"),{headers:f,body:JSON.stringify({size:n.__gdc.casesWithExpData.size,fields:o.join(","),case_filters:r.content.length?r:void 0})}),h=JSON.parse(d.body);if(!Array.isArray(h?.data?.hits))throw"re.data.hits[] not array";const p=[];for(const t of h.data.hits){if("string"!=typeof t.case_id)throw"h.case_id missing";if(!n.__gdc.casesWithExpData.has(t.case_id))continue;const e={sample_id:t.case_id};for(const n of s)S(e,t,n);p.push(e)}const m=A(p,s);return{byTermId:m,samples:p}}(t,e,n);if(T(e),r){if(!Array.isArray(r))throw"geneTwLst not array";t.isoforms=[];for(const e of r){if(!e?.term?.name)throw"gene tw missing .term.name";if(e.term.isoform)t.isoforms.push(e.term.isoform);else{if("object"!=typeof t.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(!t.genome?.genedb?.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const n=t.genome.genedb.get_gene2canonicalisoform.get(e.term.name);if(!n?.isoform)continue;t.isoforms.push(n.isoform)}}}e.some((t=>"case.observation.sample.tumor_sample_uuid"==t.id))||e.push({term:{id:"case.observation.sample.tumor_sample_uuid"}}),e.some((t=>"case.case_id"==t.id))||e.push({term:{id:"case.case_id"}}),"samples"==t.get&&(t.ssm_id_lst||t.isoform)&&(e.some((t=>"ssm.ssm_id"==t.id))||e.push({term:{id:"ssm.ssm_id"}}),e.some((t=>"case.observation.read_depth.t_alt_count"==t.id))||e.push({term:{id:"case.observation.read_depth.t_alt_count"}}),e.some((t=>"case.observation.read_depth.t_depth"==t.id))||e.push({term:{id:"case.observation.read_depth.t_depth"}}),e.some((t=>"case.observation.read_depth.n_depth"==t.id))||e.push({term:{id:"case.observation.read_depth.n_depth"}}));const s=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&s.push({term:e,q:t.q})}const o=e.map((t=>t.term.id));t.hiddenmclass&&(o.push("ssm.consequence.transcript.consequence_type"),o.push("ssm.consequence.transcript.transcript_id"),o.push("ssm.consequence.transcript.is_canonical")),t.rglst&&(o.push("ssm.chromosome"),o.push("ssm.start_position"));const a={size:1e4,fields:o.join(",")};_(t,n),Object.assign(a,z.filters(t,n));const{host:f,headers:d}=n.getHostHeaders(t),h=await i().post(l().join(f.rest,z.endpoint),{headers:d,body:JSON.stringify(a)});let p;delete t.isoforms;try{p=JSON.parse(h.body)}catch(t){throw"invalid JSON from GDC for variant2samples query"}if(!p.data||!p.data.hits)throw"variant2samples data structure not data.hits[]";if(!Array.isArray(p.data.hits))throw"variant2samples re.data.hits is not array for query";const m=[];for(const e of p.data.hits){if(!e.case)throw"variant2samples .case{} missing from a hit";const r={};if(e.ssm&&(r.ssm_id=e.ssm.ssm_id),t.hiddenmclass){if(!Array.isArray(e.ssm?.consequence))continue;let n;n=t.isoform?e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform)):e.ssm.consequence.find((t=>t.transcript.is_canonical));const r={};if(x(r,n||e.ssm.consequence[0]),t.hiddenmclass.has(r.class))continue}if(t.gdcUseCaseuuid){if(r.sample_id=e.case.case_id,!r.sample_id)throw"querySamples_gdcapi: case.case_id missing"}else{const t=e.case?.observation?.[0]?.sample?.tumor_sample_uuid;if(!t)throw"querySamples_gdcapi: aliquot_id missing";r.sample_id=await n.__gdc.aliquot2submitter.get(t),r.sample_URLid=e.case.case_id+"?bioId="+t}for(const t of s)S(r,e.case,t);j(e.case,r),E(r,n),m.push(r)}const g=A(m,s);if(r){const t={gene:r.map((t=>t.term.name)).join(","),twLst:s},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)m.push(e)}const y=new Map;for(const t of m)(0,c.z9)([t],y,t.ssm_id);return{byTermId:g,samples:[...y.values()]}}function j(t,e){if(!t.observation)return;const n=t.observation[0];n&&n.read_depth&&(e.formatK2v={TumorAC:n.read_depth.t_depth-n.read_depth.t_alt_count+","+n.read_depth.t_alt_count,NormalDepth:n.read_depth.n_depth})}function E(t,e){const n=t["case.project.project_id"];n&&(t.caseIsOpenAccess=e.__gdc.gdcOpenProjects?.has(n))}async function O(t,e,n,r){T(t);const s=[];for(const e of t)e.term&&"categorical"==e.term.type&&s.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const o=function(t){const e=[];for(const n of t)if(n.id)if(n.type="categorical")e.push(n.path+" {buckets { doc_count, key }}");else{if("integer"!=n.type&&"float"!=n.type)throw"unknown term type";e.push(n.path+" {stats { count }}")}const n=`query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (case_filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\t${e.join("\n")}\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t}`;return n}(s),a=function(t,e){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};Z(t?.tid2value,n.filters.content,e),t&&t.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:t.ssm_id_lst.split(",")}});t.filter0&&n.filters.content.push(t.filter0);t.filterObj&&n.filters.content.push(u(t.filterObj));return n}(e,r),{host:l,headers:c}=r.getHostHeaders(e),f=await i().post(l.graphql,{headers:c,body:JSON.stringify({query:o,variables:a})});let d;try{d=JSON.parse(f.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+o+" and filter: "+filter}const h=["data","explore","cases","aggregations"];let p=d[h[0]];for(let t=1;t<h.length;t++)if(p=p[h[t]],!p)throw`.${h[t]} missing from data structure of termid2totalsize2 for query :${o} and filter: ${filter}`;for(const t of s){if("categorical"==t.type&&!Array.isArray(p[t.path].buckets))throw h.join(".")+" not array for query :"+o+" and filter: "+filter;if(("integer"==t.type||"float"==t.type)&&"object"!=typeof p[t.path].stats)throw h.join(".")+" not object for query :"+o+" and filter: "+filter}const m=new Map;for(const t of s)if("categorical"==t.type){const e=p[t.path].buckets,n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);m.set(t.id,n)}else if("integer"==t.type||"float"==t.type){const e=p[t.path].stats.count;m.set(t.id,{total:e})}return n?[m,n]:m}function I(t){const e=["consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change"];t.queries.snvindel.m2csq.get=async n=>{const{host:r,headers:s}=t.getHostHeaders(n),o=await i()(r.rest+"/ssms/"+n.ssm_id+"?fields="+e.join(","),{method:"GET",headers:s});let a;try{a=JSON.parse(o.body)}catch(t){throw"invalid json in response"}if(!a.data||!a.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(a.data.consequence))throw".data.consequence not array";return a.data.consequence.map((t=>t.transcript))}}function R(t,e){t.queries.singleSampleMutation.get=async e=>{if(e.sample.startsWith("___")){const t=e.sample.substring(3);if(!t)throw"expecting uuid after prefix but got blank";e.case_id=t}else t.__gdc.caseid2submitter.has(e.sample)?e.case_id=e.sample:(e.case_id=t.__gdc.map2caseid.get(e.sample),e.case_id||(e.case_id=await F(e.sample,t)));return await async function(t,e,n){const s={mlst:[],dt2total:[]};{const{host:n,headers:o}=e.getHostHeaders(t),a=await i().post(l().join(n.rest,L.endpoint),{headers:o,body:JSON.stringify({size:1e4,fields:L.fields.join(","),filters:L.filters(t).filters})}),c=JSON.parse(a.body);if(!Number.isInteger(c.data?.pagination?.total))throw"re.data.pagination.total not integer";if(!Array.isArray(c.data?.hits))throw"re.data.hits[] not array";c.data.hits.length<c.data.pagination.total&&s.dt2total.push({dt:1,total:c.data.pagination.total});for(const t of c.data.hits){let e=t.consequence.find((t=>1==t.transcript.is_canonical));e||(e=t.consequence[0]);const n=e.transcript.aa_change||e.transcript.consequence_type,[o,i,a]=r.vepinfo(e.transcript.consequence_type);s.mlst.push({dt:r.dtsnvindel,mname:n,class:i,gene:e.transcript.gene.symbol,chr:t.chromosome,pos:t.start_position,ref:t.reference_allele,alt:t.tumor_allele})}}{const n=await async function(t,e){const{host:n,headers:s}=e.getHostHeaders(t),o=await i().post(l().join(n.rest,"files"),{headers:s,body:JSON.stringify({size:1e4,fields:["cases.samples.sample_type","data_type","file_id","data_format","experimental_strategy","analysis.workflow_type"].join(","),filters:function(t){if(!t.case_id)throw".case_id missing";return{op:"and",content:[{op:"in",content:{field:"cases.case_id",value:[t.case_id]}},{op:"in",content:{field:"data_type",value:["Masked Copy Number Segment","Copy Number Segment","Transcript Fusion"]}}]}}(t)})}),a=JSON.parse(o.body);if(!Array.isArray(a.data.hits))throw"re.data.hits[] not array";let c,u,f;for(const t of a.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){const e=t.cases?.[0].samples?.[0]?.sample_type;if(!e)continue;if(e.includes("Normal"))continue;if("Masked Copy Number Segment"!=t.data_type)continue;c=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;u=t.file_id;continue}}}else{if("RNA-Seq"!=t.experimental_strategy)continue;if("Arriba"!=t.analysis?.workflow_type)continue;if("Transcript Fusion"!=t.data_type)continue;f=t.file_id}const d=[];if(u){const t=(await i()(l().join(n.rest,"data")+"/"+u,{method:"GET",headers:s})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(7!=n.length)continue;const s=Number(n[4]),o=Number(n[5]),i=Number(n[6]);if(Number.isNaN(s)||Number.isNaN(o)||Number.isNaN(i))continue;const a={dt:r.dtcnv,chr:n[1],start:Number(n[2]),stop:Number(n[3]),value:s};!a.chr||Number.isNaN(a.start)||Number.isNaN(a.stop)||(d.push(a),s>0&&0==i&&o>0&&d.push({dt:r.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(c){const t=(await i()(l().join(n.rest,"data")+"/"+c,{method:"GET",headers:s})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(6!=n.length)continue;if(!n[1])continue;const s={dt:r.dtcnv,chr:"chr"+n[1],start:Number(n[2]),stop:Number(n[3]),value:Number(n[5])};Number.isNaN(s.start)||Number.isNaN(s.stop)||Number.isNaN(s.value)||d.push(s)}}if(f)try{const t=(await i()(l().join(n.rest,"data")+"/"+f,{method:"GET",headers:s})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t"),s={dt:r.dtfusionrna,chrA:n[0],posA:Number(n[1]),chrB:n[3],posB:Number(n[4])};s.chrA&&s.chrB&&!Number.isNaN(s.posA)&&!Number.isNaN(s.posB)&&(N(s,n[6]),d.push(s))}}catch(t){}return d}(t,e);s.mlst.push(...n)}return s}(e,t)}}async function F(t,e){const{host:n,headers:r}=e.getHostHeaders(q),s=await i().post(`${n.rest}/cases`,{headers:r,body:JSON.stringify({size:1,fields:"case_id,submitter_id",filters:{op:"or",content:[{op:"=",content:{field:"samples.portions.analytes.aliquots.aliquot_id",value:[t]}},{op:"=",content:{field:"submitter_id",value:[t]}},{op:"=",content:{field:"samples.submitter_id",value:[t]}}]}})}),o=JSON.parse(s.body);for(const t of o.data.hits)if(t.case_id)return t.case_id;throw"cannot convert to case_id (uuid)"}function P(t,e){t.queries.singleCell.samples.get=async e=>{const n={op:"and",content:[]};e.filter0&&n.content.push(e.filter0);const r={filters:{op:"and",content:[{op:"=",content:{field:"data_format",value:"tsv"}},{op:"=",content:{field:"data_type",value:"Single Cell Analysis"}},{op:"=",content:{field:"experimental_strategy",value:"scRNA-Seq"}}]},case_filters:n,size:100,fields:["id","cases.submitter_id","cases.project.project_id","cases.samples.sample_type","cases.samples.submitter_id","cases.primary_site","cases.disease_type"].join(",")},{host:s,headers:o}=t.getHostHeaders(e),a=await i().post(l().join(s.rest,"files"),{headers:o,body:JSON.stringify(r)});let c;try{c=JSON.parse(a.body)}catch(t){throw"invalid JSON from "+api.endpoint}if(!Number.isInteger(c.data?.pagination?.total))throw"re.data.pagination.total is not int";if(!Array.isArray(c.data?.hits))throw"re.data.hits[] not array";const u=new Map;for(const t of c.data.hits){if(!t.id)throw"h.id (fileId) missing";const e=t.id,n=t.cases?.[0];if(!n)throw"h.cases[0] missing";const r=n.submitter_id;if(u.has(r)||u.set(r,{sample:r,primarySite:n.primary_site,diseaseType:n.disease_type,projectId:n.project?.project_id,files:[]}),!n.samples?.[0])throw"h.cases[0].samples[0] missing";u.get(r).files.push({fileId:e,sampleName:n.samples[0].submitter_id,sampleType:n.samples[0].sample_type})}return{samples:[...u.values()],fields:t.queries.singleCell.samples.fields,columnNames:t.queries.singleCell.samples.columnNames}}}function D(t,e){t.queries.singleCell.data.get=async e=>{const{host:n,headers:r}=t.getHostHeaders(e),s=(await i()(l().join(n.rest,"data",e.sample),{method:"GET",headers:r})).body.trim().split("\n"),o={name:"UMAP",cells:[],colorBy:"Cluster"},a={name:"TSNE",cells:[],colorBy:"Cluster"},c={name:"PCA",cells:[],colorBy:"Cluster"},u={id:"cluster",name:"Seurat cluster",type:"categorical",values:{}},f={[u.id]:{}};for(let t=1;t<s.length;t++){const e=s[t],n=e.split("\t"),r=n[0];if(!r)throw"cellId missing from a line: "+e;const i=n[3];if(!i)throw"seuratCluster missing from a line";u.values[i]={label:"Cluster "+i},f[u.id][r]=`Cluster ${i}`;const l=Number(n[4]),d=Number(n[5]),h=Number(n[9]),p=Number(n[10]),m=Number(n[14]),g=Number(n[15]);if(Number.isNaN(l))throw"umap1 is nan";if(Number.isNaN(d))throw"umap2 is nan";if(Number.isNaN(h))throw"tsne1 is nan";if(Number.isNaN(p))throw"tsne2 is nan";if(Number.isNaN(m))throw"pc1 is nan";if(Number.isNaN(g))throw"pc2 is nan";const y=`Cluster ${i}`;o.cells.push({cellId:r,x:l,y:d,category:y}),a.cells.push({cellId:r,x:h,y:p,category:y}),c.cells.push({cellId:r,x:m,y:g,category:y})}return{plots:[a,o,c],terms:[u],tid2cellvalue:f}}}const L={endpoint:"/ssms",size:1e5,fields:["ssm_id","chromosome","start_position","reference_allele","tumor_allele","consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change","consequence.transcript.gene.symbol","consequence.transcript.is_canonical"],filters:t=>{const e={filters:{op:"and",content:[]},case_filters:{op:"and",content:[]}};let n;if(t.rglst&&(n=t.rglst[0],$(n)),t.isoform){if("string"!=typeof t.isoform)throw".isoform value not string";e.filters.content.push({op:"=",content:{field:"consequence.transcript.transcript_id",value:[t.isoform]}}),n&&(e.filters.content.push({op:">=",content:{field:"start_position",value:n.start}}),e.filters.content.push({op:"<=",content:{field:"start_position",value:n.stop}}))}else if(n)e.filters.content.push({op:"=",content:{field:"chromosome",value:n.chr}}),e.filters.content.push({op:">=",content:{field:"start_position",value:n.start}}),e.filters.content.push({op:"<=",content:{field:"start_position",value:n.stop}});else{if(!t.case_id)throw".isoform, .rglst, and .case_id are all missing";if("string"!=typeof t.case_id)throw".case_id value not string";e.filters.content.push({op:"=",content:{field:"cases.case_id",value:[t.case_id]}})}if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";e.case_filters.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&e.case_filters.content.push(t.filter0),t.filterObj&&e.case_filters.content.push(u(t.filterObj)),e}};function $(t){if("object"!=typeof t)throw"p.rglst[0] not object";if("string"!=typeof t.chr||!t.chr||!Number.isInteger(t.start)||!Number.isInteger(t.stop))throw"p.rglst[0] not valid {chr,start,stop}"}const z={endpoint:"/ssm_occurrences",size:1e5,fields:["ssm.ssm_id","case.case_id","case.submitter_id","case.observation.sample.tumor_sample_uuid"],filters:(t,e)=>{const n={filters:{op:"and",content:[]},case_filters:{op:"and",content:[]}};let r=!1;if(t.ssm_id_lst){if("string"!=typeof t.ssm_id_lst)throw"ssm_id_lst not string";n.filters.content.push({op:"=",content:{field:"ssm.ssm_id",value:t.ssm_id_lst.split(",")}}),r=!0}else if(t.isoform)n.filters.content.push({op:"=",content:{field:"ssms.consequence.transcript.transcript_id",value:[t.isoform]}}),r=!0;else if(t.isoforms){if(!Array.isArray(t.isoforms))throw".isoforms[] not array";n.filters.content.push({op:"in",content:{field:"ssms.consequence.transcript.transcript_id",value:t.isoforms}}),r=!0}{let e;if(t.rglst&&(e=t.rglst[0],$(e)),r)e&&(n.filters.content.push({op:">=",content:{field:"ssms.start_position",value:e.start}}),n.filters.content.push({op:"<=",content:{field:"ssms.start_position",value:e.stop}}));else{if(!e)throw".ssm_id_lst, .isoform, .isoforms, .rglst[] are all missing";n.filters.content.push({op:"=",content:{field:"ssms.chromosome",value:e.chr}}),n.filters.content.push({op:">=",content:{field:"ssms.start_position",value:e.start}}),n.filters.content.push({op:"<=",content:{field:"ssms.start_position",value:e.stop}})}}if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";n.case_filters.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&n.case_filters.content.push(t.filter0),t.filterObj&&n.case_filters.content.push(u(t.filterObj)),Z(t.tid2value,n.case_filters.content,e),n}};function Z(t,e,n){if(t)for(const r in t){const s=n.cohort.termdb.q.termjsonByOneid(r);if(!s)continue;const o=r.replace(/^case\./,"cases.");if("categorical"==s.type)e.push({op:"in",content:{field:o,value:[t[r]]}});else if("integer"==s.type)for(const n of t[r])e.push({op:n.op,content:{field:o,value:n.range}})}}},4973:(t,e,n)=>{"use strict";n.d(e,{z9:()=>h,dq:()=>f,uK:()=>d});var r=n(1881),s=n(1169),o=n(9064),i=n(7011);async function a(t,e){const n=[];let r=null,s=null;for(const o of e.map((e=>e[t.id]))){if(t.values?.[o]?.uncomputable)continue;const e=Number(o);Number.isFinite(e)&&(n.push(e),null===r?r=s=e:(r=Math.min(r,e),s=Math.max(s,e)))}const a=(0,o.Z)().domain([r,s]).range([10,510]),l=(0,i.q)(a,{values:n},!0,20);if(!Array.isArray(l.bins))throw"getBinsDensity does not return []";if(0==l.bins.length)throw"getBinsDensity returns an empty array";return{minvalue:r,maxvalue:s,densityMax:l.densityMax,density:l.bins,samplecount:n.length,unit:t.unit,ticks:20}}n(3345);var l=n(2273),c=n(4065),u=n(2974);const f=".";function d(t){const e=t.variant2samples;if(e){if(e.type_samples="samples",e.type_sunburst="sunburst",e.type_summary="summary",!e.variantkey)throw".variantkey missing from variant2samples";if(-1==["ssm_id"].indexOf(e.variantkey))throw"invalid value of variantkey";if(e.twLst){if(!Array.isArray(e.twLst))throw"variant2samples.twLst[] is not array";if(0==e.twLst.length)throw"variant2samples.twLst[] empty array";if(!t.cohort||!t.cohort.termdb)throw"ds.cohort.termdb missing when variant2samples.twLst is in use";for(const n of e.twLst){if(!n.id)throw"tw.id missing from one of variant2samples.twLst[]";const e=t.cohort.termdb.q.termjsonByOneid(n.id);if(!e)throw"term not found for one of variant2samples.twLst: "+n.id;if(n.term=e,!n.q)throw"tw.q{} missing for one of variant2samples.twLst: "+n.id}}if(e.sunburst_twLst){if(!Array.isArray(e.sunburst_twLst))throw".sunburst_twLst[] not array from variant2samples";if(0==e.sunburst_twLst.length)throw".sunburst_twLst[] empty array from variant2samples";if(!t.cohort||!t.cohort.termdb)throw"ds.cohort.termdb missing when variant2samples.sunburst_twLst is in use";for(const n of e.sunburst_twLst){if(!n.id)throw"tw.id missing from one of variant2samples.sunburst_twLst[]";const e=t.cohort.termdb.q.termjsonByOneid(n.id);if(!e)throw"term not found for one of variant2samples.sunburst_twLst: "+n.id;if(n.term=e,!n.q)throw"tw.q{} missing for one of variant2samples.sunburst_twLst: "+n.id}}if(e.gdcapi);else{let e=!1;if(t.queries?.snvindel?.byrange?._tk?.samples&&(e=!0),t.queries?.svfusion?.byrange?.samples&&(e=!0),!e)throw"cannot find a sample source from ds.queries{}"}e.get=async e=>await async function(t,e){!function(t,e){if("samples"==t.get){const n=e.queries?.snvindel?.byrange;n&&(n.bcffile||n.chr2bcffile)&&n._tk.format&&(t.addFormatValues=!0)}}(t,e);const n=await async function(t,e){const n=t.twLst?t.twLst.slice():[];if(e.variant2samples.gdcapi)return await(0,s.nD)(t,n,e,t.geneTwLst);if(t.ssm_id_lst)return await async function(t,e,n){const r=new Map;for(const e of t.ssm_id_lst.split(",")){const s=e.split(f);if(4!=s.length){if(6!=s.length)throw"unknown format of ssm id";{if(!n.queries.svfusion||!n.queries.svfusion.byrange)throw"queries.svfusion.byrange missing when id has 6 fields";const[e,o,i,a,c,u]=s,f=decodeURIComponent(u),d=Number(e);if(d!=l.dtsv&&d!=l.dtfusionrna)throw"dt not sv/fusion";const p=Number(i);if(Number.isNaN(p))throw"position not integer";const m=Number(c);if(Number.isNaN(m))throw"pairlstIdx not integer";const g=Object.assign({},t,{rglst:[{chr:o,start:p,stop:p+1}]}),y=await n.queries.svfusion.byrange.get(g);for(const t of y)t.dt==d&&t.pos==p&&t.strand==a&&t.pairlstIdx==m&&t.mname==f&&h(t.samples,r,t.ssm_id)}}else{if(!n.queries.snvindel||!n.queries.snvindel.byrange)throw"queries.snvindel.byrange missing when id has 4 fields";const[e,o,i,a]=s,l=Number(o);if(Number.isNaN(l))throw"no integer position for snvindel from ssm id";const c=Object.assign({},t,{rglst:[{chr:e,start:l,stop:l}]}),u=await n.queries.snvindel.byrange.get(c);for(const t of u)t.pos==l&&t.ref==i&&t.alt==a&&h(t.samples,r,t.ssm_id)}}return p(r,e,n),{samples:[...r.values()]}}(t,n,e);if(t.rglst)return await m(t,n,e);if(t.geneTwLst){if("object"!=typeof t.genome)throw"serverside genome obj needed";t.rglst=[];for(const e of t.geneTwLst)if(e.term.chr&&e.term.start&&e.term.stop)t.rglst.push({chr:e.term.chr,start:e.term.start,stop:e.term.stop});else{const n=c.S(t.genome,{deep:1,input:e.term.name});if(n.gmlst){const e=n.gmlst[0];t.rglst.push({chr:e.chr,start:e.start,stop:e.stop})}}const r=await m(t,n,e);return delete t.rglst,{samples:r}}if(!e?.cohort?.termdb)throw"unable to do sql query: .cohort.termdb missing for ds";const r={ds:e,filter:t.filter||t.filterObj},o=await(0,u.gh)(r,t.twLst),i=[];for(const e in o.samples){const 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e.queries.snvindel.byrange.get(n)),a=function(t,e,n){const[r,s]=n.details.groups,o=[];for(const n of t){n.groupData=[{refCount:n._refCount,altCount:n._altCount}];const t=e.find((t=>t.chr==n.chr&&t.pos==n.pos&&t.ref==n.ref&&t.alt==n.alt));t?n.groupData.push({refCount:t._refCount,altCount:t._altCount}):n.groupData.push({refCount:0,altCount:0}),o.push(n)}for(const n of e){t.find((t=>t.chr==n.chr&&t.pos==n.pos&&t.ref==n.ref&&t.alt==n.alt))||(n.groupData=[{refCount:0,altCount:0},{refCount:n._refCount,altCount:n._altCount}],o.push(n))}return o}(o.mlst,i.mlst,t);return{mlst:a,totalSampleCount_group1:M(o.mlst),totalSampleCount_group2:M(i.mlst)}}n.filterObj=C(t);const o=await e.queries.snvindel.byrange.get(n),i=T(o);"filter"==r.type?i.totalSampleCount_group1=M(o):"filter"==s?.type&&(i.totalSampleCount_group2=M(o));return i}(t,n);if(1==t.details.groups.length)j(n,s.mlst,t.details.groups[0]);else{if(2!=t.details.groups.length)throw"q.details.groups.length not 1 or 2";await async 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n=[t.filter];if(e)n.push(e);else for(const e of t.details.groups)"filter"==e.type&&n.push(e.filter);return(0,N.xH)(n)}function j(t,e,n){if("filter"!=n.type)if("info"!=n.type){if("population"!=n.type)throw"unknown type of single group";{const r=t.queries.snvindel.populations.find((t=>t.key==n.key));if(!r)throw"unknown population";for(const t of e){let e=0,n=0;for(const s of r.sets)e+=Number(t.info[s.infokey_AC]||0),n+=Number(t.info[s.infokey_AN]||0);t.nm_axis_value=e/n}}}else{if(!n.infoKey)throw"infoKey missing on single group.type=info";for(const t of e){const e=t.info[n.infoKey];if(null==e);else{const n=Number(e);Number.isNaN(n)||(t.nm_axis_value=n)}}}else for(const t of e)t.nm_axis_value=Number((t._altCount/(t._altCount+t._refCount)).toPrecision(2))}function E(t){let e=0,n=0;for(const r of t.samples){if(!r?.formatK2v?.GT)continue;const s=r.formatK2v.GT.split("/").map(Number);n+=s.length;for(const n of s)n==t.altAlleleIdx&&e++}return[e,n]}function O(t,e,n){const[r,s]=e.groups;j(t,n,r);const o=n.map((t=>t.nm_axis_value));j(t,n,s);for(const[t,e]of n.entries())e.nm_axis_value=o[t]-e.nm_axis_value}function I(t,e,n,r){const s=[];for(const o of e.groups)if("info"!=o.type)if("filter"!=o.type){if("population"!=o.type)throw"unknown group.type";{if(!o.key)throw"group.key missing for type=population";const e=t.queries.snvindel.populations.find((t=>t.key==o.key));if(!e)throw"invalid group.key for population";const i=new Map;for(const t of e.sets)i.set(t.key,{ACraw:Number(n.info[t.infokey_AC]||0),ANraw:Number(n.info[t.infokey_AN]||0)});let a=0,l=0;if(o.adjust_race)[a,l]=R(i,r);else for(const t of i.values())l+=t.ACraw,a+=t.ANraw-t.ACraw;s.push({altCount:l,refCount:a})}}else s.push({altCount:n._altCount,refCount:n._refCount});else{if(!o.key)throw"group.key missing for type=info";s.push({value:n.info[o.key]})}return s}function R(t,e){let n=0;for(const e of t.values())n+=e.ANraw;let r=0,s=0;for(const[o,i]of 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async function(t,e,n,r,s){const o={equals:[],startsWith:[],startsWord:[],includes:[]},i=decodeURIComponent(t.findterm).toUpperCase(),a=[];try{if("snp"==t.targetType){if(!r.queries?.snvindel?.allowSNPs)throw"this dataset does not support snp search";const t=await(0,D.SC)({byName:!0,lst:[i.toLowerCase()]},s);for(const e of t)a.push({type:"geneVariant",name:e.name,subtype:"snp",chr:e.chrom,start:e.chromStart,stop:e.chromEnd,alleles:e.alleles})}else{const e=(0,k.CG)({type:"geneVariant"},t.usecase).has("plot");if(r.mayGetMatchingGeneNames&&e&&await r.mayGetMatchingGeneNames(o,i,t),r.queries?.defaultBlock2GeneMode&&e)try{const t=(0,P.S)(s,{input:i});if(Array.isArray(t.hits))for(let e=0;e<7&&t.hits[e];e++)a.push({name:t.hits[e],type:"geneVariant"})}catch(t){}}const l=await n.q.findTermByName(i,L,t.cohortStr,t.treeFilter,t.usecase,o);a.push(...l.map(Z));a.forEach((t=>{"geneVariant"!=t.type&&(t.__ancestors=n.q.getAncestorIDs(t.id),t.__ancestorNames=n.q.getAncestorNames(t.id))})),e.send({lst:a})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}}(r,n,l,o,s);if(r.getterminfo)return function(t,e,n){if(!t.tid)throw"no term id";e.send({terminfo:n.q.getTermInfo(t.tid)})}(r,n,l);if(r.phewas)return r.update?await u.update_image(r,n):r.getgroup?await u.getgroup(r,n):await u.trigger(r,n,o);if(r.gettermdbconfig)return a(r,n,o,s);if(r.getcohortsamplecount)return n.send({count:o.cohort.termdb.q.getcohortsamplecount(r.cohort)});if(r.getsamplecount)return n.send(await async function(t,e,n){const r=i.i.canDisplaySampleIds(t,n);if("list"==e.getsamplecount){return await c.cf(e.filter,n,r)}return await c.B9(e,n)}(e,r,o));if(r.getsamples)return await async function(t,e,n){const r=await c.cf(t.filter,n),s=r.map((t=>n.cohort.termdb.q.id2sampleName(t)));e.send({samples:s})}(r,n,o);if(r.getcuminc)return await async function(t,e,n){const r=await(0,f.g)(t,n);e.send(r)}(r,n,o);if(r.getsurvival)return await async function(t,e,n){const r=await v(t,n);e.send(r)}(r,n,o);if(r.getregression)return await async function(t,e,n){const r=await(0,_.j)(t,n);e.send(r)}(r,n,o);if(r.validateSnps)return n.send(await(0,x.G)(r,l,o,s));if(r.getvariantfilter)return function(t,e){if(e.track)return void t.send(e.track.variant_filter);t.send(e?.queries?.snvindel?.variant_filter||{})}(n,o);if(r.getLDdata)return await async function(t,e,n){if(!t.ldtkname)throw".ldtkname missing";if(!e.queries?.ld?.tracks)throw"no ld tk";const r=e.queries.ld.tracks.find((e=>e.name==t.ldtkname));if(!r)throw"unknown ld tk";if("object"!=typeof t.m)throw"q.m{} not object";if(!t.m.chr)throw"q.m.chr missing";if(!Number.isInteger(t.m.pos))throw"q.m.pos not integer";if(!t.m.ref||!t.m.alt)throw"q.m{} invalid alleles";const s=t.m.ref+"."+t.m.alt,o=(r.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+t.m.pos+"-"+(t.m.pos+1),i=[];await(0,m.UE)({args:[r.file,o],dir:r.dir,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),a=n[3],l=n[4],c=Number.parseFloat(n[5]);r==t.m.pos&&a==s?i.push({pos:o,alleles:l,r2:c}):o==t.m.pos&&l==s&&i.push({pos:r,alleles:a,r2:c})}}),n.send({lst:i})}(r,o,n);if(r.genesetByTermId)return function(t,e,n){if(!n.termMatch2geneSet)throw"this feature is not enabled";if("string"!=typeof t.genesetByTermId||0==t.genesetByTermId.length)throw"invalid query term id";const r=n.q.getGenesetByTermId(t.genesetByTermId);e.send(r)}(r,n,l);if(r.getSampleScatter&&(r.for="scatter"),"scatter"==r.for)return await(0,q.uR)(e,r,n,o,s);if(r.getLowessCurve)return await(0,q.v8)(e,r,n);if(r.getCohortsData)return await async function(t,e,n){const r=function(t){const e=t.cohort.db.connection.prepare("select * from features").all();return{cohorts:t.cohort.db.connection.prepare("select * from cohorts where cohort in (select distinct(cohort) from cohort_features)\n\t\t order by sample_count desc").all(),features:e,cfeatures:t.cohort.db.connection.prepare("select * from cohort_features").all()}}(n);e.send(r)}(0,n,o);if("mds3queryDetails"==r.for)return function(t,e){const n={},r=e.queries||{};r.snvindel&&(n.snvindel={},r.snvindel.details&&(n.snvindel.details=r.snvindel.details),r.snvindel.populations&&(n.snvindel.populations=r.snvindel.populations));r.trackLst&&(n.trackLst=r.trackLst);if(r.ld){n.ld=JSON.parse(JSON.stringify(r.ld));for(const t of n.ld.tracks)delete t.file}t.send(n)}(n,o);if("termTypes"==r.for)return n.send(await o.getTermTypes(r));if("matrix"==r.for)return await async function(t,e,n,r,s){if(t.getPlotDataByName){if(!r.cohort?.matrixplots?.plots)throw"ds.cohort.matrixplots.plots missing for the dataset";const e=r.cohort.matrixplots.plots.find((e=>e.name===t.getPlotDataByName));if(!e)throw"invalid name of premade matrix plot";return void n.send(e.matrixConfig)}const o=await(0,p.Yu)(t,r,s);if(i.i.canDisplaySampleIds(e,r))for(const t of Object.values(o.samples))t.sampleName=r.sampleId2Name.get(t.sample);n.send(o)}(r,e,n,o,s);if("getSamplesPerFilter"==r.for)return await(0,p.fZ)(r,o,n);if("mds3variantData"==r.for)return await A(r,n,o);if(r.for,"convertSampleId"==r.for)return function(t,e,n){if(!n.convertSampleId)throw"not supported on this ds";if(!Array.isArray(t.inputs))throw"q.inputs[] not array";e.send({mapping:n.convertSampleId.get(t.inputs)})}(r,n,l);if("singleSampleData"==r.for)return async function(t,e,n,r,s){const o=i.i.canDisplaySampleIds(e,r);let a=[];if(o)try{a=s.q.getSingleSampleData(t.sampleId,t.term_ids),n.send(a)}catch(t){n.send({error:t.message||t})}else n.send({error:"Requires sign in to access the sample data"})}(r,e,n,o,l);if("getProfileFacilities"==r.for)return async function(t,e,n,r,s){const o=i.i.canDisplaySampleIds(e,r);let 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k(t,e,n){if(!t.q.restrictAncestry)return;if(!("name"in t.q.restrictAncestry))throw".name missing from tw.q.restrictAncestry";if(!n.cohort.termdb.restrictAncestries)throw"ds.cohort.termdb.restrictAncestries missing";const r=n.cohort.termdb.restrictAncestries.find((e=>e.name==t.q.restrictAncestry.name));if(!r)throw"unknown ancestry for restriction: "+t.q.restrictAncestry.name;if(r.pcs)t.q.restrictAncestry.pcs=r.pcs;else{if(!r.PCBySubcohort)throw"unknown way of accessing pcs from ds.cohort.termdb.restrictAncestries: "+t.q.restrictAncestry.name;{if(!e.filter)throw"q.filter missing while trying to access subcohort for PCBySubcohort";const n=O(e.filter,"cohortFilter");if(!n)throw"tvs by tag=cohortFilter missing from q.filter.lst[] while trying to access subcohort for PCBySubcohort";const s=n.tvs.values.map((t=>t.key)).sort().join(","),o=r.PCBySubcohort[s];if(!o)throw"unknown key for PCBySubcohort: "+s;if(!o.pcs)throw"pcs Map() missing from PCBySubcohort[]: 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n.name}if("custom-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!t.q.groupsetting.customset)throw"outcome.q.customset missing";const e=t.q.groupsetting.customset.groups.find((e=>e.name!=t.refGrp));if(!e)throw"non-ref group not found for custom-groupset";return e.name}if("values"==t.q.type){if(!t.term.values)throw"outcome.term.values{} missing";for(const e in t.term.values){const n=t.term.values[e];if(n.label!=t.refGrp)return n.label}throw"unknown nonref group from outcome.term.values"}if("custom-bin"==t.q.type){const e=t.q.lst.find((e=>e.label!=t.refGrp));if(!e)throw"non-ref bin is not found for custom-bin";return e.label}if("regular-bin"==t.q.type)throw"do not know a way to find computed bin list for type=regular-bin";throw"unknown outcome.q.type"}async function A(t,e,n,r){v=(new Date).getTime();const o=s().join(h().cachedir,Math.random().toString()+".json");await p.Sf(o,JSON.stringify(t));const 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e={},[r,s]=t.shift().split(":");e.term1=n[r],e.term2=n[s],e.lst=t,o.data.type3.interactions.push(e)}else{const e=n[t.shift()];o.data.type3.terms[e]||(o.data.type3.terms[e]=t)}if(o.data.type3.label="Type III statistics",i.totalSnpEffect){if(1!=i.totalSnpEffect.rows.length)throw"total SNP effect table should have 1 row";o.data.totalSnpEffect={header:i.totalSnpEffect.header.slice(0,4)};const t=i.totalSnpEffect.rows[0].slice(0,4),e=i.totalSnpEffect.rows[0][4].split(";"),r=e.findIndex((t=>!t.includes(":"))),s=e.splice(r,1)[0];o.data.totalSnpEffect.snp=n[s];const a=[];for(const t of e){if(!t.includes(":"))throw"expected interaction";const[e,r]=t.split(":");a.push({term1:n[e],term2:n[r]})}o.data.totalSnpEffect.interactions=a,o.data.totalSnpEffect.lst=t,o.data.totalSnpEffect.label="Total SNP effect"}i.tests&&(o.data.tests=i.tests,o.data.tests.label="Statistical tests"),o.data.other=i.other,o.data.other.label="Other summary statistics";for(const e of 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o={time:e.outcome_time,event:e.outcome_event},l=i.samples.get(r);if(!l)continue;const[c,u]=l.split("/");o.series=i.effAle==c||i.effAle==u?"1":"2",t.push(o)}new Set(t.map((t=>t.series))).size<2?o.add(r):s.data[r]=t}const i=await(0,g.y)(s);let a;for(const[e,n]of t.lowAFsnps){if(o.has(e)){a={pvalue:"NA",msg:"Cannot perform cumulative incidence test on this snp - at least one allele is not found in any sample"}}else{if(1==!i[e].tests?.length)throw"must have a single test";const t=Number(i[e].tests[0].pvalue);if(!Number.isFinite(t))throw"invalid pvalue";a={pvalue:Number(t.toFixed(4)),ci_data:{[e]:i[e]}}}const n={id:e,AFstr:t.snpid2AFstr.get(e),data:{headerRow:T(e,t),cuminc:a}};r.resultLst.push(n)}}(o,e,n,r)}w=(new Date).getTime(),_.NodeJS.snplocusPostprocess=(w-v)/1e3+" sec"}}function T(t,e){const n=e.snpgt2count.get(t);if(!n)return{k:"Error",v:"Variant not found"};const r=[];for(const[t,e]of n)r.push(t+"="+e);const s={snpid:t,gtcounts:r};return 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l(t){if(!t.cohort)throw"ds.cohort missing";if(!t.cohort.db)throw"ds.cohort.db missing";if(!t.cohort.termdb)throw"ds.cohort.termdb missing";const e=t.cohort.db.file_fullpath||t.cohort.db.file;if(!e)throw"both file and file_fullpath missing";let n;try{console.log("Connecting",e),n=(0,o.sE)(e),console.log(`DB connected for ${t.label}: ${e}`)}catch(t){throw`Cannot connect db ${e}: ${t.message||t}`}t.cohort.db.connection=n;const r=c(n),l=["cohorts","sampleidmap","terms","ancestry","alltermsbyorder","termhtmldef","category2vcfsample","chronicevents","precomputed_chc_grade","precomputed_chc_child","precomputed_cuminc","precomputed_cox","subcohort_terms","subcohort_samples","survival","features","cohort_features","anno_integer","anno_float","anno_categorical","buildDate"];for(const t of l)r.has(t)||console.log(`${t} table missing!!!!!!!!!!!!!!!!!!!!`);if(!r.has("terms"))throw"terms table missing";if(!r.has("ancestry"))throw"ancestry table 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f.getcohortsamplecount=()=>o}if(r.has("category2vcfsample")){const t=n.prepare("SELECT * FROM category2vcfsample");let e;f.getcategory2vcfsample=()=>{if(e)return e;e=t.all();for(const t of e)t.q=JSON.parse(t.q),t.categories=JSON.parse(t.categories);return e}}if(r.has("alltermsbyorder")){const t=n.prepare("SELECT * FROM alltermsbyorder");let e;f.getAlltermsbyorder=()=>{if(e)return e;const n=t.all();e=[];for(const t of n){const n=f.termjsonByOneid(t.id);n&&e.push({group_name:t.group_name,term:n})}return e}}{const t=n.prepare("SELECT name, jsondata FROM terms WHERE id=?"),e=new Map;f.termjsonByOneid=n=>{if(e.has(n))return e.get(n);const r=t.get(n);if(r){const t=JSON.parse(r.jsondata);return t.id=n,t.name=r.name||t.name,e.set(n,t),t}}}{const t=n.prepare("select id from terms where parent_id=?"),e=new Map;f.termIsLeaf=n=>{if(e.has(n))return e.get(n);let r=!0;const s=t.get(n);return s&&s.id&&(r=!1),e.set(n,r),r}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types, 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n&&(r=f.termjsonByOneid(n)),t.set(e,r),r}}}{const t=n.prepare("SELECT id, name, type, jsondata, s.included_types, s.child_types \n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=? \n\t\t\tWHERE id IN (SELECT id FROM terms WHERE parent_id=?)\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),e=new Map;f.getTermChildren=(n,r="")=>{const s=n+";;"+r;if(e.has(s))return e.get(s);const o=t.all([r,n]);let i;return o&&(i=o.map((t=>{const e=JSON.parse(t.jsondata);return e.id=t.id,e.name=t.name||e.name,e.included_types=t.included_types?t.included_types.split(","):[],e.child_types=t.child_types?t.child_types.split(","):[],e}))),e.set(s,i),i}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE name LIKE ?");f.findTermByName=(e,n=10,r="",s=null,o=null,a=null)=>{const l=t.all([r,"%"+e+"%"]);if(l){const t=a||{equals:[],startsWith:[],startsWord:[],includes:[]};for(const n of l){if(!n.jsondata)continue;const r=n.name.toLowerCase(),s=JSON.parse(n.jsondata);s.id=n.id,s.name=n.name||s.name,s.included_types=n.included_types?n.included_types.split(","):[],o&&!(0,i.CG)(s,o).has("plot")||(r===e?t.equals.push(s):r.startsWith(e)?t.startsWith.push(s):r.includes(" "+e)?t.startsWord.push(s):t.includes.push(s))}return[...t.equals,...t.startsWith,...t.startsWord,...t.includes].slice(0,n)}}}{const t=n.prepare("SELECT MAX(value) AS v FROM anno_integer WHERE term_id=?"),e=n.prepare("SELECT MAX(value) AS v FROM anno_float WHERE term_id=?"),r=new Map;f.findTermMaxvalue=(n,s)=>{if(r.has(n))return r.get(n);const o=(s?t:e).get(n);return o?(r.set(n,o.v),o.v):void 0}}{const t={float:n.prepare("SELECT sample,value FROM anno_float WHERE term_id=?"),integer:n.prepare("SELECT sample,value FROM anno_integer WHERE term_id=?"),categorical:n.prepare("SELECT sample,value FROM anno_categorical WHERE 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AND t.id=a.ancestor_id"),e=new Map;f.getAncestorNames=n=>{if(e.has(n))return e.get(n);const r=t.all(n).map((t=>t.name));return e.set(n,r),r}}{const t={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=?")},e={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=? AND sample=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=? AND sample=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=? AND sample=?")},r={categorical:n.prepare("SELECT value FROM anno_categorical a,sampleidmap s WHERE term_id=? AND s.name=?"),integer:n.prepare("SELECT value FROM anno_integer a,sampleidmap s WHERE term_id=? AND s.name=?"),float:n.prepare("SELECT value FROM anno_float a, sampleidmap s WHERE term_id=? AND s.name=?")};f.getSample2value=(n,s=null)=>{const o=f.termjsonByOneid(n);return s?"string"==typeof s?r[o.type].all(n,s):e[o.type].all(n,s):t[o.type].all(n)}}if(r.has("termhtmldef")){const t=n.prepare("SELECT jsonhtml FROM termhtmldef WHERE id=?"),e=new Map;f.getTermInfo=n=>{if(e.has(n))return e.get(n);const r=t.get(n);if(r){const t=JSON.parse(r.jsonhtml);return t.id=n,e.set(n,t),t}}}f.getSupportedChartTypes=e=>{u(t);s().dsCredentials?.[t.label];const n={},r={};for(const o of t.cohort.termdb.termtypeByCohort)if(o.type){if(!(o.cohort in n)){n[o.cohort]=new Set(["regression","summary"]),t.cohort.scatterplots&&n[o.cohort].add("sampleScatter"),r[o.cohort]=0,t.cohort.allowedChartTypes?.includes("matrix")&&n[o.cohort].add("matrix");const s=a.i.getForbiddenRoutesForDsEmbedder(t.label,e);s.includes("termdb")||s.includes("*")||(n[o.cohort].add("dataDownload"),n[o.cohort].add("sampleView"),t.queries?.singleCell&&n[o.cohort].add("singleCellPlot"))}s().features?.draftChartTypes&&n[o.cohort].add(...s().features.draftChartTypes),"survival"!=o.type||n[o.cohort].has("survival")||n[o.cohort].add("survival"),"condition"!=o.type||n[o.cohort].has("cuminc")||n[o.cohort].add("cuminc"),"float"!=o.type&&"integer"!=o.type||(r[o.cohort]+=o.samplecount)}for(const t in r)r[t]>1&&n[t].add("sampleScatter");for(const t in n)n[t]=[...n[t]];if(t.cohort.allowedChartTypes)for(const e in n)n[e]=n[e].filter((e=>t.cohort.allowedChartTypes.includes(e)));if(t.queries){if(t.queries.snvindel||t.queries.trackLst)for(const t in n)n[t].push("genomeBrowser");if(t.queries.geneExpression)for(const t in n)n[t].push("hierCluster");if(t.queries.rnaseqGeneCount)for(const t in n)n[t].push("DEanalysis")}return n},f.getSingleSampleData=function(t,e=[]){const r=e.length?`and term_id in (${e.map((t=>"?")).join(",")})`:"",s=`select term_id, value, jsondata from ( select term_id, value \n\t\tfrom anno_categorical \n\t\twhere sample=? ${r}\n\t\tunion all \n\t\tselect term_id, \n\t\tvalue from anno_float \n\t\twhere sample=? ${r}\n\t\tunion all  \n\t\tselect term_id, value \n\t\tfrom anno_integer \n\t\twhere sample=? ${r}\n\t\tunion all \n\t\tselect term_id, (min_years_to_event || ' ' || value) as value \n\t\tfrom precomputed_chc_grade \n\t\twhere max_grade=1 and sample=? ${r}\n\t\tunion all \n\t\tselect term_id, (tte || ' ' || exit_code) as value \n\t\tfrom survival \n\t\twhere sample=? ${r}) join terms on terms.id = term_id`;return n.prepare(s).all([t,...e,t,...e,t,...e,t,...e,t,...e])},f.getProfileFacilities=function(){return n.prepare("select name from sampleidmap join \n\t\tanno_categorical on sampleidmap.id = anno_categorical.sample\n\t\twhere term_id = 'sampleType' and value = 'Facility'").all()}}function c(t){const e=t.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(e.map((t=>t.name)))}function u(t){if(t.cohort.termdb.termtypeByCohort){if(!Array.isArray(t.cohort.termdb.termtypeByCohort))throw"termtypeByCohort is not array"}else{if(!t.cohort?.db?.connection)throw"termtypeByCohort[] not set but cohort.db.connection missing";t.cohort.termdb.termtypeByCohort=t.cohort.db.connection.prepare("WITH c AS (\n\t\t\tSELECT cohort, term_id\n\t\t\tFROM subcohort_terms s\n\t\t\tGROUP BY cohort, term_id\n\t\t) \n\t\tSELECT cohort, type, count(*) as samplecount\n\t\tFROM terms t\n\t\tJOIN c ON c.term_id = t.id\n\t\tGROUP BY cohort, type").all()}}},3795:(t,e,n)=>{"use strict";n.d(e,{G:()=>g,u:()=>y});var r=n(7147),s=n.n(r),o=n(1017),i=n.n(o),a=n(3345),l=n(8907),c=(n(2826),n(4521),n(334)),u=n.n(c),f=n(3625);const d="%CHROM\t%POS\t%REF\t%ALT[\t%TGT]\n",h="%POS\t%ID\t%REF\t%ALT\t%INFO[\t%TGT]\n",p="./.",m=1e3;async function g(t,e,n,r){try{if(t.sumSamples)return await async 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i)l.push({allele:t,count:i[t],isRef:t==r});d.push({snpid:n,alleles:l,gt2count:a})}return{numOfSampleWithAnyValidGT:f.size,snps:d}}(t,0,n);if(t.snptext)return await async function(t,e,n){if(!n.snp)throw"snp not supported by genome";if(!t.snptext)throw".snptext missing";const r=function(t){const e=[];for(const n of t.trim().split("\n")){const[t,r]=n.trim().split(/[\s\t]/);if(t&&t.startsWith("rs")){if(e.find((e=>e.rsid==t)))continue;const n={rsid:t,snpid:t};r&&(n.effectAllele=r),e.push(n)}else e.push({rsid:t,snpid:t,invalid:"INVALID RSID"})}return e}(t.snptext);if(!r.length)throw"no snps";await async function(t,e){for(const n of t)if(!n.invalid)if(n.chr&&"string"==typeof n.chr){const t=e.chrlookup[n.chr.toUpperCase()];if(!t){n.invalid=!0;continue}if(!Number.isInteger(n.pos)){n.invalid=!0;continue}if(n.pos<=0||n.pos>=t.len){n.invalid=!0;continue}}else if(n.rsid){const t=await a.mr(e.snp.bigbedfile,n.rsid),r=[];for(const n of t){const t=n.split("\t"),s=e.chrlookup[t[0].toUpperCase()];s&&s.major&&r.push(t)}if(0==r.length){n.invalid=!0;continue}const s=r[0];n.chr=s[0],n.pos=Number.parseInt(s[1]),n.dbsnpRef=s[4],n.dbsnpAlts=s[6].split(",").filter(Boolean)}else n.invalid=!0;if(!t.find((t=>!t.invalid)))throw"no valid variants"}(r,n);const o=await async function(t,e,n){let r;if(n.track){if(r=n.track.vcf,!r)throw"ds.track.vcf missing"}else r=n.queries.snvindel.byrange._tk;const o=new Set,l=[];for(const t of e){if(t.invalid)continue;let e;if(r.chr2files){if(e=r.chr2files?.[t.chr].file,!e)throw"chr not in chr2files"}else if(r.chr2bcffile){if(e=r.chr2bcffile[t.chr],!e)throw"chr not in chr2bcffile"}else e=r.file||r.url;o.add(e);const n=(r.nochr?t.chr.replace("chr",""):t.chr)+"\t"+(t.pos+1);l.push(n)}const c=i().join(u().cachedir,await a.tG(l.join("\n"))),f=i().join(u().cachedir,await a.tG([...o].join("\n")));await a.UE({isbcf:!0,args:["query","-R",c,"-f",d,"-v",f],dir:r.dir,callback:t=>{const n=t.split("\t"),s=(r.nochr?"chr":"")+n[0],o=n[1],i=n[2],a=n[3].split(","),l=e.find((t=>{if(t.chr==s&&t.pos===o-1&&t.dbsnpRef==i&&t.dbsnpAlts.some((t=>a.includes(t))))return t}));if(l){l.referenceAllele=i,l.altAlleles=a,l.gtlst=[];for(let t=4;t<n.length;t++)l.gtlst.push(n[t]==p?"":n[t])}}}),s().unlink(c,(()=>{})),s().unlink(f,(()=>{}));const h=["snpid\tchr\tpos\tref\talt\teff\t"+r.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid||t.gtlst&&(h.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele||"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const m=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random());return await a.Sf(i().join(u().cache_snpgt.dir,m),h.join("\n")),m}(t,r,e);return{snps:r,cacheid:o}}(t,n,r);if(t.chr)return await async function(t,e,n){const r=Number(t.start),s=Number(t.stop);if(!Number.isInteger(r)||!Number.isInteger(s))throw"start/stop are not integers";if(r>s||r<0)throw"invalid start/stop coordinate";let o,l;if(e.track){if(o=e.track.vcf,!o)throw"ds.track.vcf missing";if(l=o.chr2bcffile[t.chr],!l)throw"chr not in chr2bcffile"}else if(o=e.queries.snvindel.byrange._tk,l=o.chr2files?o.chr2files?.[t.chr].file:o.file||o.url,!l)throw"no bcf file";const c=(o.nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+s,d=["query",l,"-r",c,"-f",h];t.variant_filter&&y(t.variant_filter,d);const g={snps:[]},b=["snpid\tchr\tpos\tref\talt\teff\t"+o.samples.map((t=>t.name)).join("\t")];return await a.UE({isbcf:!0,args:d,dir:o.dir,callback:(e,n)=>{if(g.snps.length>=m)return n.kill(),void(g.reachedVariantLimit=!0);const r=e.split("\t"),s=Number(r[0])-1,i=r[1],a=r[2],l=r[3].split(","),c=i&&"."!=i?i:s+"."+a+"."+l.join(","),u={snpid:c,chr:t.chr,pos:s};(0,f.H)(o,a,l,u,r[4],r[1]);for(const t of u.mlst)t.vcf_id&&(t.mname=t.vcf_id);g.snps.push(u);const d=[c,t.chr,s,a,l.join(","),""];for(let t=5;t<r.length;t++)d.push(r[t]==p?"":r[t]);b.push(d.join("\t"))}}),g.cacheid=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random()),await a.Sf(i().join(u().cache_snpgt.dir,g.cacheid),b.join("\n")),g}(t,n);throw"unknown how to validate"}catch(t){return t.stack&&console.log(t.stack),{error:t.message||t}}}function y(t,e){const n=[];for(const e of t.lst)if(e.tvs.values){const t=e.tvs.isnot?"!=":"=";for(const r of e.tvs.values){const s=isNaN(r.key)?`"${r.key}"`:Number(r.key);n.push(`INFO/${e.tvs.term.id}${t}${s}`)}}else{if(!e.tvs.ranges)throw`unknown tvs spec for info_field: type=${e.type}, term.id=${e.tvs.term.id}`;for(const t of e.tvs.ranges)"start"in t&&n.push(`INFO/${e.tvs.term.id} ${t.startinclusive?">=":">"} ${t.start}`),"stop"in t&&n.push(`INFO/${e.tvs.term.id} ${t.stopinclusive?"<=":"<"} ${t.stop}`)}0!=n.length&&e.push("-i",n.join(" && "))}},8907:(t,e,n)=>{"use strict";n.d(e,{yT:()=>M,YG:()=>C,g5:()=>S,J4:()=>N,B9:()=>k,cf:()=>x,tt:()=>q,Bi:()=>A,ig:()=>j});var r={};n.r(r),n.d(r,{binary:()=>f,continuous:()=>l,cubicSpline:()=>c,discrete:()=>u});var s={};n.r(s),n.d(s,{groupset:()=>p,values:()=>d});var o={};n.r(o),n.d(o,{binary:()=>g,cox:()=>b,cuminc:()=>y,discrete:()=>m});var i=n(4048),a=n(5257);const l={getCTE(t,e,n,r,s,o,i){s.push(e.id);const a=M(e,r);return s.push(...a.values),{sql:`${t} AS (\n\t\t\t\tSELECT \n\t\t\t\t\tsample,\n\t\t\t\t\tvalue as key, \n\t\t\t\t\tvalue\n\t\t\t\tFROM anno_${e.type}\n\t\t\t\tWHERE term_id=? ${a.clause}\n\t\t\t)`,tablename:t}}},c=l,u={getCTE(t,e,n,r,s,o,i){s.push(e.id);const a=C(r,e,n,o,i),l=[],c=new Map;r.bin_size;for(const t of a)!("name"in t)&&t.label&&(t.name=t.label),c.set(t.name,t),l.push(`SELECT '${t.name}' AS name,\n\t\t\t\t${null==t.start?0:t.start} AS start,\n\t\t\t\t${null==t.stop?0:t.stop} AS stop,\n\t\t\t\t0 AS unannotated,\n\t\t\t\t${t.startunbounded?1:0} AS startunbounded,\n\t\t\t\t${t.stopunbounded?1:0} AS stopunbounded,\n\t\t\t\t${t.startinclusive?1:0} AS 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AS key, ? AS value\n\t\t\t\t\t\tFROM ${l.CTEname}`)}}return{sql:`${a.length?a.join("\n,")+",":""}\n\t\t\t${t} AS (\n\t\t\t\t${i.join("\nUNION ALL\n")}\n\t\t\t)`,tablename:t}}},m={getCTE(t,e,n,r,s){if(r.breaks&&r.breaks.length>0)return w(t,e,r,s);{const[n,o]=v(r);s.push(e.id);const i=M(e,r);return s.push(...i.values),{sql:`${t} AS (\n\t\t\t\t\tSELECT\n\t\t\t\t\t\tsample,\n\t\t\t\t\t\tvalue as key,\n\t\t\t\t\t\tvalue\n\t\t\t\t\tFROM\n\t\t\t\t\t\t${"grade"==n?"precomputed_chc_grade":"precomputed_chc_child"}\n\t\t\t\t\tWHERE\n\t\t\t\t\t\tterm_id = ?\n\t\t\t\t\t\tAND ${o} = 1\n\t\t\t\t\t\t${i.clause}\n\t\t\t\t)`,tablename:t}}}},g={getCTE(t,e,n,r,s){if(1!=r.breaks?.length)throw"binary mode requires one break";return w(t,e,r,s)}},y={getCTE(t,e,n,r,s){if(1!=r.breaks?.length)throw"cuminc mode requires one break";return s.push(e.id,r.breaks[0]),{sql:`${t} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tevent AS key,\n\t\t\t\t\ttime AS value\n\t\t\t\tFROM\n\t\t\t\t\tprecomputed_cuminc\n\t\t\t\tWHERE\n\t\t\t\t\tterm_id = ?\n\t\t\t\t\tAND grade_cutoff = ?\n\t\t\t)`,tablename:t}}},b={getCTE(t,e,n,r,s){if(1!=r.breaks?.length)throw"cox mode requires one break";s.push(e.id,r.breaks[0]);const o=Object.keys(e.values).map(Number),i=Math.max(...o);return{sql:`${t} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tevent AS key,\n\t\t\t\t\tjson_object('age_start', age_start, 'age_end', age_end) AS value\n\t\t\t\tFROM\n\t\t\t\t\tprecomputed_cox\n\t\t\t\tWHERE\n\t\t\t\t\tterm_id = ?\n\t\t\t\t\tAND grade_cutoff = ?\n\t\t\t)`,tablename:t,events:[{event:1,label:`Event (grade ${r.breaks[0]===i?r.breaks[0]:`${r.breaks[0]}-${i}`})`},{event:0,label:"Censored/death"},{event:-1,label:"Event before entry into the cohort"}]}}};function v(t){const e=t.bar_by_children?"child":t.bar_by_grade?"grade":"";if(!e)throw"must set the bar_by_grade or bar_by_children query parameter";const n=t.value_by_max_grade?"max_grade":t.value_by_most_recent?"most_recent":t.value_by_computable_grade?"computable_grade":"";if(!n)throw"must set a valid value_by_*";return[e,n]}function w(t,e,n,r){const[s,o]=v(n);if("grade"!=s)throw"breaks must be used on grade values";const i=[];for(const t of n.groups)i.push(`SELECT sample, ? as key, value\n\t\t\tFROM precomputed_chc_grade\n\t\t\tWHERE\n\t\t\t\tterm_id=?\n\t\t\t\tAND ${o}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${i.join("\nUNION ALL\n")}\n\t\t)`,tablename:t}}const _={getCTE(t,e,n){let r,s,o="";for(const[t,i]of e.q.groups.entries())"in"in i||(i.in=!0),r=i.values.map((t=>t.sampleId)),s=r.map((()=>"?")).join(","),o+=`SELECT id as sample, ? as key, ? as value\n\t\t\t\tFROM sampleidmap\n\t\t\t\tWHERE sample ${i.in?"":"NOT"} IN (${s})\n\t\t\t`,t!=e.q.groups.length-1&&(o+="UNION ALL "),n.push(i.name,i.name,...r);return{sql:`${t} AS (${o})`,tablename:t}}};n(334),n(3345);async function x(t,e,n=!1){const r=await(0,a.w)(t,e),s=e.cohort.db.connection.prepare(r?`WITH ${r.filters} SELECT sample as id, name FROM ${r.CTEname} join sampleidmap on sample = sampleidmap.id`:"SELECT id, name FROM sampleidmap");let o;if(o=r?s.all(r.values):s.all(),n)return o;for(const t of o)delete t.name;return o}async function k(t,e){if(!t.filter)throw"filter missing";let n;if("object"==typeof t.filter)n=t.filter;else{if("string"!=typeof t.filter)throw"q.filter not obj or str";n=JSON.parse(t.filter)}const r=await(0,a.w)(n,e),s=`WITH ${r.filters}\n\t\tSELECT 'FILTERED_COHORT' as subcohort, count(distinct sample) as samplecount \n\t\tFROM ${r.CTEname}`;return e.cohort.db.connection.prepare(s).all(r.values)}async function q(t){const e=t.ds.cohort.termdb.q.termjsonByOneid(t.term_id);if("integer"!=e.type&&"float"!=e.type)throw"term is not numeric";if(!e.values)return[];const n=await(0,a.w)(t.filter,t.ds),r=n?n.values.slice():[];r.push(t.term_id);const s=[];for(const t in e.values)s.push("?"),r.push(Number(t));const o=`\n\t\t${n?"WITH "+n.filters:""}\n\t\tSELECT count(sample) AS samplecount,value\n\t\tFROM anno_${e.type}\n\t\tWHERE term_id=?\n\t\t${n?"AND sample IN "+n.CTEname:""}\n\t\tAND value IN (${s.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(o).all(r)}async function N(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await(0,a.w)(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const s=`\n\t\t${e?"WITH "+e.filters:""}\n\t\tSELECT sample, value\n\t\tFROM anno_${r.type}\n\t\tWHERE term_id=?\n\t\t${e?" 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t=0,e=this._hullStart;t<q;t++)this.hull[t]=e,e=n[e];this.triangles=this._triangles.subarray(0,this.trianglesLen),this.halfedges=this._halfedges.subarray(0,this.trianglesLen)}_hashKey(t,e){return Math.floor(function(t,e){const n=t/(Math.abs(t)+Math.abs(e));return(e>0?3-n:1+n)/4}(t-this._cx,e-this._cy)*this._hashSize)%this._hashSize}_legalize(t){const{_triangles:e,_halfedges:n,coords:r}=this;let s=0,o=0;for(;;){const i=n[t],a=t-t%3;if(o=a+(t+2)%3,-1===i){if(0===s)break;t=Rs[--s];continue}const l=i-i%3,c=a+(t+1)%3,u=l+(i+2)%3,f=e[o],d=e[t],h=e[c],p=e[u];if(Ds(r[2*f],r[2*f+1],r[2*d],r[2*d+1],r[2*h],r[2*h+1],r[2*p],r[2*p+1])){e[t]=p,e[i]=f;const r=n[u];if(-1===r){let e=this._hullStart;do{if(this._hullTri[e]===u){this._hullTri[e]=t;break}e=this._hullPrev[e]}while(e!==this._hullStart)}this._link(t,r),this._link(i,n[o]),this._link(o,u);const a=l+(i+1)%3;s<Rs.length&&(Rs[s++]=a)}else{if(0===s)break;t=Rs[--s]}}return o}_link(t,e){this._halfedges[t]=e,-1!==e&&(this._halfedges[e]=t)}_addTriangle(t,e,n,r,s,o){const i=this.trianglesLen;return this._triangles[i]=t,this._triangles[i+1]=e,this._triangles[i+2]=n,this._link(i,r),this._link(i+1,s),this._link(i+2,o),this.trianglesLen+=3,i}}function Ps(t,e,n,r){const s=t-n,o=e-r;return s*s+o*o}function Ds(t,e,n,r,s,o,i,a){const l=t-i,c=e-a,u=n-i,f=r-a,d=s-i,h=o-a,p=u*u+f*f,m=d*d+h*h;return l*(f*m-p*h)-c*(u*m-p*d)+(l*l+c*c)*(u*h-f*d)<0}function Ls(t,e,n,r,s,o){const i=n-t,a=r-e,l=s-t,c=o-e,u=i*i+a*a,f=l*l+c*c,d=.5/(i*c-a*l),h=(c*u-a*f)*d,p=(i*f-l*u)*d;return h*h+p*p}function $s(t,e,n,r){if(r-n<=20)for(let s=n+1;s<=r;s++){const r=t[s],o=e[r];let i=s-1;for(;i>=n&&e[t[i]]>o;)t[i+1]=t[i--];t[i+1]=r}else{let s=n+1,o=r;zs(t,n+r>>1,s),e[t[n]]>e[t[r]]&&zs(t,n,r),e[t[s]]>e[t[r]]&&zs(t,s,r),e[t[n]]>e[t[s]]&&zs(t,n,s);const i=t[s],a=e[i];for(;;){do{s++}while(e[t[s]]<a);do{o--}while(e[t[o]]>a);if(o<s)break;zs(t,s,o)}t[n+1]=t[o],t[o]=i,r-s+1>=o-n?($s(t,e,s,r),$s(t,e,n,o-1)):($s(t,e,n,o-1),$s(t,e,s,r))}}function zs(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function Zs(t){return t[0]}function Us(t){return t[1]}const Bs=1e-6;class Gs{constructor(){this._x0=this._y0=this._x1=this._y1=null,this._=""}moveTo(t,e){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}`}closePath(){null!==this._x1&&(this._x1=this._x0,this._y1=this._y0,this._+="Z")}lineTo(t,e){this._+=`L${this._x1=+t},${this._y1=+e}`}arc(t,e,n){const r=(t=+t)+(n=+n),s=e=+e;if(n<0)throw new Error("negative radius");null===this._x1?this._+=`M${r},${s}`:(Math.abs(this._x1-r)>Bs||Math.abs(this._y1-s)>Bs)&&(this._+="L"+r+","+s),n&&(this._+=`A${n},${n},0,1,1,${t-n},${e}A${n},${n},0,1,1,${this._x1=r},${this._y1=s}`)}rect(t,e,n,r){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}h${+n}v${+r}h${-n}Z`}value(){return this._||null}}class Js{constructor(){this._=[]}moveTo(t,e){this._.push([t,e])}closePath(){this._.push(this._[0].slice())}lineTo(t,e){this._.push([t,e])}value(){return this._.length?this._:null}}class Hs{constructor(t,[e,n,r,s]=[0,0,960,500]){if(!((r=+r)>=(e=+e)&&(s=+s)>=(n=+n)))throw new Error("invalid bounds");this.delaunay=t,this._circumcenters=new Float64Array(2*t.points.length),this.vectors=new Float64Array(2*t.points.length),this.xmax=r,this.xmin=e,this.ymax=s,this.ymin=n,this._init()}update(){return this.delaunay.update(),this._init(),this}_init(){const{delaunay:{points:t,hull:e,triangles:n},vectors:r}=this,s=this.circumcenters=this._circumcenters.subarray(0,n.length/3*2);for(let e,r,o=0,i=0,a=n.length;o<a;o+=3,i+=2){const a=2*n[o],l=2*n[o+1],c=2*n[o+2],u=t[a],f=t[a+1],d=t[l],h=t[l+1],p=t[c],m=t[c+1],g=d-u,y=h-f,b=p-u,v=m-f,w=2*(g*v-y*b);if(Math.abs(w)<1e-9){let s=1e9;const o=2*n[0];s*=Math.sign((t[o]-u)*v-(t[o+1]-f)*b),e=(u+p)/2-s*v,r=(f+m)/2+s*b}else{const t=1/w,n=g*g+y*y,s=b*b+v*v;e=u+(v*n-y*s)*t,r=f+(g*s-b*n)*t}s[i]=e,s[i+1]=r}let o,i,a,l=e[e.length-1],c=4*l,u=t[2*l],f=t[2*l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],o=c,i=u,a=f,c=4*l,u=t[2*l],f=t[2*l+1],r[o+2]=r[c]=a-f,r[o+3]=r[c+1]=u-i}render(t){const e=null==t?t=new Gs:void 0,{delaunay:{halfedges:n,inedges:r,hull:s},circumcenters:o,vectors:i}=this;if(s.length<=1)return null;for(let e=0,r=n.length;e<r;++e){const r=n[e];if(r<e)continue;const s=2*Math.floor(e/3),i=2*Math.floor(r/3),a=o[s],l=o[s+1],c=o[i],u=o[i+1];this._renderSegment(a,l,c,u,t)}let a,l=s[s.length-1];for(let e=0;e<s.length;++e){a=l,l=s[e];const n=2*Math.floor(r[l]/3),c=o[n],u=o[n+1],f=4*a,d=this._project(c,u,i[f+2],i[f+3]);d&&this._renderSegment(c,u,d[0],d[1],t)}return e&&e.value()}renderBounds(t){const e=null==t?t=new Gs:void 0;return t.rect(this.xmin,this.ymin,this.xmax-this.xmin,this.ymax-this.ymin),e&&e.value()}renderCell(t,e){const n=null==e?e=new Gs:void 0,r=this._clip(t);if(null===r||!r.length)return;e.moveTo(r[0],r[1]);let s=r.length;for(;r[0]===r[s-2]&&r[1]===r[s-1]&&s>1;)s-=2;for(let t=2;t<s;t+=2)r[t]===r[t-2]&&r[t+1]===r[t-1]||e.lineTo(r[t],r[t+1]);return e.closePath(),n&&n.value()}*cellPolygons(){const{delaunay:{points:t}}=this;for(let e=0,n=t.length/2;e<n;++e){const t=this.cellPolygon(e);t&&(t.index=e,yield t)}}cellPolygon(t){const e=new Js;return this.renderCell(t,e),e.value()}_renderSegment(t,e,n,r,s){let o;const i=this._regioncode(t,e),a=this._regioncode(n,r);0===i&&0===a?(s.moveTo(t,e),s.lineTo(n,r)):(o=this._clipSegment(t,e,n,r,i,a))&&(s.moveTo(o[0],o[1]),s.lineTo(o[2],o[3]))}contains(t,e,n){return(e=+e)==e&&(n=+n)==n&&this.delaunay._step(t,e,n)===t}*neighbors(t){const e=this._clip(t);if(e)for(const n of this.delaunay.neighbors(t)){const t=this._clip(n);if(t)t:for(let r=0,s=e.length;r<s;r+=2)for(let o=0,i=t.length;o<i;o+=2)if(e[r]==t[o]&&e[r+1]==t[o+1]&&e[(r+2)%s]==t[(o+i-2)%i]&&e[(r+3)%s]==t[(o+i-1)%i]){yield n;break t}}}_cell(t){const{circumcenters:e,delaunay:{inedges:n,halfedges:r,triangles:s}}=this,o=n[t];if(-1===o)return null;const i=[];let a=o;do{const n=Math.floor(a/3);if(i.push(e[2*n],e[2*n+1]),a=a%3==2?a-2:a+1,s[a]!==t)break;a=r[a]}while(a!==o&&-1!==a);return i}_clip(t){if(0===t&&1===this.delaunay.hull.length)return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];const e=this._cell(t);if(null===e)return null;const{vectors:n}=this,r=4*t;return n[r]||n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,s,o,i,a=null,l=e[n-2],c=e[n-1],u=this._regioncode(l,c),f=0;for(let d=0;d<n;d+=2)if(r=l,s=c,l=e[d],c=e[d+1],o=u,u=this._regioncode(l,c),0===o&&0===u)i=f,f=0,a?a.push(l,c):a=[l,c];else{let e,n,d,h,p;if(0===o){if(null===(e=this._clipSegment(r,s,l,c,o,u)))continue;[n,d,h,p]=e}else{if(null===(e=this._clipSegment(l,c,r,s,u,o)))continue;[h,p,n,d]=e,i=f,f=this._edgecode(n,d),i&&f&&this._edge(t,i,f,a,a.length),a?a.push(n,d):a=[n,d]}i=f,f=this._edgecode(h,p),i&&f&&this._edge(t,i,f,a,a.length),a?a.push(h,p):a=[h,p]}if(a)i=f,f=this._edgecode(a[0],a[1]),i&&f&&this._edge(t,i,f,a,a.length);else if(this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2))return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];return a}_clipSegment(t,e,n,r,s,o){for(;;){if(0===s&&0===o)return[t,e,n,r];if(s&o)return null;let i,a,l=s||o;8&l?(i=t+(n-t)*(this.ymax-e)/(r-e),a=this.ymax):4&l?(i=t+(n-t)*(this.ymin-e)/(r-e),a=this.ymin):2&l?(a=e+(r-e)*(this.xmax-t)/(n-t),i=this.xmax):(a=e+(r-e)*(this.xmin-t)/(n-t),i=this.xmin),s?(t=i,e=a,s=this._regioncode(t,e)):(n=i,r=a,o=this._regioncode(n,r))}}_clipInfinite(t,e,n,r,s,o){let i,a=Array.from(e);if((i=this._project(a[0],a[1],n,r))&&a.unshift(i[0],i[1]),(i=this._project(a[a.length-2],a[a.length-1],s,o))&&a.push(i[0],i[1]),a=this._clipFinite(t,a))for(let e,n=0,r=a.length,s=this._edgecode(a[r-2],a[r-1]);n<r;n+=2)e=s,s=this._edgecode(a[n],a[n+1]),e&&s&&(n=this._edge(t,e,s,a,n),r=a.length);else this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2)&&(a=[this.xmin,this.ymin,this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax]);return a}_edge(t,e,n,r,s){for(;e!==n;){let n,o;switch(e){case 5:e=4;continue;case 4:e=6,n=this.xmax,o=this.ymin;break;case 6:e=2;continue;case 2:e=10,n=this.xmax,o=this.ymax;break;case 10:e=8;continue;case 8:e=9,n=this.xmin,o=this.ymax;break;case 9:e=1;continue;case 1:e=5,n=this.xmin,o=this.ymin}r[s]===n&&r[s+1]===o||!this.contains(t,n,o)||(r.splice(s,0,n,o),s+=2)}if(r.length>4)for(let t=0;t<r.length;t+=2){const e=(t+2)%r.length,n=(t+4)%r.length;(r[t]===r[e]&&r[e]===r[n]||r[t+1]===r[e+1]&&r[e+1]===r[n+1])&&(r.splice(e,2),t-=2)}return s}_project(t,e,n,r){let s,o,i,a=1/0;if(r<0){if(e<=this.ymin)return null;(s=(this.ymin-e)/r)<a&&(i=this.ymin,o=t+(a=s)*n)}else if(r>0){if(e>=this.ymax)return null;(s=(this.ymax-e)/r)<a&&(i=this.ymax,o=t+(a=s)*n)}if(n>0){if(t>=this.xmax)return null;(s=(this.xmax-t)/n)<a&&(o=this.xmax,i=e+(a=s)*r)}else if(n<0){if(t<=this.xmin)return null;(s=(this.xmin-t)/n)<a&&(o=this.xmin,i=e+(a=s)*r)}return[o,i]}_edgecode(t,e){return(t===this.xmin?1:t===this.xmax?2:0)|(e===this.ymin?4:e===this.ymax?8:0)}_regioncode(t,e){return(t<this.xmin?1:t>this.xmax?2:0)|(e<this.ymin?4:e>this.ymax?8:0)}}const Ws=2*Math.PI,Vs=Math.pow;function Ys(t){return t[0]}function Ks(t){return t[1]}function Xs(t,e,n){return[t+Math.sin(t+e)*n,e+Math.cos(t-e)*n]}class Qs{static from(t,e=Ys,n=Ks,r){return new Qs("length"in t?function(t,e,n,r){const s=t.length,o=new Float64Array(2*s);for(let i=0;i<s;++i){const 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Array(3).concat("d8b365f5f5f55ab4ac","a6611adfc27d80cdc1018571","a6611adfc27df5f5f580cdc1018571","8c510ad8b365f6e8c3c7eae55ab4ac01665e","8c510ad8b365f6e8c3f5f5f5c7eae55ab4ac01665e","8c510abf812ddfc27df6e8c3c7eae580cdc135978f01665e","8c510abf812ddfc27df6e8c3f5f5f5c7eae580cdc135978f01665e","5430058c510abf812ddfc27df6e8c3c7eae580cdc135978f01665e003c30","5430058c510abf812ddfc27df6e8c3f5f5f5c7eae580cdc135978f01665e003c30").map(rp.Z);const mp=hp(pp);var gp=new Array(3).concat("af8dc3f7f7f77fbf7b","7b3294c2a5cfa6dba0008837","7b3294c2a5cff7f7f7a6dba0008837","762a83af8dc3e7d4e8d9f0d37fbf7b1b7837","762a83af8dc3e7d4e8f7f7f7d9f0d37fbf7b1b7837","762a839970abc2a5cfe7d4e8d9f0d3a6dba05aae611b7837","762a839970abc2a5cfe7d4e8f7f7f7d9f0d3a6dba05aae611b7837","40004b762a839970abc2a5cfe7d4e8d9f0d3a6dba05aae611b783700441b","40004b762a839970abc2a5cfe7d4e8f7f7f7d9f0d3a6dba05aae611b783700441b").map(rp.Z);const yp=hp(gp);var bp=new Array(3).concat("e9a3c9f7f7f7a1d76a","d01c8bf1b6dab8e1864dac26","d01c8bf1b6daf7f7f7b8e1864dac26","c51b7de9a3c9fde0efe6f5d0a1d76a4d9221","c51b7de9a3c9fde0eff7f7f7e6f5d0a1d76a4d9221","c51b7dde77aef1b6dafde0efe6f5d0b8e1867fbc414d9221","c51b7dde77aef1b6dafde0eff7f7f7e6f5d0b8e1867fbc414d9221","8e0152c51b7dde77aef1b6dafde0efe6f5d0b8e1867fbc414d9221276419","8e0152c51b7dde77aef1b6dafde0eff7f7f7e6f5d0b8e1867fbc414d9221276419").map(rp.Z);const vp=hp(bp);var wp=new Array(3).concat("998ec3f7f7f7f1a340","5e3c99b2abd2fdb863e66101","5e3c99b2abd2f7f7f7fdb863e66101","542788998ec3d8daebfee0b6f1a340b35806","542788998ec3d8daebf7f7f7fee0b6f1a340b35806","5427888073acb2abd2d8daebfee0b6fdb863e08214b35806","5427888073acb2abd2d8daebf7f7f7fee0b6fdb863e08214b35806","2d004b5427888073acb2abd2d8daebfee0b6fdb863e08214b358067f3b08","2d004b5427888073acb2abd2d8daebf7f7f7fee0b6fdb863e08214b358067f3b08").map(rp.Z);const _p=hp(wp);var xp=new Array(3).concat("ef8a62f7f7f767a9cf","ca0020f4a58292c5de0571b0","ca0020f4a582f7f7f792c5de0571b0","b2182bef8a62fddbc7d1e5f067a9cf2166ac","b2182bef8a62fddbc7f7f7f7d1e5f067a9cf2166ac","b2182bd6604df4a582fddbc7d1e5f092c5de4393c32166ac","b2182bd6604df4a582fddbc7f7f7f7d1e5f092c5de4393c32166ac","67001fb2182bd6604df4a582fddbc7d1e5f092c5de4393c32166ac053061","67001fb2182bd6604df4a582fddbc7f7f7f7d1e5f092c5de4393c32166ac053061").map(rp.Z);const kp=hp(xp);var qp=new Array(3).concat("ef8a62ffffff999999","ca0020f4a582bababa404040","ca0020f4a582ffffffbababa404040","b2182bef8a62fddbc7e0e0e09999994d4d4d","b2182bef8a62fddbc7ffffffe0e0e09999994d4d4d","b2182bd6604df4a582fddbc7e0e0e0bababa8787874d4d4d","b2182bd6604df4a582fddbc7ffffffe0e0e0bababa8787874d4d4d","67001fb2182bd6604df4a582fddbc7e0e0e0bababa8787874d4d4d1a1a1a","67001fb2182bd6604df4a582fddbc7ffffffe0e0e0bababa8787874d4d4d1a1a1a").map(rp.Z);const Np=hp(qp);var Sp=new Array(3).concat("fc8d59ffffbf91bfdb","d7191cfdae61abd9e92c7bb6","d7191cfdae61ffffbfabd9e92c7bb6","d73027fc8d59fee090e0f3f891bfdb4575b4","d73027fc8d59fee090ffffbfe0f3f891bfdb4575b4","d73027f46d43fdae61fee090e0f3f8abd9e974add14575b4","d73027f46d43fdae61fee090ffffbfe0f3f8abd9e974add14575b4","a50026d73027f46d43fdae61fee090e0f3f8abd9e974add14575b4313695","a50026d73027f46d43fdae61fee090ffffbfe0f3f8abd9e974add14575b4313695").map(rp.Z);const Ap=hp(Sp);var Mp=new Array(3).concat("fc8d59ffffbf91cf60","d7191cfdae61a6d96a1a9641","d7191cfdae61ffffbfa6d96a1a9641","d73027fc8d59fee08bd9ef8b91cf601a9850","d73027fc8d59fee08bffffbfd9ef8b91cf601a9850","d73027f46d43fdae61fee08bd9ef8ba6d96a66bd631a9850","d73027f46d43fdae61fee08bffffbfd9ef8ba6d96a66bd631a9850","a50026d73027f46d43fdae61fee08bd9ef8ba6d96a66bd631a9850006837","a50026d73027f46d43fdae61fee08bffffbfd9ef8ba6d96a66bd631a9850006837").map(rp.Z);const Tp=hp(Mp);var Cp=new Array(3).concat("fc8d59ffffbf99d594","d7191cfdae61abdda42b83ba","d7191cfdae61ffffbfabdda42b83ba","d53e4ffc8d59fee08be6f59899d5943288bd","d53e4ffc8d59fee08bffffbfe6f59899d5943288bd","d53e4ff46d43fdae61fee08be6f598abdda466c2a53288bd","d53e4ff46d43fdae61fee08bffffbfe6f598abdda466c2a53288bd","9e0142d53e4ff46d43fdae61fee08be6f598abdda466c2a53288bd5e4fa2","9e0142d53e4ff46d43fdae61fee08bffffbfe6f598abdda466c2a53288bd5e4fa2").map(rp.Z);const jp=hp(Cp);var Ep=new Array(3).concat("e5f5f999d8c92ca25f","edf8fbb2e2e266c2a4238b45","edf8fbb2e2e266c2a42ca25f006d2c","edf8fbccece699d8c966c2a42ca25f006d2c","edf8fbccece699d8c966c2a441ae76238b45005824","f7fcfde5f5f9ccece699d8c966c2a441ae76238b45005824","f7fcfde5f5f9ccece699d8c966c2a441ae76238b45006d2c00441b").map(rp.Z);const Op=hp(Ep);var Ip=new Array(3).concat("e0ecf49ebcda8856a7","edf8fbb3cde38c96c688419d","edf8fbb3cde38c96c68856a7810f7c","edf8fbbfd3e69ebcda8c96c68856a7810f7c","edf8fbbfd3e69ebcda8c96c68c6bb188419d6e016b","f7fcfde0ecf4bfd3e69ebcda8c96c68c6bb188419d6e016b","f7fcfde0ecf4bfd3e69ebcda8c96c68c6bb188419d810f7c4d004b").map(rp.Z);const Rp=hp(Ip);var Fp=new Array(3).concat("e0f3dba8ddb543a2ca","f0f9e8bae4bc7bccc42b8cbe","f0f9e8bae4bc7bccc443a2ca0868ac","f0f9e8ccebc5a8ddb57bccc443a2ca0868ac","f0f9e8ccebc5a8ddb57bccc44eb3d32b8cbe08589e","f7fcf0e0f3dbccebc5a8ddb57bccc44eb3d32b8cbe08589e","f7fcf0e0f3dbccebc5a8ddb57bccc44eb3d32b8cbe0868ac084081").map(rp.Z);const Pp=hp(Fp);var Dp=new Array(3).concat("fee8c8fdbb84e34a33","fef0d9fdcc8afc8d59d7301f","fef0d9fdcc8afc8d59e34a33b30000","fef0d9fdd49efdbb84fc8d59e34a33b30000","fef0d9fdd49efdbb84fc8d59ef6548d7301f990000","fff7ecfee8c8fdd49efdbb84fc8d59ef6548d7301f990000","fff7ecfee8c8fdd49efdbb84fc8d59ef6548d7301fb300007f0000").map(rp.Z);const Lp=hp(Dp);var $p=new Array(3).concat("ece2f0a6bddb1c9099","f6eff7bdc9e167a9cf02818a","f6eff7bdc9e167a9cf1c9099016c59","f6eff7d0d1e6a6bddb67a9cf1c9099016c59","f6eff7d0d1e6a6bddb67a9cf3690c002818a016450","fff7fbece2f0d0d1e6a6bddb67a9cf3690c002818a016450","fff7fbece2f0d0d1e6a6bddb67a9cf3690c002818a016c59014636").map(rp.Z);const zp=hp($p);var Zp=new Array(3).concat("ece7f2a6bddb2b8cbe","f1eef6bdc9e174a9cf0570b0","f1eef6bdc9e174a9cf2b8cbe045a8d","f1eef6d0d1e6a6bddb74a9cf2b8cbe045a8d","f1eef6d0d1e6a6bddb74a9cf3690c00570b0034e7b","fff7fbece7f2d0d1e6a6bddb74a9cf3690c00570b0034e7b","fff7fbece7f2d0d1e6a6bddb74a9cf3690c00570b0045a8d023858").map(rp.Z);const Up=hp(Zp);var Bp=new Array(3).concat("e7e1efc994c7dd1c77","f1eef6d7b5d8df65b0ce1256","f1eef6d7b5d8df65b0dd1c77980043","f1eef6d4b9dac994c7df65b0dd1c77980043","f1eef6d4b9dac994c7df65b0e7298ace125691003f","f7f4f9e7e1efd4b9dac994c7df65b0e7298ace125691003f","f7f4f9e7e1efd4b9dac994c7df65b0e7298ace125698004367001f").map(rp.Z);const Gp=hp(Bp);var Jp=new Array(3).concat("fde0ddfa9fb5c51b8a","feebe2fbb4b9f768a1ae017e","feebe2fbb4b9f768a1c51b8a7a0177","feebe2fcc5c0fa9fb5f768a1c51b8a7a0177","feebe2fcc5c0fa9fb5f768a1dd3497ae017e7a0177","fff7f3fde0ddfcc5c0fa9fb5f768a1dd3497ae017e7a0177","fff7f3fde0ddfcc5c0fa9fb5f768a1dd3497ae017e7a017749006a").map(rp.Z);const Hp=hp(Jp);var Wp=new Array(3).concat("edf8b17fcdbb2c7fb8","ffffcca1dab441b6c4225ea8","ffffcca1dab441b6c42c7fb8253494","ffffccc7e9b47fcdbb41b6c42c7fb8253494","ffffccc7e9b47fcdbb41b6c41d91c0225ea80c2c84","ffffd9edf8b1c7e9b47fcdbb41b6c41d91c0225ea80c2c84","ffffd9edf8b1c7e9b47fcdbb41b6c41d91c0225ea8253494081d58").map(rp.Z);const Vp=hp(Wp);var Yp=new Array(3).concat("f7fcb9addd8e31a354","ffffccc2e69978c679238443","ffffccc2e69978c67931a354006837","ffffccd9f0a3addd8e78c67931a354006837","ffffccd9f0a3addd8e78c67941ab5d238443005a32","ffffe5f7fcb9d9f0a3addd8e78c67941ab5d238443005a32","ffffe5f7fcb9d9f0a3addd8e78c67941ab5d238443006837004529").map(rp.Z);const Kp=hp(Yp);var Xp=new Array(3).concat("fff7bcfec44fd95f0e","ffffd4fed98efe9929cc4c02","ffffd4fed98efe9929d95f0e993404","ffffd4fee391fec44ffe9929d95f0e993404","ffffd4fee391fec44ffe9929ec7014cc4c028c2d04","ffffe5fff7bcfee391fec44ffe9929ec7014cc4c028c2d04","ffffe5fff7bcfee391fec44ffe9929ec7014cc4c02993404662506").map(rp.Z);const Qp=hp(Xp);var tm=new Array(3).concat("ffeda0feb24cf03b20","ffffb2fecc5cfd8d3ce31a1c","ffffb2fecc5cfd8d3cf03b20bd0026","ffffb2fed976feb24cfd8d3cf03b20bd0026","ffffb2fed976feb24cfd8d3cfc4e2ae31a1cb10026","ffffccffeda0fed976feb24cfd8d3cfc4e2ae31a1cb10026","ffffccffeda0fed976feb24cfd8d3cfc4e2ae31a1cbd0026800026").map(rp.Z);const em=hp(tm);var nm=new Array(3).concat("deebf79ecae13182bd","eff3ffbdd7e76baed62171b5","eff3ffbdd7e76baed63182bd08519c","eff3ffc6dbef9ecae16baed63182bd08519c","eff3ffc6dbef9ecae16baed64292c62171b5084594","f7fbffdeebf7c6dbef9ecae16baed64292c62171b5084594","f7fbffdeebf7c6dbef9ecae16baed64292c62171b508519c08306b").map(rp.Z);const rm=hp(nm);var sm=new Array(3).concat("e5f5e0a1d99b31a354","edf8e9bae4b374c476238b45","edf8e9bae4b374c47631a354006d2c","edf8e9c7e9c0a1d99b74c47631a354006d2c","edf8e9c7e9c0a1d99b74c47641ab5d238b45005a32","f7fcf5e5f5e0c7e9c0a1d99b74c47641ab5d238b45005a32","f7fcf5e5f5e0c7e9c0a1d99b74c47641ab5d238b45006d2c00441b").map(rp.Z);const om=hp(sm);var im=new Array(3).concat("f0f0f0bdbdbd636363","f7f7f7cccccc969696525252","f7f7f7cccccc969696636363252525","f7f7f7d9d9d9bdbdbd969696636363252525","f7f7f7d9d9d9bdbdbd969696737373525252252525","fffffff0f0f0d9d9d9bdbdbd969696737373525252252525","fffffff0f0f0d9d9d9bdbdbd969696737373525252252525000000").map(rp.Z);const am=hp(im);var lm=new Array(3).concat("efedf5bcbddc756bb1","f2f0f7cbc9e29e9ac86a51a3","f2f0f7cbc9e29e9ac8756bb154278f","f2f0f7dadaebbcbddc9e9ac8756bb154278f","f2f0f7dadaebbcbddc9e9ac8807dba6a51a34a1486","fcfbfdefedf5dadaebbcbddc9e9ac8807dba6a51a34a1486","fcfbfdefedf5dadaebbcbddc9e9ac8807dba6a51a354278f3f007d").map(rp.Z);const cm=hp(lm);var um=new Array(3).concat("fee0d2fc9272de2d26","fee5d9fcae91fb6a4acb181d","fee5d9fcae91fb6a4ade2d26a50f15","fee5d9fcbba1fc9272fb6a4ade2d26a50f15","fee5d9fcbba1fc9272fb6a4aef3b2ccb181d99000d","fff5f0fee0d2fcbba1fc9272fb6a4aef3b2ccb181d99000d","fff5f0fee0d2fcbba1fc9272fb6a4aef3b2ccb181da50f1567000d").map(rp.Z);const fm=hp(um);var dm=new Array(3).concat("fee6cefdae6be6550d","feeddefdbe85fd8d3cd94701","feeddefdbe85fd8d3ce6550da63603","feeddefdd0a2fdae6bfd8d3ce6550da63603","feeddefdd0a2fdae6bfd8d3cf16913d948018c2d04","fff5ebfee6cefdd0a2fdae6bfd8d3cf16913d948018c2d04","fff5ebfee6cefdd0a2fdae6bfd8d3cf16913d94801a636037f2704").map(rp.Z);const hm=hp(dm);function pm(t){return t=Math.max(0,Math.min(1,t)),"rgb("+Math.max(0,Math.min(255,Math.round(-4.54-t*(35.34-t*(2381.73-t*(6402.7-t*(7024.72-2710.57*t)))))))+", "+Math.max(0,Math.min(255,Math.round(32.49+t*(170.73+t*(52.82-t*(131.46-t*(176.58-67.37*t)))))))+", 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p}(r,l),t={genes:e};n.send(t)}catch(e){n.send({status:"error",error:e.message||e})}}},request:{typeId:"GdcTopMutatedGeneRequest"},response:{typeId:"GdcTopMutatedGeneResponse"}}}};const c={query:"\nquery GenesTable_relayQuery(\n  $genesTable_filters: FiltersArgument\n  $genesTable_size: Int\n  $genesTable_offset: Int\n  $score: String\n  $ssmCase: FiltersArgument\n  $geneCaseFilter: FiltersArgument\n  $ssmTested: FiltersArgument\n  $cnvTested: FiltersArgument\n  $cnvGainFilters: FiltersArgument\n  $cnvLossFilters: FiltersArgument\n) {\n  genesTableViewer: viewer {\n    explore {\n      cases {\n        hits(first: 0, filters: $ssmTested) {\n          total\n        }\n      }\n      filteredCases: cases {\n        hits(first: 0, filters: $geneCaseFilter) {\n          total\n        }\n      }\n      cnvCases: cases {\n        hits(first: 0, filters: $cnvTested) {\n          total\n        }\n      }\n      genes {\n        hits(first: $genesTable_size, offset: $genesTable_offset, filters: $genesTable_filters, score: $score) {\n          total\n          edges {\n            node {\n              id\n              numCases: score\n              symbol\n              name\n              cytoband\n              biotype\n              gene_id\n              is_cancer_gene_census\n              ssm_case: case {\n                hits(first: 0, filters: $ssmCase) {\n                  total\n                }\n              }\n              cnv_case: case {\n                hits(first: 0, filters: $cnvTested) {\n                  total\n                }\n              }\n              case_cnv_gain: case {\n                hits(first: 0, filters: $cnvGainFilters) {\n                  total\n                }\n              }\n              case_cnv_loss: case {\n                hits(first: 0, filters: $cnvLossFilters) {\n                  total\n                }\n              }\n            }\n          }\n        }\n      }\n    }\n  }\n}\n",getVariables:e=>{const t={genesTable_filters:{op:"and",content:[]},genesTable_size:e.maxGenes||50,genesTable_offset:0,score:"case.project.project_id",ssmCase:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}},{op:"NOT",content:{field:"genes.case.ssm.observation.observation_id",value:"MISSING"}}]},geneCaseFilter:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},ssmTested:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},cnvTested:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"}]},cnvGainFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Gain"]},op:"in"}]},cnvLossFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Loss"]},op:"in"}]}};return e.filter0&&(t.genesTable_filters.content.push(JSON.parse(JSON.stringify(e.filter0))),t.geneCaseFilter.content.push(JSON.parse(JSON.stringify(e.filter0))),t.cnvTested.content.push(JSON.parse(JSON.stringify(e.filter0))),t.cnvGainFilters.content.push(JSON.parse(JSON.stringify(e.filter0))),t.cnvLossFilters.content.push(JSON.parse(JSON.stringify(e.filter0)))),"CGC"==e.geneFilter&&(t.genesTable_filters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),t.geneCaseFilter.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),t.cnvTested.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),t.cnvGainFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),t.cnvLossFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"})),t}},f={query:"\n          query GenesTable(\n            $caseFilters: FiltersArgument\n            $genesTable_filters: FiltersArgument\n            $genesTable_size: Int\n            $genesTable_offset: Int\n            $score: String\n            $ssmCase: FiltersArgument\n            $geneCaseFilter: FiltersArgument\n            $ssmTested: FiltersArgument\n            $cnvTested: FiltersArgument\n            $cnvGainFilters: FiltersArgument\n            $cnvLossFilters: FiltersArgument\n            $sort: [Sort]\n          ) {\n            genesTableViewer: viewer {\n              explore {\n                cases {\n                  hits(first: 0, case_filters: $ssmTested) {\n                    total\n                  }\n                }\n                filteredCases: cases {\n                  hits(first: 0, case_filters: $geneCaseFilter) {\n                    total\n                  }\n                }\n                cnvCases: cases {\n                  hits(first: 0, case_filters: $cnvTested) {\n                    total\n                  }\n                }\n                genes {\n                  hits(\n                    first: $genesTable_size\n                    offset: $genesTable_offset\n                    filters: $genesTable_filters\n                    case_filters: $caseFilters\n                    score: $score\n                    sort: $sort\n                  ) {\n                    total\n                    edges {\n                      node {\n                        id\n                        numCases: score\n                        symbol\n                        name\n                        cytoband\n                        biotype\n                        gene_id\n                        is_cancer_gene_census\n                        ssm_case: case {\n                          hits(first: 0, filters: $ssmCase) {\n                            total\n                          }\n                        }\n                        cnv_case: case {\n                          hits(first: 0, filters: $cnvTested) {\n                            total\n                          }\n                        }\n                        case_cnv_gain: case {\n                          hits(first: 0, filters: $cnvGainFilters) {\n                            total\n                          }\n                        }\n                        case_cnv_loss: case {\n                          hits(first: 0, filters: $cnvLossFilters) {\n                            total\n                          }\n                        }\n                      }\n                    }\n                  }\n                }\n              }\n            }\n          }",getVariables:e=>{const t={caseFilters:{op:"and",content:[]},genesTable_filters:{op:"and",content:[]},genesTable_size:e.maxGenes||50,genesTable_offset:0,score:"case.project.project_id",ssmCase:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}},{op:"NOT",content:{field:"genes.case.ssm.observation.observation_id",value:"MISSING"}}]},geneCaseFilter:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},ssmTested:{content:[{content:{field:"cases.available_variation_data",value:["ssm"]},op:"in"}],op:"and"},cnvTested:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"}]},cnvGainFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Gain"]},op:"in"}]},cnvLossFilters:{op:"and",content:[{content:{field:"cases.available_variation_data",value:["cnv"]},op:"in"},{content:{field:"cnvs.cnv_change",value:["Loss"]},op:"in"}]}};return e.filter0&&(t.caseFilters.content.push(JSON.parse(JSON.stringify(e.filter0))),t.geneCaseFilter.content.push(JSON.parse(JSON.stringify(e.filter0))),t.cnvLossFilters.content.push(JSON.parse(JSON.stringify(e.filter0))),t.cnvGainFilters.content.push(JSON.parse(JSON.stringify(e.filter0))),t.cnvTested.content.push(JSON.parse(JSON.stringify(e.filter0)))),"CGC"==e.geneFilter&&(t.genesTable_filters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),t.cnvLossFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"}),t.cnvGainFilters.content.push({content:{field:"genes.is_cancer_gene_census",value:["true"]},op:"in"})),t}}},3202:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>o});var s=n(4065);function r({genomes:e}){return(t,n)=>{try{t.query;const r=e[t.query.genome];if(!r)throw"invalid genome name";const o=(0,s.S)(r,t.query);n.send(o)}catch(e){n.send({error:e.message||e}),e.stack&&console.log(e.stack)}}}const o={endpoint:"genelookup",methods:{get:{init:r,request:{typeId:"GeneLookupRequest"},response:{typeId:"GeneLookupResponse"},examples:[{request:{body:{input:"kr",genome:"hg38-test"}},response:{header:{status:200},body:{hits:["KRAS"]}}}]},post:{alternativeFor:"get",init:r}}}},1746:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>r});var s=n(2062);const r={endpoint:"healthcheck",methods:{get:{init:({genomes:e})=>async(t,n)=>{try{const t=await(0,s.W)(e);n.send(t)}catch(e){n.send({status:"error",error:e.message||e})}},request:{typeId:null},response:{typeId:"HealthCheckResponse"}}}}},3932:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>c});var s=n(3345),r=n(2081),o=n(4521),i=n.n(o),a=n(334),l=n.n(a);const c={endpoint:"hicdata",methods:{get:{init:f,request:{typeId:"HicdataRequest"},response:{typeId:"HicdataResponse"}},post:{alternativeFor:"get",init:f}}};function f(){return async(e,t)=>{try{const n=await function(e){return new Promise(((t,n)=>{const[o,a,c]=(0,s.ZX)({query:e});o&&n({error:"illegal file name"});const f=["log(oe)"==e.matrixType?"oe":e.matrixType?e.matrixType:"observed",e.nmeth||"NONE",a,e.pos1,e.pos2,e.isfrag?"FRAG":"BP",e.resolution],u=(0,r.spawn)(l().hicstraw,f),d=i().createInterface({input:u.stdout}),p=[],m=[];let h=0,g=0;d.on("line",(t=>{const n=t.split("\t");if(3!=n.length)return void h++;const s=Number.parseInt(n[0]),r=Number.parseInt(n[1]),o="log(oe)"==e.matrixType?Math.log(Number.parseFloat(n[2])):Number.parseFloat(n[2]);Number.isNaN(s)||Number.isNaN(r)||Number.isNaN(o)?g++:null!=e.mincutoff&&o<=e.mincutoff||p.push([s,r,o])})),u.stderr.on("data",(e=>m.push(e))),u.on("close",(()=>{const e=m.join("");e&&n({error:e}),h&&n({error:h+" lines have other than 3 fields"}),g&&n({error:g+" lines have non-numerical values in any of the 3 fields"}),t({items:p})}))}))}(e.query);t.send(n)}catch(e){t.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}},6310:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>f});var s=n(3345),r=n(7147),o=n.n(r),i=n(6464),a=n.n(i),l=n(6452),c=n.n(l);const f={endpoint:"hicstat",methods:{get:{init:u,request:{typeId:"HicstatRequest"},response:{typeId:"HicstatResponse"},examples:[{request:{body:{genome:"hg19",file:"proteinpaint_demo/hg19/hic/hic_demo.hic",embedder:"localhost"}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:u}}};function u(){return async(e,t)=>{try{const[n,r,i]=(0,s.ZX)(e);if(n)throw"illegal file name";i||await(0,s.Ic)(r);const l=await async function(e,t){const n={},s=t?await S(e,0,32e3):await N(e,0,32e3),r=new DataView(s);let i=0;if("HIC"!==A())throw Error("Unsupported hic file");const l=C();if(7!==l&&8!==l&&9!=l)throw Error("Unsupported hic version: "+l);n.version=l;const f=Number(j());let u=[];const d=1e5;if(8==l||7==l){let t=await q(e,f,d);const n=t.getInt32(0,!0);n>0&&(t=await q(e,f+n+4,d),u=await x(t,f+n+4))}const p=A();if(n["Genome ID"]=p,9==l){const t=Number(j()),n=Number(j());if(t>0&&n>0){const s=await q(e,t,n);u=await x(s,0)}}const m={},h=C();let g=0;for(;g!==h;)m[A()]=A(),g++;n.Chromosomes={},n.chrorder=[];const y=C();let b=0;for(;b!==y;){const e=A();n.chrorder.push(e),n.Chromosomes[e]=7==l||8==l?C():j(),b++}n["Base pair-delimited resolutions"]=[];const v=C();let w=0;for(;w!==v;){const e=C();n["Base pair-delimited resolutions"].push(e),w++}n["Fragment-delimited resolutions"]=[];const _=C();let k=0;for(;k!==_;){const e=C();n["Fragment-delimited resolutions"].push(e),k++}return BigInt.prototype.toJSON||Object.defineProperty(BigInt.prototype,"toJSON",{get(){return()=>String(this)}}),n.normalization=u,n;async function q(e,n,s){const r=t?await S(e,n,s):await N(e,n,s);return new DataView(r)}async function x(t,n){const s=Date.now();let r=[];const o=t.getInt32(0,!0);let i=4;for(let e=1;e<=o;e++){let e=await u("string");r.push(e),8==l||7==l?(e=await u("string"),c(4),c(8*await u("int32")),c(12*await u("int32"))):9==l&&(i+=4,e=await u("string"),i+=20)}r=[...new Set(r)];const a=Date.now()-s;return console.log(`Read normalization on ${e} on ${a/1e3} seconds`),r;async function c(e){i+e>d&&f(),i+=e}async function f(){t=await q(e,n+i,d),n+=i,i=0}async function u(e){let n;if("string"==e){let e,s="";for(;i<t.byteLength&&0!=(e=t.getUint8(i++));)i>d&&await f(),s+=String.fromCharCode(e);n=s}else{if("int32"!=e)throw"No value assigned [server/src/hicstat.ts getViewValue()]";if(i<0)return;i+4>t.byteLength&&await f(),n=t.getInt32(i,!0),i+=4}return n}}async function N(e,t,n){const s=a().promisify(o().open),r=a().promisify(o().read),i=Buffer.alloc(n),l=await s(e,"r"),c=await r(l,i,0,n,t);o().close(l,(function(e){return e}));const f=c.buffer;return f.buffer.slice(f.byteOffset,f.byteOffset+f.byteLength)}async function S(e,t,n){try{const s=t+"-"+(t+n-1);return(await c()(e,{headers:{Range:"bytes="+s}}).buffer()).buffer}catch(e){throw console.log(e.response),"error reading file, check file details"}}function A(){let e,t="";for(;0!=(e=r.getUint8(i++));)t+=String.fromCharCode(e);return t}function C(){const e=r.getInt32(i,!0);return i+=4,e}function j(){const e=r.getBigInt64(i,!0);return i+=8,e}}(r,i);t.send({out:l})}catch(e){t.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}},5852:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>o});var s=n(938),r=n(2974);const o={endpoint:"termdb/categories",methods:{get:{init:i,request:{typeId:"getcategoriesRequest"},response:{typeId:"getcategoriesResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",getcategories:1,tid:"diaggrp",term1_q:{isAtomic:!0,hiddenValues:{},type:"values",groupsetting:{disabled:!0},mode:"discrete"},filter:{type:"tvslst",in:!0,join:"",lst:[{tag:"cohortFilter",type:"tvs",tvs:{term:{name:"Cohort",type:"categorical",values:{ABC:{label:"ABC"},XYZ:{label:"XYZ"}},id:"subcohort",isleaf:!1,groupsetting:{disabled:!0}},values:[{key:"ABC",label:"ABC"}]}}]}}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:i}}};function i({genomes:e}){return async(t,n)=>{const o=t.query;try{const i=e[t.query.genome];if(!i)throw"invalid genome name";const l=i.datasets[t.query.dslabel];if(!l)throw"invalid dataset name";const c=l.cohort.termdb;if(!c)throw"invalid termdb object";await async function(e,t,n,o,i){if(!e.tid)throw".tid missing";const l="geneVariant"==e.type?{name:e.tid,type:"geneVariant",isleaf:!0}:n.q.termjsonByOneid(e.tid),c={filter:e.filter,terms:"geneVariant"==e.type?[{term:l,q:{isAtomic:!0}}]:[{id:e.tid,term:l,q:e.term1_q||a(l,e)}],currentGeneNames:e.currentGeneNames,rglst:e.rglst},f=await(0,r.Yu)(c,o,i);if(f.error)throw f.error;const u=[];if("geneVariant"==e.type){const t=f.samples,n=new Map;if(o.assayAvailability?.byDt)for(const[e,t]of Object.entries(o.assayAvailability.byDt))t.byOrigin&&n.set(parseInt(e),{byOrigin:{germline:{},somatic:{}}});const s=new Set;for(const[r,o]of Object.entries(t)){const t=o[e.tid].values;s.clear();for(const e of t){n.has(e.dt)||n.set(e.dt,{});const t=n.get(e.dt);t.byOrigin?(t.byOrigin[e.origin][e.class]||(t.byOrigin[e.origin][e.class]=1,s.add(`${e.dt} ${e.origin} ${e.class}`)),s.has(`${e.dt} ${e.origin} ${e.class}`)||(s.add(`${e.dt} ${e.origin} ${e.class}`),t.byOrigin[e.origin][e.class]+=1)):(t[e.class]||(s.add(`${e.dt} ${e.class}`),t[e.class]=1),s.has(`${e.dt} ${e.class}`)||(s.add(`${e.dt} ${e.class}`),t[e.class]+=1))}}for(const[e,t]of n)u.push({dt:e,classes:t})}else{const t=new Map;for(const n in f.samples){const s=f.samples[n][e.tid];s&&("key"in s&&t.set(s.key,1+(t.get(s.key)||0)))}for(const[n,s]of t)u.push({samplecount:s,key:n,label:f.refs?.byTermId?.[e.tid]?.events?.find((e=>e.event===n)).label||l?.values?.[n]?.label||n})}const d=(0,s.Tt)(l,f.refs?.byTermId?.[e.tid]?.bins||[],f.refs?.byTermId?.[e.tid]?.events,e.term1_q);d.length&&u.sort(((e,t)=>d.indexOf(e.label)-d.indexOf(t.label)));t.send({lst:u,orderedLabels:d})}(o,n,c,l,i)}catch(e){n.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}function a(e,t){if("categorical"==e.type)return{};if("survival"==e.type)return{};if("integer"==e.type||"float"==e.type)return e.bins.default;if("condition"==e.type)return{mode:t.mode,breaks:t.breaks,bar_by_grade:t.bar_by_grade,bar_by_children:t.bar_by_children,value_by_max_grade:t.value_by_max_grade,value_by_most_recent:t.value_by_most_recent,value_by_computable_grade:t.value_by_computable_grade};if("geneVariant"==e.type)return{};throw"unknown term type"}},4924:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>m,validate_query_geneExpression:()=>g});var s=n(1017),r=n.n(s),o=n(7147),i=n.n(o),a=n(9157),l=n(3345),c=n(334),f=n.n(c),u=n(1169),d=n(901),p=n(2273);const m={endpoint:"termdb/cluster",methods:{all:{init:function({genomes:e}){return async(t,n)=>{const s=t.query;let o;try{const t=e[s.genome];if(!t)throw"invalid genome name";const n=t.datasets[s.dslabel];if(!n)throw"invalid dataset name";if(n.__gdc&&!n.__gdc.doneCaching)throw"The server has not finished caching the case IDs: try again in ~2 minutes";if(s.dataType!=p.dtgeneexpression)throw"unknown q.dataType "+s.dataType;if(!n.queries?.geneExpression)throw"no geneExpression data on this dataset";o=await async function(e,t){const{gene2sample2value:n,byTermId:s,bySampleId:o}=await t.queries.geneExpression.get(e);if(0==n.size)throw"no data";if(1==n.size){const e=Array.from(n.keys())[0];return{gene:e,data:n.get(e)}}const c=Date.now(),u=await async function(e,t){const n=new Set;for(const t of e.values()){for(const e in t)n.add(e);break}const s={matrix:[],row_names:[],col_names:[...n],cluster_method:t.clusterMethod,plot_image:!1};for(const[t,n]of e){s.row_names.push(t);const e=[];for(const t of s.col_names)e.push(n[t]||0);s.matrix.push(h(e))}const o=r().join(f().cachedir,Math.random().toString()+".json");await l.Sf(o,JSON.stringify(s));const c=JSON.parse(await(0,a.default)(r().join(f().binpath,"utils/hclust.R"),[],[o]));await i().promises.unlink(o);const u=c.RowOrder.map((e=>s.row_names.indexOf(e.name))),d=c.ColOrder.map((e=>s.col_names.indexOf(e.name))),p=[];for(const e of u){const t=[];for(const n of d)t.push(s.matrix[e][n]);p.push(t)}return{row:{merge:c.RowMerge,height:c.RowHeight,order:c.RowOrder,inputOrder:s.row_names},col:{merge:c.ColumnMerge,height:c.ColumnHeight,order:c.ColOrder,inputOrder:s.col_names},matrix:p}}(n,e);f().debugmode&&console.log("clustering done:",Date.now()-c,"ms");return{clustering:u,byTermId:s,bySampleId:o}}(s,n)}catch(e){e.stack&&console.log(e.stack),o={status:e.status||400,error:e.message||e}}n.send(o)}},request:{typeId:"TermdbClusterRequest"},response:{typeId:"TermdbClusterResponse"}}}};function h(e){const t=e.reduce(((e,t)=>e+t),0)/e.length,n=Math.sqrt(e.reduce(((e,n)=>e+Math.pow(n-t,2)),0)/e.length);return 0==n?e:e.map((e=>(e-t)/n))}async function g(e,t){const n=e.queries.geneExpression;if(n)if("gdcapi"!=n.src){if("native"!=n.src)throw"unknown queries.geneExpression.src";await async function(e,t,n){e.file.startsWith(f().tpmasterdir)||(e.file=r().join(f().tpmasterdir,e.file));e.samples||(e.samples=[]);await l.LC(e.file),e.nochr=await l.Jy(e.file,null,n),e.samples=[];{const n=await l.ZD(e.file);if(!n[0])throw"header line missing from "+e.file;const s=n[0].split("\t");if("#chr\tstart\tstop\tgene"!=s.slice(0,4).join("\t"))throw"header line has wrong content for columns 1-4";for(let n=4;n<s.length;n++){const r=t.cohort.termdb.q.sampleName2id(s[n]);if(null==r)throw"queries.geneExpression: unknown sample from header: "+s[n];e.samples.push(r)}console.log(e.samples.length,"samples from geneExpression of",t.label)}e.get=async s=>{const r=await(0,d.T)(s,e.samples,t);if(0==r?.size)return{gene2sample2value:new Set,byTermId:{},bySampleId:{}};const o={},i=e.samples||[];if(r)for(const e of r)o[e]={label:t.cohort.termdb.q.id2sampleName(e)};else for(const e of i)o[e]={label:t.cohort.termdb.q.id2sampleName(e)};const a=new Map;for(const t of s.genes){if(!t.gene)continue;if(!t.chr){const e=n.genedb.getjsonbyname.all(t.gene);if(0==e.length)continue;const s=JSON.parse(e.find((e=>e.isdefault)).genemodel||e[0].genemodel);t.start=s.start,t.stop=s.stop,t.chr=s.chr}const s={};await l.UE({args:[e.file,(e.nochr?t.chr?.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],callback:e=>{const n=e.split("\t");if(n[3].toLowerCase()==t.gene.toLowerCase())for(let e=4;e<n.length;e++){const t=i[e-4];if(r&&!r.has(t))continue;if(!n[e])continue;const o=Number(n[e]);if(Number.isNaN(o))throw"exp value not number";s[t]=o}}}),Object.keys(s).length&&a.set(t.gene,s)}return{gene2sample2value:a,byTermId:{},bySampleId:o}}}(n,e,t)}else(0,u.eG)(e,t)}},2262:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>o});var s=n(8907),r=n(8615);const o={endpoint:"termdb/descrstats",methods:{all:{init:function({genomes:e}){return async(t,n)=>{const o=t.query;try{const i=e[t.query.genome];if(!i)throw"invalid genome name";const a=i.datasets[t.query.dslabel];if(!a)throw"invalid 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o={ds:r,term_id:e.tid,filter:e.filter},i=await s.tt(o);t.send({lst:i})}(r,n,a,i)}catch(e){n.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}},2630:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>o});var s=n(8907),r=n(7027);const o={endpoint:"termdb/getpercentile",methods:{get:{init:i,request:{typeId:"getpercentileRequest"},response:{typeId:"getpercentileResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",getpercentile:[50],tid:"agedx",filter:{type:"tvslst",in:!0,join:"",lst:[{tag:"cohortFilter",type:"tvs",tvs:{term:{name:"Cohort",type:"categorical",values:{ABC:{label:"ABC"},XYZ:{label:"XYZ"}},id:"subcohort",isleaf:!1,groupsetting:{disabled:!0}},values:[{key:"ABC",label:"ABC"}]}}]}}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:i}}};function i({genomes:e}){return async(t,n)=>{const o=t.query;try{const i=e[t.query.genome];if(!i)throw"invalid genome name";const 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r={endpoint:"termdb/rootterm",methods:{get:{init:o,request:{typeId:"getroottermRequest"},response:{typeId:"getroottermResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",default_rootterm:1,cohortValues:"ABC"}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:o}}};function o({genomes:e}){return async(t,n)=>{const r=t.query;r.cohortValues&&r.cohortValues,r.treeFilter&&r.treeFilter;try{const o=e[t.query.genome];if(!o)throw"invalid genome name";const[i,a]=(0,s.pq)(o,r);if(!i)throw"invalid dataset name";if(!a)throw"invalid termdb object";await async function(e,t,n){const s=e.cohortValues?e.cohortValues:"",r=e.treeFilter?e.treeFilter:"";t.send({lst:await n.q.getRootTerms(s,r)})}(r,n,a)}catch(e){n.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}},3967:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>r});var s=n(2826);const r={endpoint:"termdb/termchildren",methods:{get:{init:o,request:{typeId:"gettermchildrenRequest"},response:{typeId:"gettermchildrenResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",get_children:1,cohortValues:"ABC",tid:"GO:0000001"}},response:{header:{status:200}}}]},post:{alternativeFor:"get",init:o}}};function o({genomes:e}){return async(t,n)=>{const r=t.query;try{const o=e[t.query.genome];if(!o)throw"invalid genome name";const[i,a]=await(0,s.pq)(o,r);if(!i)throw"invalid dataset name";if(!a)throw"invalid termdb object";await async function(e,t,n){if(!e.tid)throw"no parent term id";const r=e.cohortValues?e.cohortValues:"",o=e.treeFilter?e.treeFilter:"",i=await n.q.getTermChildren(e.tid,r,o);t.send({lst:i.map(s.iK)})}(r,n,a)}catch(e){n.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}},3677:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>u,validate_query_singleSampleMutation:()=>d});var s=n(7147),r=n.n(s),o=n(1017),i=n.n(o),a=n(3345),l=n(334),c=n.n(l),f=n(1169);const u={endpoint:"termdb/singleSampleMutation",methods:{get:{init:function({genomes:e}){return async(t,n)=>{const s=t.query;let r;try{const t=e[s.genome];if(!t)throw"invalid genome name";const n=t.datasets[s.dslabel];if(!n)throw"invalid dataset name";if(!n.queries?.singleSampleMutation)throw"not supported on this dataset";r=await n.queries.singleSampleMutation.get(s)}catch(e){e.stack&&console.log(e.stack),r={status:e.status||400,error:e.message||e}}n.send(r)}},request:{typeId:"TermdbSingleSampleMutationRequest"},response:{typeId:"TermdbSingleSampleMutationResponse"}}}};async function d(e,t){const n=e.queries.singleSampleMutation;if(n)if("gdcapi"==n.src)(0,f.sV)(e,t);else{if("native"!=n.src)throw"unknown singleSampleMutation.src";n.get=async t=>{let s=t.sample;if(e.cohort?.termdb?.q?.sampleName2id&&(s=e.cohort.termdb.q.sampleName2id(t.sample),null==s))return[];const 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of n)e&&(e.total=e.sum/e.count,delete e.sum,delete e.count);return n}async function fn(e,t){for(const e of t.regions)e.lines.length>0&&e.ntwidth>=Dt&&(e.to_checkmismatch=!0,e.referenceseq=await hn(t.genome,e.chr+":"+(e.start+1)+"-"+e.stop));for(const n of e)for(const e of n.segments){const n=t.regions[e.ridx];if(!n.to_checkmismatch)continue;const s=[];for(const t of e.boxes)null!=t.cidx&&"M"==t.opr&&(t.s=e.seq.substr(t.cidx,t.len),vn(s,n,t,t.s));s.length&&e.boxes.push(...s)}for(const e of t.regions)delete e.to_checkmismatch,delete e.referenceseq}function un(e,t){if(!e.asPaired){const n=[];for(let s=0;s<e.regions.length;s++){const r=e.regions[s];for(const o of t.templates){o.ridx=s;const t=dn(o,r,e);t&&n.push({x1:t.x1,x2:t.x2,__tempscore:t.tempscore,segments:[t]})}}return n}const n=new Map;for(let s=0;s<e.regions.length;s++){const r=e.regions[s];for(const o of t.templates){o.ridx=s;const t=dn(o,r,e);if(!t||!t.qname)continue;const 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n={opr:o,start:e,len:a,cidx:r-a};0==w.boxes.length?(n.start-=a,(i||Math.max(e,t.start)<=Math.min(e+a-1,t.stop))&&w.boxes.push(n)):w.boxes.push(n)}else{if(i||Math.max(e,t.start)<Math.min(e+a-1,t.stop)){const t={opr:o,start:e,len:a,cidx:r-a};w.boxes.push(t)}e+=a}else(e>=t.start&&e<=t.stop||e+a-1>=t.start&&e+a-1<=t.stop||i)&&w.boxes.push({opr:o,start:e,len:a}),e+=a;else(i||e>t.start&&e<t.stop)&&a*t.ntwidth>=Rt&&w.boxes.push({opr:"I",start:e,len:a,cidx:r-a});else(i||Math.max(e,t.start)<=Math.min(e+a-1,t.stop))&&w.boxes.push({opr:o,start:e,len:a,cidx:r-a}),e+=a;else{const l={opr:o,start:e,len:a,cidx:r-a};0==w.boxes.length?(l.start-=a,l.cidx=0,(i||Math.max(e,t.start)<=Math.min(e+a-1,t.stop))&&w.boxes.push(l)):w.boxes.push(l),s=n+1}}if(0==w.boxes.length)return void(n&&n.readcount_skipped++);w.segstop=e,w.x1=t.x+t.scale(w.boxes[0].start),w.x2=t.x+t.scale((_=w.boxes,Math.max(..._.map((e=>e.start+e.len)))))}var _;return w}async function pn(e,t,n){const[s,r]=function(e,t){let n=(t.groups.length>1?Vt/2:Vt)/e;return n>10?[Math.min(15,Math.floor(n)),1]:n>7?[Math.floor(n),1]:n>3?[Math.ceil(n),0]:n>1?[Math.floor(n),0]:[n,0]}(e.stacks.length,t);e.stackheight=s,e.stackspace=r;for(const t of e.regions)t.to_printnt=e.stackheight>7&&t.ntwidth>=7,t.to_qual=t.ntwidth>=Ft;if(e.stacks.length&&(e.stackheight>=Kt&&n.length<Zt?e.returntemplatebox=[]:e.partstack||(e.allowpartstack=!0)),e.stackheight>=Lt){let t=0;for(const e of n)for(const n of e.segments)t=Math.max(t,n.x2-n.x1);t>.7*e.stackheight&&(e.canClipArrowhead=!0)}}function mn(e,t,n){if(t.asPaired){e.stacks=[];const s=[],r=[];for(const e of n){let n=e.segments[0].ridx;1==e.segments.length||2==e.segments.length&&e.segments[0].ridx==e.segments[1].ridx?(e.x1=Math.max(t.regions[n].x,e.x1),e.x2=Math.min(t.regions[n].x+t.regions[n].width,e.x2),s.push(e)):2==e.segments.length&&e.segments[0].ridx!=e.segments[1].ridx&&(e.x1=e.x1,e.x2=e.x2,r.push(e))}if(s.sort(((e,t)=>e.x1-t.x1)),r.sort(((e,t)=>e.x1-t.x1)),r.length>0){const e=[],t=[],o=r[0];for(const n of s)n.x1<o.x1&&n.x2<o.x1?e.push(n):t.push(n);n=[...e,...r,...t]}for(const s of n){let n=s.segments[0].ridx,r=null;if(!t.variant)for(let o=0;o<e.stacks.length;o++){if(s.x2==t.regions[n].x+t.regions[n].width&&e.stacks[o]<s.x1){r=o,e.stacks[o]=s.x2;break}if(e.stacks[o]+t.stacksegspacing<s.x1){r=o,e.stacks[o]=s.x2;break}}null==r&&(r=e.stacks.length,e.stacks[r]=s.x2),s.y=r}}else{n.sort(((e,t)=>e.x1-t.x1)),e.stacks=[];for(let s=0;s<t.regions.length;s++)for(const r of n)if(r.segments[0].ridx==s){let n=null;if(!t.variant&&!t.sv)for(let o=0;o<e.stacks.length;o++)if(e.stacks[o]+t.stacksegspacing<r.x1&&e.stacks[o]+t.stacksegspacing<t.regions[s].x+t.regions[s].width){n=o,e.stacks[o]=r.x2;break}null==n&&(n=e.stacks.length,e.stacks[n]=r.x2),r.y=n}}return n=function(e,t,n){if(!e.partstack)return t;const s=t.filter((t=>t.y>=e.partstack.start&&t.y<=e.partstack.stop));s.forEach((t=>t.y-=e.partstack.start)),t=s,e.stacks=[];for(let t=e.partstack.start;t<=e.partstack.stop;t++)e.stacks.push(0);return e.returntemplatebox=[],t}(e,n),n}async function hn(e,t){const n=(await F.Kf(e,t)).split("\n");return n.shift(),n.join("").toUpperCase()}function gn(e,t,n){const s=function(e,t,n){const s=[];for(let t=0;t<e.stacks.length;t++)s.push(e.stackheight);if(function(e,t){if(!t.asPaired)return;for(const t of e.regions)if(t.ntwidth<=$t)return;e.overlapRP_multirows=!0,e.overlapRP_hlline=e.stackspace>0}(e,n),e.overlapRP_multirows)for(const n of t)n.segments.length<=1||n.segments[0].ridx!=n.segments[1].ridx||(n.height=bn(n,e.stackheight),s[n.y]=Math.max(s[n.y],n.height));const r=[];let o=e.stackspace;for(const t of s)r.push(o),o+=t+e.stackspace;return e.canvasheight=o,r}(e,t,n);for(const n of t){n.y=s[n.y];for(const t of n.segments){const n=e.regions[t.ridx].to_qual?yn(t.qual):null;for(const e of t.boxes)null!=e.cidx&&"H"!=e.opr&&(n&&(e.qual=n.slice(e.cidx,e.cidx+e.len)),"I"==e.opr?e.s=t.seq.substr(e.cidx,e.len):"X"!=e.opr&&"S"!=e.opr||(e.s=t.seq.substr(e.cidx,e.len)),delete e.cidx);delete t.seq,delete t.qual}}}function yn(e){if("*"==e)return null;const t=[];for(let n=0;n<e.length;n++){const s=e[n].charCodeAt(0)-33;t.push(s)}return t}function bn(e,t){if(2==e.segments.length){const[n,s]=e.segments;return n.x2>s.x1?(s.shiftdownrow=1,2*t):t}console.log("more than 2 segments",e.segments.length);const n=[];for(const t of e.segments){let e=null;for(let s=0;s<n.length;s++)if(n[s]<t.x1){e=s,n[s]=t.x2;break}null==e&&(e=n.length,n[e]=t.x2),t.shiftdownrow=e}return t*n.length}function vn(e,t,n,s){for(let r=0;r<s.length;r++){if(n.start+r<t.start||n.start+r>t.stop)continue;const o=s[r];if(t.referenceseq[n.start+r-t.start]!=o.toUpperCase()){const t={opr:"X",start:n.start+r,len:1,s:o,cidx:n.cidx+r};e.push(t)}}}function wn(e,t,n,s){if(n.returntemplatebox){const e=n.regions[t.segments[0].ridx];let r;if(e.width=n.widths[t.segments[0].ridx],s.asPaired)if(2==t.segments.length)r=t.segments[0].ridx!=t.segments[1].ridx?{qname:t.segments[0].qname,x1:t.x1,x2:t.x2,y1:t.y,y2:t.y+(t.height||n.stackheight),start:Math.min(...t.segments.map((e=>e.segstart))),stop:Math.max(...t.segments.map((e=>e.segstop))),multi_region:!0}:{qname:t.segments[0].qname,x1:Math.max(e.x,t.x1),x2:Math.min(t.x2,e.width),y1:t.y,y2:t.y+(t.height||n.stackheight),start:Math.min(...t.segments.map((e=>e.segstart))),stop:Math.max(...t.segments.map((e=>e.segstop)))};else{const e=t.segments[0],s=n.regions[e.ridx];s.width=n.widths[e.ridx],r={qname:t.segments[0].qname,x1:Math.max(s.x,t.x1),x2:Math.min(t.x2,s.width),y1:t.y,y2:t.y+(t.height||n.stackheight),start:Math.min(...t.segments.map((e=>e.segstart))),stop:Math.max(...t.segments.map((e=>e.segstop)))}}else r={qname:t.segments[0].qname,x1:Math.max(e.x,t.x1),x2:Math.min(t.x2,e.x+e.width),y1:t.y,y2:t.y+(t.height||n.stackheight),start:Math.min(...t.segments.map((e=>e.segstart))),stop:Math.max(...t.segments.map((e=>e.segstop)))},t.segments[0].isfirst&&(r.isfirst=!0),t.segments[0].islast&&(r.islast=!0);n.returntemplatebox.push(r)}for(let r=0;r<t.segments.length;r++){const o=t.segments[r],i=n.regions[o.ridx];if(i.width=n.widths[o.ridx],0==r){_n(e,o,t.y,n,s);continue}const a=t.segments[r-1],l=n.regions[a.ridx];if(l.width=n.widths[a.ridx],a.x2<=o.x1||t.segments[0].ridx!=t.segments[1].ridx){_n(e,o,t.y,n,s);const r=Math.floor(t.y+n.stackheight/2)+.5;if(e.strokeStyle=n.stackheight<=2?Nt:nt,e.setLineDash([5,3]),e.beginPath(),l.x==i.x?(e.moveTo(a.x2,r),e.lineTo(o.x1,r)):l.x<a.x2&&o.x1<i.width&&(e.moveTo(Math.min(a.x2,l.width),r),e.lineTo(Math.max(o.x1,i.x),r)),e.stroke(),n.overlapRP_hlline){const s=a.boxes.reduce(((e,t)=>e.start+e.len>t.start+t.len?e:t));if(s.start+s.len==o.boxes[0].start){e.strokeStyle=St,e.setLineDash([]),e.beginPath();const s=Math.floor(o.x1)+.5;e.moveTo(s,t.y),e.lineTo(s,t.y+n.stackheight),e.stroke()}}}else if(n.overlapRP_multirows){if(_n(e,o,t.y+n.stackheight,n,s),n.overlapRP_hlline){const s=Math.floor(t.y+n.stackheight)+.5;e.strokeStyle=St,e.setLineDash([]),e.beginPath(),l.x<=a.x2&&o.x1<=i.width&&(e.moveTo(Math.max(o.x1,i.x),s),e.lineTo(Math.min(a.x2,l.width),s)),e.stroke()}}else _n(e,o,t.y,n,s)}null!=t.__tempscore&&r().features.indel_read_alignment_scores&&(e.fillStyle="blue",e.font=n.stackheight+"pt Arial",e.fillText(t.__tempscore,s.regions[0].width-100,t.y+n.stackheight/2))}function _n(e,t,n,s,r){const o=s.regions[t.ridx];o.width=s.widths[t.ridx];for(const r of t.boxes){const i=o.x+o.scale(r.start);if("P"!=r.opr&&"I"!=r.opr)if("H"!=r.opr)if("D"!=r.opr&&"N"!=r.opr)if("*"!=r.opr){if("X"!=r.opr&&"S"!=r.opr){if("M"!=r.opr&&"="!=r.opr)throw"unknown opr at rendering: "+r.opr;if(o.to_qual&&r.qual){let a=i;r.qual.forEach((r=>{t.rnext?e.fillStyle=it(r/Bt):t.discord_orientation?e.fillStyle=bt(r/Bt):t.discord_wrong_insertsize?e.fillStyle=lt(r/Bt):t.discord_unmapped2?e.fillStyle=gt(r/Bt):e.fillStyle=rt(r/Bt),a+o.ntwidth+Ut<o.width&&o.x<=a?e.fillRect(a,n,o.ntwidth+Ut,s.stackheight):a<o.width&&a+o.ntwidth+Ut>=o.width&&o.x<=a?e.fillRect(a,n,o.width-a,s.stackheight):a<=o.x&&a+o.ntwidth+Ut>o.x&&e.fillRect(o.x,n,o.ntwidth+Ut+a-o.x,s.stackheight),a+=o.ntwidth}))}else r.qual?t.rnext?e.fillStyle=ot:t.discord_orientation?e.fillStyle=yt:t.discord_wrong_insertsize?e.fillStyle=at:t.discord_unmapped2?e.fillStyle=ht:e.fillStyle=nt:o.to_printnt?e.fillStyle="white":t.rnext?e.fillStyle=ot:t.discord_orientation?e.fillStyle=yt:t.discord_wrong_insertsize?e.fillStyle=at:t.discord_unmapped2?e.fillStyle=ht:e.fillStyle=nt,i+r.len*o.ntwidth+Ut<o.width&&i<o.width&&o.x<i+Ut?e.fillRect(i,n,r.len*o.ntwidth+Ut,s.stackheight):i+r.len*o.ntwidth+Ut<o.width&&o.x>=i?e.fillRect(o.x,n,r.len*o.ntwidth+Ut+i-o.x,s.stackheight):i+r.len*o.ntwidth+Ut>=o.width&&o.x<i?e.fillRect(i,n,o.width-i,s.stackheight):i+r.len*o.ntwidth+Ut>=o.width&&o.x>=i&&e.fillRect(o.x,n,o.width-i,s.stackheight);if(o.to_printnt){e.font=Math.min(o.ntwidth,s.stackheight-2)+"pt Arial",r.qual?e.fillStyle="white":e.fillStyle="black";for(let t=0;t<r.s.length;t++)i+o.ntwidth*(t+.5)<o.width&&i<o.width&&o.x<=i+o.ntwidth*(t+.5)&&e.fillText(r.s[t],i+o.ntwidth*(t+.5),n+s.stackheight/2)}}else if(o.to_qual&&r.qual){o.to_printnt&&(e.font=Math.min(o.ntwidth,s.stackheight-2)+"pt Arial");let t=i;for(let i=0;i<r.qual.length;i++){const a=r.qual[i]/Bt;e.fillStyle="S"==r.opr?mt(a):ut(a),t+o.ntwidth+Ut<o.x+o.width&&o.x<=t?e.fillRect(t,n,o.ntwidth+Ut,s.stackheight):t<o.x+o.width&&t+o.ntwidth+Ut>=o.x+o.width&&o.x<=t?e.fillRect(t,n,o.width+o.x-t,s.stackheight):t<=o.x&&t+o.ntwidth+Ut>o.x&&e.fillRect(o.x,n,o.ntwidth+Ut+t-o.x,s.stackheight),o.to_printnt&&(r.qual?e.fillStyle="white":e.fillStyle="black",t+o.ntwidth/2<o.width&&t<o.width&&o.x<=t+o.ntwidth/2&&e.fillText(r.s[i],t+o.ntwidth/2,n+s.stackheight/2)),t+=o.ntwidth}}else if(e.fillStyle="S"==r.opr?dt:ct,i+r.len*o.ntwidth+Ut<o.width&&o.x<i?e.fillRect(i,n,r.len*o.ntwidth+Ut,s.stackheight):i+r.len*o.ntwidth+Ut<o.width&&o.x>=i?e.fillRect(o.x,n,r.len*o.ntwidth+Ut+i-o.x,s.stackheight):i+r.len*o.ntwidth+Ut<=o.width&&o.x<i&&e.fillRect(i,n,o.width-i,s.stackheight),o.to_printnt&&!r.qual){e.font=Math.min(o.ntwidth,s.stackheight-2)+"pt Arial",r.qual?e.fillStyle="white":e.fillStyle="black";for(let t=0;t<r.s.length;t++)i+o.ntwidth*(t+.5)<o.width&&i<o.width&&o.x<=i+o.ntwidth*(t+.5)&&e.fillText(r.s[t],i+o.ntwidth*(t+.5),n+s.stackheight/2)}}else{if(o.to_qual&&r.qual){let a=i;r.qual.forEach((r=>{t.discord_unmapped2&&(e.fillStyle=gt(r/Bt)),e.fillRect(a,n,o.ntwidth+Ut,s.stackheight),a+=o.ntwidth}))}else t.discord_unmapped2&&(e.fillStyle=ht),e.fillRect(i,n,r.len*o.ntwidth+Ut,s.stackheight);o.to_printnt&&(e.font=Math.min(o.ntwidth,s.stackheight-2)+"pt Arial")}else{"D"==r.opr?e.strokeStyle=xt:e.strokeStyle=s.stackheight<=2?Nt:nt,e.setLineDash([]);const t=Math.floor(n+s.stackheight/2)+.5;if(e.beginPath(),e.moveTo(Math.max(i,o.x),t),e.lineTo(Math.min(i+r.len*o.ntwidth,o.x+o.width),t),e.stroke(),s.stackheight>Pt){const t=Math.max(o.x,i),a=Math.min(o.x+o.width,i+r.len*o.ntwidth);if(a-t>=50){const i=Math.min(Gt,Math.max(zt,s.stackheight-2));e.font=i+"pt Arial";const l=e.measureText(r.len+" bp").width;l<a-t-20&&(e.fillStyle="white",(a+t)/2+l/2<o.width&&o.x<(a+t)/2-l/2?(e.fillRect((a+t)/2-l/2,n,l,s.stackheight),e.fillStyle=nt,e.fillText(r.len+" bp",(a+t)/2,n+s.stackheight/2)):(a+t)/2+l/2<o.width&&o.x>=(a+t)/2-l/2?(e.fillRect(o.x,n,l+(a+t)/2-l/2-o.x,s.stackheight),e.fillStyle=nt,e.fillText(r.len+" bp",(a+t)/2,n+s.stackheight/2)):(a+t)/2+l/2>=o.width&&o.x<(a+t)/2-l/2&&(e.fillRect((a+t)/2-l/2,n,o.width-(a+t)/2+l/2,s.stackheight),e.fillStyle=nt,e.fillText(r.len+" bp",(a+t)/2,n+s.stackheight/2)))}}}else e.fillStyle="white",i+r.len*o.ntwidth+Ut<o.width&&o.x<i?e.fillRect(i,n,r.len*o.ntwidth+Ut,s.stackheight):i+r.len*o.ntwidth+Ut<o.width&&o.x>=i?e.fillRect(o.x,n,r.len*o.ntwidth+Ut+i-o.x,s.stackheight):i+r.len*o.ntwidth+Ut<=o.width&&o.x<i&&e.fillRect(i,n,o.width-i,s.stackheight)}!function(e,t,n,s,r){if(!n.canClipArrowhead)return;if(t.x2-t.x1<5)return;if(t.forward){const o=Math.ceil(t.x2+Ut);o<=s.width+n.stackheight/2&&(e.fillStyle="white",e.beginPath(),e.moveTo(o-n.stackheight/2,r),e.lineTo(o,r),e.lineTo(o,r+n.stackheight/2),e.lineTo(o-n.stackheight/2,r),e.closePath(),e.fill(),e.beginPath(),e.moveTo(o-n.stackheight/2,r+n.stackheight),e.lineTo(o,r+n.stackheight),e.lineTo(o,r+n.stackheight/2),e.lineTo(o-n.stackheight/2,r+n.stackheight),e.closePath(),e.fill())}else{const o=t.x1;o>=s.x&&(e.fillStyle="white",e.beginPath(),e.moveTo(o+n.stackheight/2,r),e.lineTo(o,r),e.lineTo(o,r+n.stackheight/2),e.lineTo(o+n.stackheight/2,r),e.closePath(),e.fill(),e.beginPath(),e.moveTo(o+n.stackheight/2,r+n.stackheight),e.lineTo(o,r+n.stackheight),e.lineTo(o,r+n.stackheight/2),e.lineTo(o+n.stackheight/2,r+n.stackheight),e.closePath(),e.fill())}}(e,t,s,o,n),t.rnext&&(o.to_qual||t.x2-t.x1>=20&&s.stackheight>=7&&(e.font=Math.min(kt,Math.max(qt,s.stackheight-4))+"pt Arial",e.fillStyle="white",e.fillText((r.nochr?"chr":"")+t.rnext,(t.x1+t.x2)/2,n+s.stackheight/2,t.x2-t.x1)))}function kn(e,t,n,s){for(const[e,n]of t.regions.entries()){if(!n.to_printnt)continue;const t=new Set;for(const r of s)for(const s of r.segments){if(s.ridx!=e)continue;const r=s.boxes.filter((e=>"I"==e.opr));if(r.length)for(const e of r)t.add(n.x+n.scale(e.start))}}for(const n of s)for(const s of n.segments){const r=t.regions[s.ridx],o=s.boxes.filter((e=>"I"==e.opr));if(o.length){e.font=Math.max(kt,t.stackheight-2)+"pt Arial";for(const i of o){const o=r.x+r.scale(i.start);let a;i.qual?e.fillStyle=_t(i.qual.reduce(((e,t)=>e+t),0)/i.qual.length/Bt):e.fillStyle=vt,a=""==i.s?i.len:1==i.s.length?i.s:i.s.length,e.fillText(a,o,n.y+t.stackheight*(s.on2ndrow||0)+t.stackheight/2)}}}}async function qn(e,t,n){const s=yn(e.qual),r=['<td style="color:black;text-align:left">Read</td>'];for(const t of e.boxes)for(let n=0;n<t.len;n++){e.seq[t.cidx+n];r.push('<td style="background:'+rt(s[t.cidx+n]/Bt)+'">'+e.seq[t.cidx+n]+"</td>")}const o=[];o.push('<li><span style="background:'+ht+';color:white">This segment in template is unmapped</span></li>'),1&e.flag&&o.push("<li>Template has multiple segments</li>"),2&e.flag&&o.push("<li>Each segment properly aligned</li>"),16&e.flag&&o.push("<li>Reverse complemented</li>"),32&e.flag&&o.push("<li>Next segment in the template is reverse complemented</li>"),64&e.flag&&o.push("<li>This is the first segment in the template</li>"),128&e.flag&&o.push("<li>This is the last segment in the template</li>"),256&e.flag&&o.push("<li>Secondary alignment</li>"),512&e.flag&&o.push("<li>Not passing filters</li>"),1024&e.flag&&o.push("<li>PCR or optical duplicate</li>"),2048&e.flag&&o.push("<li>Supplementary alignment</li>");let i={seq:e.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center">\n\t\t\t  <tr style="color:white">${r.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE</span>: ${Math.abs(e.seq.length)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${e.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${e.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${e.qname}</span>\n\t\t  </div>\n\t\t  <ul style='padding-left:15px'>${o.join("")}</ul>`};return e.discord_unmapped2&&(i.unmapped_mate=!0),i}async function xn(e,t,n){const s=e.boxes[0].start,r=e.boxes[e.boxes.length-1],o=r.start+r.len,i=await hn(t,n.chr+":"+(s+1)+"-"+o),a=yn(e.qual);let l,c;if("*"==e.seq)l=["<td>Nucleotide sequence not available for this read</td>"],c=["<td></td>"];else{l=["<td>Reference</td>"],c=['<td style="color:black;text-align:left">Read</td>'];for(const t of e.boxes)if("H"!=t.opr)if("I"!=t.opr)if("D"!=t.opr&&"N"!=t.opr)if("S"!=t.opr)if("M"!=t.opr&&"="!=t.opr&&"X"!=t.opr&&"*"!=t.opr);else for(let n=0;n<t.len;n++){const r=i[t.start-s+n],o=e.seq[t.cidx+n];l.push("<td>"+r+"</td>"),"*"==e.qual?c.push('<td style="color:black;background:'+(r.toUpperCase()==o.toUpperCase()?rt:ut)+'">'+e.seq[t.cidx+n]+"</td>"):c.push('<td style="background:'+(r.toUpperCase()==o.toUpperCase()?rt:ut)(a[t.cidx+n]/Bt)+'">'+e.seq[t.cidx+n]+"</td>")}else for(let n=0;n<t.len;n++)l.push("<td>"+i[t.start-s+n]+"</td>"),"*"==e.qual?c.push('<td style="background:'+mt(1)+'">'+e.seq[t.cidx+n]+"</td>"):c.push('<td style="background:'+mt(a[t.cidx+n]/Bt)+'">'+e.seq[t.cidx+n]+"</td>");else if(t.len>=Yt)l.push('<td style="font-size:.8em;opacity:.5;white-space:nowrap">'+t.len+" bp</td>"),c.push('<td style="color:black;white-space:nowrap">-----------</td>');else for(let e=0;e<t.len;e++)l.push("<td>"+i[t.start-s+e]+"</td>"),c.push('<td style="color:black">-</td>');else for(let n=t.cidx;n<t.cidx+t.len;n++)l.push("<td>-</td>"),"*"==e.qual?c.push('<td style="color:'+vt+';background:white">'+e.seq[n]+"</td>"):c.push('<td style="color:'+vt+";background:"+rt(a[n]/Bt)+'">'+e.seq[n]+"</td>")}let f=0,u=0,d=[],p=[],m=0;for(const t of e.boxes)f=u,u+=t.len,"S"==t.opr&&(m=1,d.push(f),p.push(u));const h=[];e.rnext&&h.push('<li>Next segment on <span style="background:'+ot+'">'+(n.nochr?"chr":"")+e.rnext+", "+e.pnext+"</span></li>"),e.discord_wrong_insertsize&&e.discord_orientation?h.push('<li><span style="background:'+at+';color:white">Wrong insert size</span> mate position: '+e.pnext+'</li><li><span style="background:'+yt+';color:white">Segments also having wrong orientation</span> '+e.discord_orientation_direction+"</li>"):e.discord_wrong_insertsize?h.push('<li><span style="background:'+at+';color:white">Wrong insert size</span> mate position: '+e.pnext+"</li>"):e.discord_orientation?h.push('<li><span style="background:'+yt+';color:white">Segments having wrong orientation</span> '+e.discord_orientation_direction+"</li>"):e.discord_unmapped2&&h.push('<li><span style="background:'+ht+';color:white">Other segment in template is unmapped</span></li>'),1&e.flag&&h.push("<li>Template has multiple segments</li>"),2&e.flag&&h.push("<li>Each segment properly aligned</li>"),16&e.flag&&h.push("<li>Reverse complemented</li>"),32&e.flag&&h.push("<li>Next segment in the template is reverse complemented</li>"),64&e.flag&&h.push("<li>This is the first segment in the template</li>"),128&e.flag&&h.push("<li>This is the last segment in the template</li>"),256&e.flag&&h.push("<li>Secondary alignment</li>"),512&e.flag&&h.push("<li>Not passing filters</li>"),1024&e.flag&&h.push("<li>PCR or optical duplicate</li>"),2048&e.flag&&h.push("<li>Supplementary alignment</li>");let g={seq:e.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center;font-family:courier">\n\t\t\t  <tr style="opacity:.6">${l.join("")}</tr>\n\t\t\t  <tr style="color:white">${c.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">CHR</span>: ${n.chr.replace("chr","")},\n\t\t\t<span style="opacity:.5;font-size:.7em">START</span>: ${e.segstart_original+1},\n\t\t\t<span style="opacity:.5;font-size:.7em">STOP</span>: ${o},\n\t\t\t<span style="opacity:.5;font-size:.7em">READ LENGTH</span>: ${e.seq.length} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE LENGTH</span>: ${Math.abs(e.tlen)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${e.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${e.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${e.qname}</span>\n\t\t  </div>\n\t\t  <ul style='padding-left:15px'>${h.join("")}</ul>`,start_readpos:s+1,boxes:e.boxes,readpanel_DN_maxlength:Yt};return 1==m&&(g.soft_starts=d,g.soft_stops=p),e.discord_unmapped2&&(g.unmapped_mate=!0),g}function Nn(e){const t=Le().createHmac("md5",Qt),n=[e.get("X-Auth-Token")||e.cookies.sessionid,e.query.gdcFileUUID,e.query.gdcFilePosition];return t.update(n.join("")).digest("hex")+".bam"}async function Sn(e){if(!e.query.gdcFileUUID||!e.query.gdcFilePosition||!e.query.file)throw"cannot download GDC BAM slice: request is unauthorized";const t=e.query.regions;if(!Array.isArray(t)||0==t.length)throw"req.query.regions[] not non-empty array";const n=[];for(const s of t){const t=await Rn(s.chr,s.start,s.stop,e.query.gdcFileUUID,Nn(e),e);n.push({filesize:t})}return n}const An=r().features?.bamCache||{},Cn=An.maxAge||72e5,jn=An.maxSize||5e9,Tn=An.checkWait||6e4;let Mn,On=0;function In(e=0){const t=Date.now()+e;if(Mn){if(On&&On<=t+5)return;clearTimeout(Mn),Mn=void 0}On=t,console.log(`will trigger mayDeleteCacheFiles() in ${e} ms`),Mn=setTimeout(En,e)}async function En(){console.log("checking for cached bam files to delete ...");try{const e=Date.now()-Cn,t=await h().promises.readdir(r().cachedir_bam),n=[];let s=0,o=0,i=0,a=0;for(const l of t){if(!l.endsWith(".bam")&&!l.endsWith(".bai"))continue;i++;const t=y().join(r().cachedir_bam,l),c=await 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rs=n(8877),os=n(1575);const is="ssm_occurrence_centrics";async function as(e){const t=new Map,{host:n,headers:s}=e.getHostHeaders(),o=y().join(n.rest,"ssm_occurrences/_mapping");let i;try{const{body:e}=await(0,F.fk)(o,{headers:s});i=e}catch(e){throw console.log(e),"failed to get GDC API _mapping: "+(e.message||e)}if(!i._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(i.fields))throw".fields not array";if(!Array.isArray(i.nested))throw".nested not array";const a=new Set(i.nested);let l=0,c=0,f=0,u=0,d=0,p=0;for(const e of i.fields){if(ds(e)){l++;continue}const n=e.split(".");for(let e=1;e<n.length;e++){const s=n.slice(0,e).join("."),r=s+"."+n[e],o=n[e][0].toUpperCase()+n[e].slice(1).replace(/_/g," "),l={id:r.toLowerCase(),name:o,included_types_set:new Set,child_types_set:new Set};if(e==n.length-1){l.isleaf=!0;const 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Unknown variable type: "+e.type)),l.type||c++,ls(l)}if(1==e);else if(l.parent_id=s,l.type){l.included_types_set.add(l.type);let e=t.get(s);for(;e&&(e.included_types_set.add(l.type),e.child_types_set.add(l.type),e.parent_id);)e=t.get(e.parent_id)}a.has(r)&&(l.isObjectList=!0),t.set(r,l)}}try{await async function(e,t){const n=[],s=new Map;for(const t of e.values()){if("integer"!=t.type&&"float"!=t.type)continue;if(fs[t.id]){t.bins=fs[t.id];continue}const e=t.id.replace("case.","").replace(/\./g,"__");s.set(e,t.id),n.push(e+" {\n\t\t   stats {\n\t\t\t\tMin : min\n\t\t\t\tMax: max\n\t\t\t\tMean: avg\n\t\t\t\tSD: std_deviation\n\t\t\t\tcount\n\t\t\t}\n\t\t\trange(ranges: $filters2) {\n\t\t\t  buckets {\n\t\t\t\tdoc_count\n\t\t\t\tkey\n\t\t\t  }\n\t\t\t}\n\t\t}")}if(0==n.length)throw"GDC: no numeric terms, should not happen";const r=`\n\t  query ContinuousAggregationQuery($caseFilters: FiltersArgument, $filters: FiltersArgument, $filters2: FiltersArgument) {\n\t  viewer {\n\t\texplore 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o=(r.Max-r.Min)/5,l="integer"==s.type?Math.ceil(o):o;s.bins={default:{mode:"discrete",type:"regular-bin",bin_size:l,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:r.Min+l}}},i++}console.log(`GDC default binning: ${i} assigned, ${a} unassigned`)}(t,e)}catch(e){throw console.log(e),"assignDefaultBins() failed: "+(e.message||e)}for(const e of t.values())e.type||p++,e.included_types=[...e.included_types_set],e.child_types=[...e.child_types_set],delete e.included_types_set,delete e.child_types_set;console.log("GDC dictionary:",t.size,"total variables,",l,"lines skipped,",c,"lines with unknown term type,","categorical="+f,"integer="+u,"float="+d,"parent="+p),Object.freeze(t),function(e,t){const n=e.cohort.termdb.q={};async function s(t,n){if(0==t.length||!n)return;const s=await e.termdb.termid2totalsize2.get(t.map((e=>e.id)),JSON.parse(n));for(const e of t)if(e){const t=s.get(e.id);"categorical"==e.type&&t?t.length?e.samplecount=t.map((e=>e[1])).reduce(((e,t)=>e+t)):(e.disabled=!0,e.samplecount=0):"integer"!=e.type&&"float"!=e.type||(e.samplecount=t.total,0==t.total&&(e.disabled=!0))}}n.getRootTerms=async(e,n=null)=>{const r=[];for(const e of t.values())null==e.parent_id&&r.push(JSON.parse(JSON.stringify(e)));return await s(r,n),r},n.getTermChildren=async(e,n=null,r=null)=>{const o=[];for(const n of t.values())n.parent_id==e&&o.push(JSON.parse(JSON.stringify(n)));return await s(o,r),o},n.findTermByName=async(e,n=null,r,o=null,i=null)=>{(e=e.toLowerCase()).includes(" ")&&(e=e.replace(/\s/g,"_"));const a=[];for(const n of t.values())i&&!(0,os.CG)(n,i)||n.id.includes(e)&&a.push(JSON.parse(JSON.stringify(n)));return await s(a,o),a},n.getAncestorIDs=e=>{if(!t.has(e))return;const n=e.split("."),s=[];for(let e=1;e<n.length;e++)s.push(n.slice(0,e+1).join("."));return s},n.getAncestorNames=n.getAncestorIDs,n.termjsonByOneid=e=>{const n=t.get(e);return n?JSON.parse(JSON.stringify(n)):null},n.getSupportedChartTypes=()=>{const e={},n={};for(const s of t.values())s.type&&(s.cohort in e||(e[s.cohort]=["barchart","table","regression"],n[s.cohort]=0),"survival"!=s.type||e[s.cohort].includes("survival")||e[s.cohort].push("survival"),"condition"!=s.type||e[s.cohort].includes("cuminc")||e[s.cohort].push("cuminc"),"float"!=s.type&&"integer"!=s.type||(n[s.cohort]+=s.samplecount));for(const t in n)n[t]>0&&e[t].push("boxplot"),n[t]>1&&e[t].push("scatterplot");return e}}(e,t),e.cohort.termdb.termtypeByCohort=[],f&&e.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),u&&e.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),d&&e.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),e.__gdc={aliquot2submitter:{cache:new Map,get:async t=>e.__gdc.aliquot2submitter.cache.has(t)?e.__gdc.aliquot2submitter.cache.get(t):t},map2caseid:{cache:new Map,get:t=>e.__gdc.map2caseid.cache.get(t)},caseid2submitter:new Map,caseIds:new Set,casesWithExpData:new Set,gdcOpenProjects:new Set,doneCaching:0};try{await async function(e){const t={filters:{op:"and",content:[{op:"=",content:{field:"access",value:"open"}},{op:"=",content:{field:"data_type",value:"Masked Somatic Mutation"}}]},facets:"cases.project.project_id",size:0},{host:n,headers:s}=e.getHostHeaders(),{body:r}=await(0,F.fk)(y().join(n.rest,"files"),{method:"POST",headers:s,body:t});if(!Array.isArray(r?.data?.aggregations?.["cases.project.project_id"]?.buckets))return void console.log("getting open project_id but return is not re.data.aggregations['cases.project.project_id'].buckets[]");for(const t of r.data.aggregations["cases.project.project_id"].buckets)t.key&&e.__gdc.gdcOpenProjects.add(t.key);console.log("GDC open-access projects:",e.__gdc.gdcOpenProjects.size)}(e)}catch(e){throw console.log(e),"getOpenProjects() failed: "+(e.message||e)}!async function(e){await async function(e){const{host:t,headers:n}=e.getHostHeaders();try{{const e=y().join(t.rest,"ssms"),n=await ps(e);if(n)throw`${e} returns error code: ${n}`}{const e=y().join(t.rest,"ssm_occurrences"),n=await ps(e);if(n)throw`${e} returns error code: ${n}`}{const e=y().join(t.rest,"cases"),n=await ps(e);if(n)throw`${e} returns error code: ${n}`}{const e=y().join(t.rest,"files"),n=await ps(e);if(n)throw`${e} returns error code: ${n}`}{const e=y().join(t.rest,"analysis/top_mutated_genes_by_project"),n=await ps(e);if(n)throw`${e} returns error code: ${n}`}{const e=await async function(e,t){const n=new Date;try{const n="query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\tprimary_site {buckets { doc_count, key }}\n\t\t\t\t}\n\t\t\t}\n\t\t}}",s=await v().post(e,{headers:t,body:JSON.stringify({query:n,variables:{}})});if(s.statusCode>399)return s.statusCode}catch(t){if(console.log(t),t.code)return t.code;throw"see above error from graphql API "+e}console.log("GDC GraphQL API okay: "+e,new Date-n,"ms")}(t.graphql,JSON.parse(JSON.stringify(n)));if(e)throw`${t.graphql} returns error code: ${e}`}}catch(e){throw console.log(e),`\n##########################################\n#\n#   Some GDC API unavailable, see error above\n#   ${t.rest}\n#   ${t.graphql}\n#\n##########################################`}}(e);try{await async function(e){if("stopGdcCacheAliquot"in r().features){if(!Number.isInteger(r().features.stopGdcCacheAliquot))return void console.log("GDC: sample IDs are not cached!");console.log("GDC: running limited sample ID caching")}else console.log("GDC: caching complete sample ID mapping");const t=1e3,n=await ms(e,1,0);if(!Number.isInteger(n))throw"totalCases not integer";const s=new Date;console.log("GDC: Start to cache sample IDs of",n,"cases...");for(let s=0;s<Math.ceil(n/t)&&(await ms(e,t,1e3*s),!(Number.isInteger(r().features.stopGdcCacheAliquot)&&s>=r().features.stopGdcCacheAliquot));s++);await async function(e){const{host:t,headers:n}=e.getHostHeaders(),s=`${t.geneExp}/gene_expression/availability`;try{const t=[...e.__gdc.caseIds],{body:r}=await(0,F.fk)(s,{method:"post",headers:n,body:{case_ids:t,gene_ids:["ENSG00000141510"]}});if(!Array.isArray(r.cases?.details))throw"re.cases.details[] not array";for(const t of r.cases.details)t.has_gene_expression_values&&e.__gdc.casesWithExpData.add(t.case_id);delete e.__gdc.caseIds}catch(e){console.log("You don't have access to /gene_expression/availability/, you cannot run GDC hierCluster")}}(e),e.__gdc.doneCaching=!0,console.log("GDC: Done caching sample IDs. Time:",Math.ceil((new Date-s)/1e3),"s"),console.log("\t",e.__gdc.aliquot2submitter.cache.size,"aliquot IDs to sample submitter id,"),console.log("\t",e.__gdc.caseid2submitter.size,"case uuid to submitter id,"),console.log("\t",e.__gdc.map2caseid.cache.size,"different ids to case uuid,"),console.log("\t",e.__gdc.casesWithExpData.size,"cases with gene expression data.")}(e)}catch(e){throw e.stack&&console.log(e.stack),"cacheSampleIdMapping() failed: "+(e.message||e)}}(e)}function ls(e){"case.diagnoses.age_at_diagnosis"!=e.id||(e.valueConversion={scaleFactor:1/365,fromUnit:"day",toUnit:"year"})}const cs={default:{mode:"discrete",type:"regular-bin",bin_size:1,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:0},last_bin:{start:1,stopunbounded:!0}}},fs={"case.diagnoses.age_at_diagnosis":{default:{type:"custom-bin",mode:"discrete",lst:[{startunbounded:!0,stop:10950,stopinclusive:!0,label:"<=30 years"},{start:10950,stop:21900,stopinclusive:!0,label:"30-60 years"},{start:21900,stopunbounded:!0,startinclusive:!1,label:">60years"}]}}};const us=new Set(["case.consent_type","case.days_to_consent","case.days_to_index"]);function ds(e){return!!(e.startsWith("ssm")||e.startsWith("case.observation")||e.startsWith("case.available_variation_data"))||(!(!e.endsWith("_id")||e.endsWith("project_id"))||(!!us.has(e)||void 0))}async function ps(e){try{const t=new Date,n=await v()(e);if(n.statusCode>399)return n.statusCode;console.log("GDC API okay: "+e,new Date-t,"ms")}catch(t){if(console.log("See error from",e),console.log(t),t.code)return t.code;throw"gdc api down: "+e}}async function ms(e,t,n,s){const r=["fields=submitter_id,samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(s)r.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+s+'"]}}]}');else{if(!Number.isInteger(t)||!Number.isInteger(n))throw"size and from not 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hs=n(4973),gs=n(3625),ys=n(478),bs=n(8907),vs=n(394);function ws(e,t){if(t.updateAttr&&!e.label){for(const n of t.updateAttr){let t=e;for(const e of n)if(t)if("object"==typeof e)for(const n in e)t[n]=e[n];else t=t[e]}e.label&&delete t.updateAttr}}function _s(e,t,n){if(!e.cohort?.db?.refresh)return;const s=e.cohort.db.refresh;delete e.cohort.db.refresh,t.get(`${n}/${s.route}`,(async(t,n)=>{n.send({label:e.label,files:[]})})),t.post(`${n}/${s.route}`,(async(t,n)=>{try{const s=e.cohort.db?.file?.startsWith(r().tpmasterdir)?e.cohort.db.file:y().join(r().tpmasterdir,e.cohort.db.file||""),o=t.body;if(!o.dbfile)throw"Updating input text files via the termdb-refresh page has been deprecated.Please use the buildTermdb.bundle.js. pipeline before triggering this route to replace the db file.";{const t=y().join(r().tpmasterdir,o.dbfile);if(!await h().stat(t))throw`dbfile not found: '${t}'`;const n=e.cohort.db.file_fullpath||s;if(t===n)throw"db file source and target are the same";console.log(`copying ${t} to ${n}`),await h().copyFile(t,n)}await Is(e),n.send({status:"ok"})}catch(e){console.log(e),n.send({error:e.error||e})}}))}var ks=n(2188),qs=n(2974),xs=n(3795),Ns=n(7934),Ss=n(5057),As=n(3677),Cs=n(4924),js=n(901);const Ts="Unannotated";async function Ms(e,t,n,s=null,o=null){await Is(e),e.queries&&(await async function(e,t){const n=e.queries.snvindel;if(!n)return;if(n.url){if(!n.url.base)throw".snvindel.url.base missing";if(!n.url.key)throw".snvindel.url.key missing"}if(!n.byisoform&&!n.byrange)throw"byisoform and byrange are both missing on queries.snvindel";if(n.byrange)if(n.byrange.gdcapi)Pn.xq(e);else if(n.byrange.bcffile)n.byrange.bcffile=n.byrange.bcffile.startsWith(r().tpmasterdir)?n.byrange.bcffile:y().join(r().tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await Fs(e,t),n.byrange._tk?.samples.length||delete n.byrange._tk.samples,Rs(e,n.byrange._tk.samples,"snvindel.byrange.bcffile");else{if(!n.byrange.chr2bcffile)throw"unknown query method for queries.snvindel.byrange";n.byrange._tk={chr2files:{}};for(const e in n.byrange.chr2bcffile)n.byrange._tk.chr2files[e]={file:y().join(r().tpmasterdir,n.byrange.chr2bcffile[e])};delete n.byrange.chr2bcffile,n.byrange.get=await Fs(e,t),n.byrange._tk.samples.length||delete n.byrange._tk.samples,Rs(e,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";Pn.CN(e)}if(n.m2csq){if(!n.m2csq.by)throw".by missing from queries.snvindel.m2csq";if("ssm_id"!=n.m2csq.by)throw"unknown value of queries.snvindel.m2csq.by";if(!n.m2csq.gdcapi)throw"unknown query method for queries.snvindel.m2csq";Pn.wm(e)}}(e,t),await async function(e,t){const n=e.queries.svfusion;if(!n)return;if(!n.byrange)throw"byrange missing from queries.svfusion";if(n.byrange){if(!n.byrange.file)throw"unknown query method for svfusion.byrange";n.byrange.file=n.byrange.file.startsWith(r().tpmasterdir)?n.byrange.file:y().join(r().tpmasterdir,n.byrange.file),n.byrange.get=await async function(e,t){const n=e.queries.svfusion.byrange;if(n.file)await F.LC(n.file);else{if(!n.url)throw"file and url both missing on svfusion.byrange{}";n.dir=await F.d1(n.url,n.indexURL)}n.nochr=await F.Jy(n.file||n.url,null,t);{const e=await F.ZD(n.file);if(!e[0])throw"header line missing from "+n.file;const t=e[0].split(" ");if("#sample"!=t[0])throw"header line not starting with #sample: "+n.file;n.samples=t.slice(1).map((e=>({name:e})))}return async t=>{if(!Array.isArray(t.rglst))throw"q.rglst[] is not array";if(0==t.rglst.length)throw"q.rglst[] blank array";const s=$s(t),r=await(0,js.T)(t,n.samples,e);if(0==r?.size)return[];const o=new Map;for(const e of t.rglst)await F.UE({args:[n.file||n.url,(n.nochr?e.chr.replace("chr",""):e.chr)+":"+e.start+"-"+e.stop],dir:n.dir,callback:n=>{const i=n.split("\t"),a=Number(i[1]);let l,c,f,u,d;try{l=JSON.parse(i[3])}catch(e){return}if(l.dt!=$.dtfusionrna&&l.dt!=$.dtsv)return;if(l.class=l.dt==$.dtsv?$.mclasssv:$.mclassfusionrna,t.hiddenmclass&&t.hiddenmclass.has(l.class))return;if(l.sample&&r&&!r.has(l.sample))return;if(l.chrA)c=1,f=l.geneA||l.chrA,u=l.strandA,d=[{a:{chr:l.chrA,pos:l.posA,strand:l.strandA,name:l.geneA},b:{chr:e.chr,pos:a,strand:l.strandB,name:l.geneB}}];else if(l.chrB)c=0,f=l.geneB||l.chrB,u=l.strandB,d=[{a:{chr:e.chr,pos:a,strand:l.strandA,name:l.geneA},b:{chr:l.chrB,pos:l.posB,strand:l.strandB,name:l.geneB}}];else{if(!l.pairlst)throw"missing chrA and chrB";{d=l.pairlst;const e=l.pairlst.findIndex((e=>e.chr==chr&&e.pos==a));if(-1==e)throw"current point missing from pairlst";c=e}}const p=[l.dt,e.chr,a,u,c,encodeURIComponent(f)].join(hs.dq);let m;if(l.sample&&(m={sample_id:l.sample},l.mattr)){if(s)for(const e in s){const t=e in l.mattr?l.mattr[e]:Ts;if(s[e].has(t))return}t.addFormatValues&&(m.formatK2v=l.mattr)}o.has(p)||o.set(p,{ssm_id:p,dt:l.dt,class:l.class,chr:e.chr,pos:a,strand:u,pairlstIdx:c,mname:f,pairlst:d,samples:[]}),m&&o.get(p).samples.push(m)}});return[...o.values()]}}(e,t),Rs(e,n.byrange.samples,"svfusion.byrange")}}(e,t),await async function(e,t){const n=e.queries.geneCnv;if(!n)return;if(!n.bygene)throw"geneCnv.bygene missing";n.bygene.gdcapi&&Pn.IK(e)}(e),await async function(e,t){const n=e.queries.cnv;if(!n)return;if(!n.byrange)throw"queries.cnv.byrange{} missing";if("native"==n.byrange.src){if(!n.byrange.file)throw"cnv.byrange.file missing when src=native";return n.byrange.file=n.byrange.file.startsWith(r().tpmasterdir)?n.byrange.file:y().join(r().tpmasterdir,n.byrange.file),n.byrange.get=await async function(e,t){const n=e.queries.cnv.byrange;if(n.file)await F.LC(n.file);else{if(!n.url)throw"file and url both missing on cnv.byrange{}";n.dir=await F.d1(n.url,n.indexURL)}n.nochr=await F.Jy(n.file||n.url,null,t);{const e=await F.ZD(n.file);if(!e[0])throw"header line missing from "+n.file;const t=e[0].split(" ");if("#sample"!=t[0])throw"header line not starting with #sample: "+n.file;n.samples=t.slice(1).map((e=>({name:e})))}return async t=>{if(!Array.isArray(t.rglst))throw"q.rglst[] is not array";if(0==t.rglst.length)throw"q.rglst[] blank array";if(t.cnvMaxLength&&!Number.isInteger(t.cnvMaxLength))throw"cnvMaxLength is not integer";if(t.cnvGainCutoff&&!Number.isFinite(t.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(t.cnvLossCutoff&&!Number.isFinite(t.cnvLossCutoff))throw"cnvLossCutoff is not finite";const s=$s(t),r=await(0,js.T)(t,n.samples,e);if(0==r?.size)return[];const o=[];for(const e of t.rglst)await F.UE({args:[n.file||n.url,(n.nochr?e.chr.replace("chr",""):e.chr)+":"+e.start+"-"+e.stop],dir:n.dir,callback:n=>{const i=n.split("\t"),a=Number(i[1]),l=Number(i[2]);if(t.cnvMaxLength&&l-a>=t.cnvMaxLength)return;let c;try{c=JSON.parse(i[3])}catch(e){return}if(c.dt==$.dtcnv){if(c.chr=e.chr,c.start=a,c.stop=l,Number.isFinite(c.value)){if(c.value>0&&t.cnvGainCutoff&&c.value<t.cnvGainCutoff)return;if(c.value<0&&t.cnvLossCutoff&&c.value>t.cnvLossCutoff)return;c.class=c.value>0?$.mclasscnvgain:$.mclasscnvloss}else if(c.class!=$.mclasscnvgain&&c.class!=$.mclasscnvloss)return;if(c.ssm_id=[e.chr,c.start,c.stop,c.class].join(hs.dq),(!t.hiddenmclass||!t.hiddenmclass.has(c.class))&&(!c.sample||!r||r.has(c.sample))){if(c.sample){const e={sample_id:c.sample};if(c.mattr){if(s)for(const e in s){const t=e in c.mattr?c.mattr[e]:Ts;if(s[e].has(t))return}t.addFormatValues&&(e.formatK2v=c.mattr)}delete c.sample,c.samples=[e]}o.push(c)}}}});return o}}(e,t),void Rs(e,n.byrange.samples,"cnv.byrange")}throw"unknown cnv.byrange.src"}(e,t),await async function(e,t){const n=e.queries.ld;if(!n)return;if(!Array.isArray(n.tracks)||!n.tracks.length)throw"ld.tracks[] not nonempty array";for(const e of n.tracks){if(!e.name)throw"name missing from one of ld.tracks[]";if(!e.file)throw".file missing from one of ld.tracks[]";e.file0=e.file,e.file=y().join(r().tpmasterdir,e.file),await F.LC(e.file),e.nochr=await F.Jy(e.file,null,t)}if(!n.overlay)throw"ld.overlay{} missing";if(!n.overlay.color_0)throw"ld.overlay.color_0 missing";if(!n.overlay.color_1)throw"ld.overlay.color_1 missing"}(e,t),await(0,Cs.validate_query_geneExpression)(e,t),await async function(e,t){const n=e.queries.rnaseqGeneCount;if(!n)return;if(!n.file)throw"unknown data type for rnaseqGeneCount";n.file=y().join(r().tpmasterdir,n.file);{const t=(await(s=n.file,new Promise(((e,t)=>{const n=[],r=[],o=(0,x.spawn)("head",["-1",s]);o.stdout.on("data",(e=>n.push(e.toString()))),o.stderr.on("data",(e=>r.push(e.toString()))),o.on("error",(e=>{r.length&&t(r.join(""))})),o.on("close",(s=>{0!=s&&t("head command exited with non-zero status and this error: "+r.join("")),e(n.join(""))}))})))).trim().split("\t").slice(4);n.allSampleSet=new Set(t);const r=[];for(const t of n.allSampleSet)e.cohort.termdb.q.sampleName2id(t)||r.push(t);console.log(n.allSampleSet.size,`rnaseqGeneCount samples from ${e.label}`)}var s;n.get=async function(t){if(2!=t.samplelst?.groups?.length)throw".samplelst.groups.length!=2";if(t.samplelst.groups[0].values?.length<1)throw"samplelst.groups[0].values.length<1";if(t.samplelst.groups[1].values?.length<1)throw"samplelst.groups[1].values.length<1";const s=[];let o=0;for(const r of t.samplelst.groups[0].values){if(!Number.isInteger(r.sampleId))continue;const t=e.cohort.termdb.q.id2sampleName(r.sampleId);t&&(n.allSampleSet.has(t)?s.push(t):o+=1)}const i=[];let a=0;for(const s of t.samplelst.groups[1].values){if(!Number.isInteger(s.sampleId))continue;const t=e.cohort.termdb.q.id2sampleName(s.sampleId);t&&(n.allSampleSet.has(t)?i.push(t):a+=1)}const l=s.length,c=i.length;if(l<1)throw"sample size of group1 < 1";if(c<1)throw"sample size of group2 < 1";const f={case:s.map((e=>e)).join(","),control:i.map((e=>e)).join(","),input_file:n.file,output_path:y().join(r().binpath,"utils")},u=8;let d;if(s.length<=u&&i.length<=u||"edgeR"==t.method){const e=new Date,n=(await async function(e,t){return new Promise(((n,s)=>{y().join(r().Rscript,e);const o=(0,x.spawn)(r().Rscript,[e]),i=[],a=[];try{je.Readable.from(t).pipe(o.stdin)}catch(t){o.kill();let n=t;a.length&&(n+=`killed edgeR('${e}'), stderr: ${a.join("").trim()}`),s(n)}o.stdout.on("data",(e=>i.push(e))),o.stderr.on("data",(e=>a.push(e))),o.on("error",(t=>{a.length&&console.log(`edgeR('${e}') ps.on('error') stderr:`,a),s(t)})),o.on("close",(t=>{0!==t?s(`spawned '${e}' exited with a non-zero status and this stderr:\n${a.join("")}`):n(i.toString())}))}))}(y().join(r().binpath,"utils","edge.R"),JSON.stringify(f)),new Date);console.log("Time taken to run edgeR:",n-e,"ms"),t.method="edgeR";const s=y().join(r().binpath,"utils","r_output.txt");d=JSON.parse(h().readFileSync(s,"utf8")),h().unlink(s,(()=>{}))}else if("wilcoxon"==t.method){const e=new Date,n=await(0,_e.run_rust)("DEanalysis",JSON.stringify(f)),s=new Date;for(const e of n.split("\n"))e.startsWith("adjusted_p_values:")&&(d=JSON.parse(e.replace("adjusted_p_values:","")));console.log("Time taken to run rust DE pipeline:",s-e,"ms"),t.method="wilcoxon"}else{const e=new Date,n=await(0,_e.run_rust)("DEanalysis",JSON.stringify(f)),s=new Date;for(const e of n.split("\n"))e.startsWith("adjusted_p_values:")&&(d=JSON.parse(e.replace("adjusted_p_values:","")));console.log("Time taken to run rust DE pipeline:",s-e,"ms"),t.method="wilcoxon"}return{data:d,sample_size1:l,sample_size2:c,method:t.method}}}(e),await(0,As.validate_query_singleSampleMutation)(e,t),await async function(e,t){const n=e.queries.singleSampleGenomeQuantification;if(!n)return;for(const s in n){if(!Number.isFinite(n[s].min))throw"min not a number";if(!Number.isFinite(n[s].max))throw"max not a number";if(n[s].min>=n[s].max)throw"min>=max";if(!n[s].folder)throw"unknown query method for singleSampleGenomeQuantification";n[s].get=async(o,i)=>{let a=o;if(e.cohort?.termdb?.q?.sampleName2id&&(a=e.cohort.termdb.q.sampleName2id(o),null==a))return[];const l=y().join(r().tpmasterdir,n[s].folder,a.toString());try{await h().promises.stat(l)}catch(e){if("EACCES"==e.code)throw"cannot read file, permission denied";if("ENOENT"==e.code)throw"no data for this sample";throw"failed to load data"}return await zs(l,t,n[s],i)}}}(e,t),await async function(e,t){const n=e.queries.singleSampleGbtk;if(!n)return;for(const t in n){if(!Number.isFinite(n[t].min))throw"min not a number";if(!Number.isFinite(n[t].max))throw"max not a number";if(n[t].min>=n[t].max)throw"min>=max";if(!n[t].folder)throw"unknown query method for singleSampleGbtk";n[t].get=async s=>{let o=s;if(e.cohort?.termdb?.q?.sampleName2id&&(o=e.cohort.termdb.q.sampleName2id(s),null==o))return{};const i=y().join(n[t].folder,o+".gz");try{return await h().promises.stat(y().join(r().tpmasterdir,i)),{path:i}}catch(e){return{}}}}}(e),await(0,Ns.validate_query_singleCell)(e,t),await(0,Ss.validate_query_TopVariablyExpressedGenes)(e,t),await(0,hs.uK)(e),await function(e){if(!e.ssm2canonicalisoform)return;if(e.ssm2canonicalisoform.gdcapi)return void Pn.vK(e.ssm2canonicalisoform,e.getHostHeaders);throw"ssm2canonicalisoform.gdcapi is false"}(e),await function(e,t){if(!t.genedb.hasTable_refseq2ensembl)return;e.refseq2ensembl_query=t.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?")}(e,t),await function(e,t){if(!e.queries.snvindel&&!e.queries.svfusion&&!e.queries.geneCnv)return;e.mayGetGeneVariantData=async(n,s)=>{if("object"!=typeof n.term)throw"tw.term{} is not object";if("geneVariant"!=n.term.type)throw"tw.term.type is not geneVariant";if("string"!=typeof n.term.name)throw"tw.term.name is not string";if(!n.term.name)throw"tw.term.name should be gene symbol but is empty string";const r=[];if("snp"==n.term.subtype){if(!e.queries.snvindel?.allowSNPs)throw"snvindel does not allow snp";const o=(await Js(e,n.term,t,s)).find((e=>n.term.alleles.includes(e.ref)&&n.term.alleles.includes(e.alt)));if(o){const e=[];for(const t of o.samples){if(!t.formatK2v?.GT)continue;const n=[];for(const e of t.formatK2v.GT.split("/"))0==e?n.push(o.ref):1==e?n.push(o.alt):console.log("unknown allele idx");n.join("/"),n.join("/");e.push({sample_id:t.sample_id,GT:n.join("/")})}const t={samples:e};r.push(t)}}else{if(e.queries.snvindel){const o=await Js(e,n.term,t,s);r.push(...o)}if(e.queries.svfusion){const o=await async function(e,t,n,s){const r={addFormatValues:!0,filter0:s.filter0,filterObj:s.filter,sessionid:s.sessionid};if(e.queries.svfusion.byrange)return await Us(t,n),r.rglst=[t],await e.queries.svfusion.byrange.get(r);throw"unknown queries.svfusion method"}(e,n.term,t,s);r.push(...o)}if(e.queries.cnv){const o=await async function(e,t,n,s){const r={addFormatValues:!0,filter0:s.filter0,filterObj:s.filter,cnvMaxLength:t?.q?.cnvMaxLength,cnvGainCutoff:t?.q?.cnvGainCutoff,cnvLossCutoff:t?.q?.cnvLossCutoff,sessionid:s.sessionid};if(e.queries.cnv.byrange)return await Us(t.term,n),r.rglst=[t.term],await e.queries.cnv.byrange.get(r);throw"unknown queries.cnv method"}(e,n,t,s);r.push(...o)}if(e.queries.geneCnv){const t=await async function(e,t,n,s){const r={filter0:s.filter0,sessionid:s.sessionid};if(e.queries.geneCnv.bygene)return t.name?(r.gene=t.name,await e.queries.geneCnv.bygene.get(r)):[];throw"unknown queries.geneCnv method"}(e,n.term,0,s);r.push(...t)}}const o=new Map;for(const e of r)if(Array.isArray(e.samples))for(const t of e.samples){o.has(t.sample_id)||o.set(t.sample_id,{sample:t.sample_id}),o.get(t.sample_id)[n.term.name]||(o.get(t.sample_id)[n.term.name]={key:n.term.name,label:n.term.name,values:[]});const s={gene:n.term.name,isoform:e.isoform,dt:e.dt,chr:n.term.chr,class:e.class,pos:e.pos||(e.start?e.start+"-"+e.stop:""),mname:e.mname};if("value"in e&&(s.value=e.value),t.formatK2v)for(const e in t.formatK2v)s[e]=t.formatK2v[e];e.dt==$.dtsnvindel?t.GT&&(s.value=t.GT,s.key=t.GT):e.dt!=$.dtfusionrna&&e.dt!=$.dtsv||(s.pairlst=e.pairlst),o.get(t.sample_id)[n.term.name].values.push(s)}return await async function(e,t,n,s){if(!t.assayAvailability?.byDt)return;const r=e.filter?new Set((await(0,bs.cf)(e.filter,t)).map((e=>e.id))):null;for(const e in t.assayAvailability.byDt){const o=t.assayAvailability.byDt[e];if(o.byOrigin)for(const t in o.byOrigin){Bs(e,o.byOrigin[t],n,s,t,r)}else Bs(e,o,n,s,!1,r)}}(s,e,o,n.term.name),o}}(e,t)),await function(e){if(!e.assayAvailability)return;if(e.assayAvailability.byDt)for(const t in e.assayAvailability.byDt){const n=e.assayAvailability.byDt[t];if(n.byOrigin)for(const t in n.byOrigin){const s=n.byOrigin[t];if(!s.yes||!s.no||!s.term_id)throw"ds.assayAvailability.byDt.*.byOrigin properties require .term_id .yes{} .no{}";Hs(e,s)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";Hs(e,n)}}}(e),await function(e){if(!e.viewModes)return;if(!Array.isArray(e.viewModes))throw"ds.viewModes[] not array";for(const t of e.viewModes)if(t.byInfo){if(!e?.queries?.snvindel?.info)throw"view mode byInfo but queries.snvindel.info missing";const n=e.queries.snvindel.info[t.byInfo];if(!n)throw"unknown INFO field for viewmode byInfo";if("Float"!=n.Type&&"Integer"!=n.Type)throw"viewmode byInfo Type is not numeric";t.type="numeric",t.label=t.byInfo}else if(!t.byAttribute)throw"view mode not byInfo or byAttribute"}(e),e.cohort?.db?.refresh&&s&&await _s(e,s,o)}function Os(e){const t={isMds3:!0,label:e.label};if(e.viewModes&&(t.skewerModes=e.viewModes),e.noGenomicMode4lollipopTk&&(t.noGenomicMode4lollipopTk=!0),function(e,t){if(!e.queries)return;const n={};e.queries.singleSampleMutation&&(n.singleSampleMutation={sample_id_key:e.queries.singleSampleMutation.sample_id_key,discoSkipChrM:e.queries.singleSampleMutation.discoSkipChrM});if(e.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const t in e.queries.singleSampleGenomeQuantification)n.singleSampleGenomeQuantification[t]=JSON.parse(JSON.stringify(e.queries.singleSampleGenomeQuantification[t])),delete n.singleSampleGenomeQuantification[t].folder}if(e.queries.singleSampleGbtk){n.singleSampleGbtk={};for(const t in e.queries.singleSampleGbtk)n.singleSampleGbtk[t]=JSON.parse(JSON.stringify(e.queries.singleSampleGbtk[t])),delete n.singleSampleGbtk[t].folder}const s=e.queries.snvindel;s&&(t.has_skewer=!0,n.snvindel={forTrack:s.forTrack,vcfid4skewerName:s.vcfid4skewerName,skewerRim:s.skewerRim,ssmUrl:s.ssmUrl},s.m2csq&&(n.snvindel.m2csq={by:s.m2csq.by}),s.info&&(t.bcf={info:s.info}),s.format&&(t.bcf||(t.bcf={}),t.bcf.format=s.format));if(e.queries.ld){n.ld=JSON.parse(JSON.stringify(e.queries.ld));for(const e of n.ld.tracks)delete e.file}t.queries=n}(e,t),e.cohort?.termdb&&(t.termdb={},e.cohort.termdb.allowCaseDetails&&(t.termdb.allowCaseDetails={sample_id_key:e.cohort.termdb.allowCaseDetails.sample_id_key})),e.variant2samples){const n=e.variant2samples;t.variant2samples={sunburst_twLst:n.sunburst_twLst,twLst:n.twLst,type_samples:n.type_samples,type_summary:n.type_summary,type_sunburst:n.type_sunburst,variantkey:n.variantkey}}return t}async function Is(e){if(e.cohort){if(!e.cohort.termdb)throw"ds.cohort is set but cohort.termdb{} missing";if(!e.cohort.db)throw"ds.cohort is set but cohort.db{} missing";if(!e.cohort.db.file&&!e.cohort.db.file_fullpath)throw"ds.cohort.db.file missing"}else{if(!e.termdb)return;e.cohort={},e.cohort.termdb=e.termdb,delete e.termdb}const t=e.cohort.termdb;if(t?.dictionary?.gdcapi)await as(e);else if(t?.dictionary?.dbFile)e.cohort.db={file:t.dictionary.dbFile},delete t.dictionary.dbFile,(0,vs.JV)(e);else{if(!e.cohort.db)throw"unknown method to initiate dictionary";(0,vs.JV)(e)}if(t.termid2totalsize2&&(t.termid2totalsize2.gdcapi,t.termid2totalsize2.get=async(n,s={},r=null)=>t.termid2totalsize2.gdcapi?await Pn.ws(n,s,r,e):await async function(e,t,n,s){const r=Es(t,s),o=new Map;for(const t of e)if(t.term&&"categorical"==t.term.type){const e={term1_id:t.id,term1_q:{type:"values"},filter:r},n=await(0,Ae.e8)(e,s,s.cohort.termdb);if(!n?.data?.charts?.[0])continue;const i=[];for(const e of n.data.charts[0].serieses)i.push([e.seriesId,e.total]);o.set(t.id,i)}return n?[o,n]:o}(n,s,r,e)),function(e){const t=e.selectCohort;if(!t)return;if("object"!=typeof t)throw"selectCohort{} not object";if(!t.term)throw"term{} missing from termdb.selectCohort";if(!t.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof t.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=t.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';{const n=e.q.termjsonByOneid(t.term.id);if(!n)throw"termdb.selectCohort.term.id is invalid";if("categorical"!=n.type)throw"termdb.selectCohort.term type is not categorical"}if(!t.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(t.values))throw"termdb.selectCohort.values is not array";if(0==t.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const e of t.values){if(!e.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(e.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==e.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}(t),await async function(e){if(!e.restrictAncestries)return;if(!Array.isArray(e.restrictAncestries)||0==e.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const t of e.restrictAncestries){if(!t.name)throw"name missing from one of restrictAncestries";if("object"!=typeof t.tvs)throw".tvs{} missing from one of restrictAncestries";if(!t.tvs.term)throw"tvs.term{} missing from an ancestry";if(!t.tvs.term.id)throw"tvs.term.id missing from an ancestry";{const n=e.q.termjsonByOneid(t.tvs.term.id);if(!n)throw"tvs.term.id is invalid from an ancestry";if("categorical"!=n.type)throw"tvs.term.type is not categorical from an ancestry"}if(!Number.isInteger(t.PCcount))throw"PCcount is not integer";if(t.PCcount<=1)throw"PCcount must be greater than 1";if(t.PCTermId){t.pcs=new Map;for(let n=1;n<=t.PCcount;n++){const s=t.PCTermId+n,r=e.q.termjsonByOneid(s);if(!r)throw"a PC term is not found in termdb";const o=e.q.getAllValues4term(s);if(!o||!o.size)throw"no sample PC values are retrieved by restrictAncestries term: "+s;t.pcs.set(r.name,o)}}else{if(!t.PCBySubcohort)throw"unknown PC source and configuration for restrictAncestries";for(const n in t.PCBySubcohort){let s=!0;for(const t of e.selectCohort.values)if(n==t.keys.sort().join(",")){s=!1;break}if(s)throw"unknown subcohort from PCBySubcohort";const r=t.PCBySubcohort[n];if(!r.termId)throw"termId missing from a subcohort of PCBySubcohort";r.pcs=new Map;for(let n=1;n<=t.PCcount;n++){const t=r.termId+n,s=e.q.termjsonByOneid(t);if(!s)throw"a PC term is not found in termdb";const o=e.q.getAllValues4term(t);if(!o||!o.size)throw"no sample PC values are retrieved by restrictAncestries.PCBySubcohort.<>.termId";r.pcs.set(s.name,o)}}}}}(t),await(0,ks.wz)(e),await(0,qs.te)(e),"minTimeSinceDx"in t){if(!Number.isFinite(t.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(t.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in t){if(!Number.isFinite(t.ageEndOffset))throw"termdb.ageEndOffset not number";if(t.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(t.convertSampleId){if(!t.convertSampleId.gdcapi)throw"unknown implementation of tdb.convertSampleId";Pn.Ak(t,e)}if(await async function(e){if(!e.cohort?.cumburden)return;e.cohort.cumburden.files;const t=e.cohort.cumburden.files;for(const e of["fit","surv","sample"]){const n=t[e];if(!n)throw`missing ds.cohort.burden.files.${e}`;const s=(0,x.spawnSync)(r().Rscript,["-e",`load('${r().tpmasterdir}/${n}')`],{encoding:"utf-8"});if(s?.status||s?.stderr)throw console.log(s),`error with ds.cohort.cumburden.files.${e}`}}(e),e.cohort?.db?.connection){e.sampleName2Id=new Map,e.sampleId2Name=new Map;const t="SELECT * FROM sampleidmap",n=e.cohort.db.connection.prepare(t).all();for(const t of n)e.sampleId2Name.set(t.id,t.name),e.sampleName2Id.set(t.name,t.id);e.getSampleIdMap=t=>{const n={};for(const s in t)n[sampleId]=e.sampleId2Name.get(+sampleId);return n}}if(e.cohort.mutationset){const{mayGetGeneVariantData:t,getTermTypes:s,mayGetMatchingGeneNames:r}=n(7833);e.mayGetGeneVariantData=t,e.getTermTypes=s,e.mayGetMatchingGeneNames=r}}function Es(e,t){const n=[];if(e.filterObj&&n.push(e.filterObj),e.tid2value&&n.push((0,js.w)(e.tid2value,t)),0!=n.length)return 1==n.length?n[0]:(0,ys.xH)(n)}function Rs(e,t,n){if(!t)return;let s;if(e?.cohort?.termdb){for(const e of t){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer sample id from "+n;e.name=t}s=", all integer IDs"}console.log(t.length,"samples from "+n+" of "+e.label+s)}async function Fs(e,t){const n=e.queries.snvindel.byrange;if(n._tk.file)await F._H(n._tk,t,!0);else if(n._tk.chr2files){let e;for(const s in n._tk.chr2files){if("chr17"!=s)continue;const r=n._tk.chr2files[s];try{await F._H(r,t,!0);const o=JSON.stringify(r.samples);if(e){if(o!=e)throw"Different samples found in bcf file of "+s}else e=o,n._tk.samples=r.samples,n._tk.format=r.format,n._tk.info=r.info,n._tk.nochr=r.nochr}catch(e){console.log("missing file ignored:",r.file)}}}if(n._tk?.samples.length){if(!n._tk.format)throw"bcf file has samples but no FORMAT"}else if(n._tk.format)throw"bcf file has FORMAT but no samples";if(n._tk.format){for(const e in n._tk.format)"GT"==e&&(n._tk.format[e].isGT=!0);if(e.queries.snvindel.format4filters){if(!Array.isArray(e.queries.snvindel.format4filters))throw"snvindel.format4filters[] is not array";for(const t of e.queries.snvindel.format4filters)n._tk.format[t]&&(n._tk.format[t].isFilter=!0);delete e.queries.snvindel.format4filters}}if(n._tk.info){if(n.infoFields){for(const e of n.infoFields){if(!e.key)throw".key missing from one of snvindel.byrange.infoFields[]";e.name||(e.name=e.key);const t=n._tk.info[e.key];if(!t)throw"invalid key from one of snvindel.byrange.infoFields[]";t.categories=e.categories,t.name=e.name,t.separator=e.separator}delete n.infoFields}if(e.queries.snvindel.infoUrl){for(const t of e.queries.snvindel.infoUrl){const e=n._tk.info[t.key];if(!e)throw"invalid key from one of snvindel.infoUrl[]";e.urlBase=t.base}delete e.queries.snvindel.infoUrl}}return e.queries.snvindel.info=n._tk.info,e.queries.snvindel.format=n._tk.format,async t=>{if(!Array.isArray(t.rglst))throw"q.rglst[] is not array";if(0==t.rglst.length)throw"q.rglst[] blank array";const s=$s(t);let r;if(n._tk.chr2files){const e=n._tk.chr2files[t.rglst[0].chr];if(!e)throw"unknown chr for chr2files";r=e.file}else r=n._tk.file||n._tk.url;const o=["query",r,"-r",t.rglst.map((e=>(n._tk.nochr?e.chr.replace("chr",""):e.chr)+":"+e.start+"-"+(e.stop+1))).join(","),"-f","%ID\t%CHROM\t%POS\t%REF\t%ALT\t%INFO\t%FORMAT\n"],i=await(0,js.T)(t,n._tk.samples,e);if(i){if(0==i.size)return[];o.push("-s",[...i].join(","))}t.variantFilter&&(0,xs.u)(t.variantFilter,o);const a=[];return await F.UE({isbcf:!0,args:o,dir:n._tk.dir,callback:r=>{const o=r.split("\t"),l=o[0],c=o[1],f=Number(o[2]),u=o[3],d=o[4].split(","),p=o[5],m={pos:f-1};(0,gs.H)(n._tk,u,d,m,p,l,t.isoform);for(const r of m.mlst)t.hiddenmclass&&t.hiddenmclass.has(r.class)||Ds(r,t)||m.mlst.length>1&&t.variantFilter?.lst&&Ls(r,t)||(r.chr=(n._tk.nochr?"chr":"")+c,r.ssm_id=[r.chr,r.pos,r.ref,r.alt].join(hs.dq),n._tk?.samples?.length&&(Ps(n,r,o,t.addFormatValues,e,i,s),!r.samples)||a.push(r))}}),a}}function $s(e){const t=e.formatFilter||{};return"format"==e.skewerRim?.type&&e.skewerRim.hiddenvalues?.size&&(t[e.skewerRim.formatKey]=e.skewerRim.hiddenvalues),Object.keys(t).length?t:void 0}function Ds(e,t){if(!t.infoFilter)return!1;for(const n in t.infoFilter){const s=e.info[n];if(s)if(Array.isArray(s)){for(const e of t.infoFilter[n])if(s.includes(e))return!0}else if(t.infoFilter[n].includes(s))return!0}return!1}function Ls(e,t){for(const n of t.variantFilter.lst){const t=e.info[n.tvs.term.id];if(null==t)return!0;if("integer"==n.tvs.term.type||"float"==n.tvs.term.type){const e=Number(t);if(Number.isNaN(e))return!0;const s=n.tvs.ranges?.[0];if(s){if("start"in s)if(s.startinclusive){if(e<s.start)return!0}else if(e<=s.start)return!0;if("stop"in s)if(s.stopinclusive){if(e>s.stop)return!0}else if(e>=s.stop)return!0}}}return!1}function Ps(e,t,n,s,r,o,i){if(!n[6]||"."==n[6])return;const a=[];for(const t of n[6].split(":")){const n=e._tk.format[t];if(!n)throw"invalid format field: "+n;a.push(n)}const l=[];let c=e._tk.samples;o&&(c=[...o].map((e=>({name:e}))));for(const[e,t]of c.entries()){const r=n[e+7];if(!r||"."==r)continue;const o=Gs(r.split(":"),a,t,s);if(o){if(i){let e=!1;for(const t in i){const n=t in o.formatK2v?o.formatK2v[t]:Ts;if(i[t].has(n)){e=!0;break}}if(e)continue}l.push(o)}}l.length&&(t.samples=l)}function Gs(e,t,n,s){const r={};for(const[n,s]of t.entries()){const t=e[n];if(t&&"."!=t)if(s.isGT){if("./."==t||".|."==t)continue;r.GT=t}else r[s.ID]=t}if(0==Object.keys(r).length)return null;const o={sample_id:n.name};return s&&(o.formatK2v=r),o}function zs(e,t,n,s=1){s=Number(s);const r=200,o=20;let i=0;for(const e in t.majorchr)i+=t.majorchr[e];const a=800/i,l={};let c=0;const f=[];for(const e in t.majorchr){const n=t.majorchr[e];l[e]=(0,rs.Z)().domain([0,n]).range([a*c,a*(c+n)]),c+=n,f.push({chr:e,chrLen:n,xStart:a*(c-n),xStop:a*c})}const u=(0,rs.Z)().domain([n.min,n.max]).range([r,0]),d=(0,S.createCanvas)(890*s,240*s),p=d.getContext("2d");s>1&&p.scale(s,s),g(n.max),g(0),g(n.min);const m=I().createInterface({input:h().createReadStream(e)});return new Promise(((e,s)=>{m.on("line",(e=>{const t=e.split("\t"),s=t[0];if(!s)return;if(!l[s])return;const r=Number(t[1]);if(!Number.isInteger(r))return;const i=Number(t[2]);if(!Number.isFinite(i))return;if(i<n.min||i>n.max)return;p.fillStyle=i>0?n.positiveColor:n.negativeColor;const a=l[s](r),c=o+u(i);p.fillRect(70+a,c,1,1)})),m.on("close",(()=>{!function(){p.strokeStyle="black",p.beginPath();{const e=220-u(0);p.moveTo(70,e),p.lineTo(870,e),p.stroke()}let e=!0;p.fillStyle="black",p.font="12px Arial",p.textAlign="center";for(const n in l){if(p.fillText(n.replace("chr",""),70+l[n](t.majorchr[n]/2),234),e){e=!1;continue}const s=Math.floor(70+l[n](0))+.5;p.moveTo(s,o),p.lineTo(s,220),p.stroke()}p.closePath()}(),e({src:d.toDataURL(),canvasWidth:890,canvasHeight:240,xoff:70,chrLst:f})}))}));function g(e){p.fillStyle="black",p.font="12px Arial",p.textAlign="right";const t=o+u(e);p.fillText(e,64,t+5),p.strokeStyle="black",p.beginPath(),p.moveTo(66,t),p.lineTo(70,t),p.stroke(),p.closePath()}}function Bs(e,t,n,s,r,o){for(const i of t.yesSamples){if(o&&!o.has(i))continue;n.has(i)||n.set(i,{sample:i});const t=n.get(i);s in t||(t[s]={key:s,values:[],label:s}),r?t[s].values.some((t=>t.dt==e&&t.origin==r))||t[s].values.push({dt:Number.parseInt(e),class:"WT",_SAMPLEID_:i,origin:r}):t[s].values.some((t=>t.dt==e))||t[s].values.push({dt:Number.parseInt(e),class:"WT",_SAMPLEID_:i})}for(const i of t.noSamples){if(o&&!o.has(i))continue;n.has(i)||n.set(i,{sample:i});const t=n.get(i);s in t||(t[s]={key:s,values:[],label:s}),r?t[s].values.some((t=>t.dt==e&&t.origin==r))||t[s].values.push({dt:Number.parseInt(e),class:"Blank",_SAMPLEID_:i,origin:r}):t[s].values.some((t=>t.dt==e))||t[s].values.push({dt:Number.parseInt(e),class:"Blank",_SAMPLEID_:i})}}async function Us(e,t){if(e.chr&&Number.isInteger(e.start)&&Number.isInteger(e.stop))return;if(!e.name)throw"both term.name and term.chr/start/stop missing";const n=t.genedb.getjsonbyname.all(e.name);if(0==n.length)throw"unknown gene name";const s=n.find((e=>e.isdefault))||n[0],r=JSON.parse(s.genemodel);if(!r.chr||!Number.isInteger(r.start)||!Number.isInteger(r.stop))throw"invalid chr/start/stop from returned gm";return e.chr=r.chr,e.start=r.start,e.stop=r.stop,r.isoform}async function Js(e,t,n,s){const r={addFormatValues:!0,filter0:s.filter0,filterObj:s.filter,sessionid:s.sessionid,gdcUseCaseuuid:!0};if(e.queries.snvindel.byisoform)return await async function(e,t){if(e.isoform&&"string"==typeof e.isoform)return;if(!e.name)throw"both term.name and term.isoform";const n=t.genedb.getjsonbyname.all(e.name);if(0==n.length)return;const s=n.find((e=>e.isdefault))||n[0],r=JSON.parse(s.genemodel);if(!r.isoform)throw"isoform missing from returned gm";e.isoform=r.isoform}(t,n),t.isoform?(r.isoform=t.isoform,await e.queries.snvindel.byisoform.get(r)):[];if(e.queries.snvindel.byrange)return r.isoform=await Us(t,n),r.rglst=[t],await e.queries.snvindel.byrange.get(r);throw"unknown queries.snvindel method"}function Hs(e,t){t.yesSamples=new Set,t.noSamples=new Set;const n=`SELECT sample, value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = '${t.term_id}'`,s=e.cohort.db.connection.prepare(n).all();for(const e of s)t.yes.value.includes(e.value)?t.yesSamples.add(e.sample):t.no.value.includes(e.value)&&t.noSamples.add(e.sample)}function Ws(e,t,n){if(t.skewerRim){if("format"!=t.skewerRim.type)throw"unknown skewerRim.type";e.rim1count=0;for(const n of e.samples)n.formatK2v?.[t.skewerRim.formatKey]==t.skewerRim.rim1value&&e.rim1count++}}function Vs(e,t){if(t.queries.snvindel?.format)for(const n in t.queries.snvindel.format)if(t.queries.snvindel.format[n].isFilter){e.formatK2count||(e.formatK2count={}),e.formatK2count[n]||(e.formatK2count[n]={v2c:{},unannotatedCount:0});for(const t of e.samples){const s=t.formatK2v?.[n];null==s?e.formatK2count[n].unannotatedCount++:e.formatK2count[n].v2c[s]=1+(e.formatK2count[n].v2c[s]||0)}}}function Zs(e,t){if(e.startunbounded){if(e.stopunbounded)throw"both start & stop are unbounded from "+t;if(!Number.isFinite(e.stop))throw".stop undefined when start is unbounded from "+t}else if(e.stopunbounded){if(!Number.isFinite(e.start))throw".start undefined when stop is unbounded from "+t}else{if(!Number.isFinite(e.start))throw".start undefined when start is not unbounded from "+t;if(!Number.isFinite(e.stop))throw".stop undefined when stop is not unbounded from "+t;if(e.start>=e.stop)throw".start is not lower than stop from "+t}}const Ks="Ancestry_PC_";async function Xs(e,t=null,s=null){if(!e.cohort.termdb)throw"cohort.termdb missing when cohort.db is used";await async function(e){if(e.phewas){if(e.phewas.samplefilter4termtype&&e.phewas.samplefilter4termtype.condition&&!e.phewas.samplefilter4termtype.condition.filter)throw"filter{} missing from tdb.phewas.samplefilter4termtype.condition";if(e.phewas.comparison_groups){if(!Array.isArray(e.phewas.comparison_groups))throw"tdb.phewas.comparison_groups is not array";if(0==e.phewas.comparison_groups.length)throw"tdb.phewas.comparison_groups[] cannot be empty"}}if(e.selectCohort){if(!e.selectCohort.term)throw"term{} missing from termdb.selectCohort";if(!e.selectCohort.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof e.selectCohort.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=e.selectCohort.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';if(!e.selectCohort.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(e.selectCohort.values))throw"termdb.selectCohort.values is not array";if(0==e.selectCohort.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const t of e.selectCohort.values){if(!t.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(t.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==t.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}if(e.restrictAncestries){if(!Array.isArray(e.restrictAncestries)||0==e.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const t of e.restrictAncestries){if(!t.name)throw"name missing from one of restrictAncestries";if("object"!=typeof t.tvs)throw".tvs{} missing from one of restrictAncestries";if(!Number.isInteger(t.PCcount))throw"PCcount is not integer";if(t.PCfile)t.pcs=await Qs(t.PCfile,t.PCcount);else if(t.PCfileBySubcohort)for(const e in t.PCfileBySubcohort){const n=t.PCfileBySubcohort[e];if(!n.file)throw".file missing for a subcohort in PCfileBySubcohort";n.pcs=await Qs(n.file,t.PCcount)}}}}(e.cohort.termdb),await async function(e){if("scatterplots"in e)for(const t of e.scatterplots.plots){const e=y().join(r().tpmasterdir,t.file);await F.Ic(e)}}(e.cohort),(0,vs.JV)(e),function(e){e.sampleName2Id=new Map,e.sampleId2Name=new Map;const t="SELECT * FROM sampleidmap",n=e.cohort.db.connection.prepare(t).all();for(const t of n)e.sampleId2Name.set(t.id,t.name),e.sampleName2Id.set(t.name,t.id);e.getSampleIdMap=t=>{const n={};for(const s in t)n[s]=e.sampleId2Name.get(+s);return n}}(e);const{mayGetGeneVariantData:o,getTermTypes:i,mayGetMatchingGeneNames:a}=n(7833);e.mayGetGeneVariantData=o,e.getTermTypes=i,e.mayGetMatchingGeneNames=a,e.cohort?.db?.refresh&&t&&_s(e,t,s)}async function Ys(e,t){if(!e.track)throw"no mds2 track; missing ds.track{}";const n=e.track;n.name||(n.name=e.label),function(e){if(!e.populations)return;if(!Array.isArray(e.populations))throw"populations should be array";for(const t of e.populations){if(!t.key)throw"key missing from a population";if(t.label||(t.label=t.key),!Array.isArray(t.sets))throw".sets is not an array in population: "+t.key;for(const e of t.sets){if(!e.infokey_AC)throw"infokey_AC missing from a set of population: "+t.key;if(!e.infokey_AN)throw"infokey_AN missing from a set of population: "+t.key;if(t.termfilter&&!e.termfilter_value)throw"termfilter_value missing from a set of population where termfilter is set: "+t.key}}}(n),await async function(e,t,n){if(!e)return;if(!e.chr2bcffile)throw"vcftk.chr2bcffile is missing";{if("object"!=typeof e.chr2bcffile)throw"chr2bcffile not an object";for(const t in e.chr2bcffile)e.chr2bcffile[t]=y().join(r().tpmasterdir,e.chr2bcffile[t]);const n={file:e.chr2bcffile[t.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await F._H(n,t,!0),e.info=n.info,e.format=n.format,e.samples=n.samples,e.nochr=n.nochr}if(e.AD&&e.AD.chr2bcffile){if("object"!=typeof e.AD.chr2bcffile)throw"AD.chr2bcffile not an object";for(const t in e.AD.chr2bcffile)e.AD.chr2bcffile[t]=y().join(r().tpmasterdir,e.AD.chr2bcffile[t]);const s={file:e.AD.chr2bcffile[t.defaultcoord.chr]};if(!s.file)throw"default chr missing from AD.chr2bcffile";await F._H(s,t,!0),e.AD.info=s.info,e.AD.format=s.format,e.AD.samples=s.samples,e.AD.nochr=s.nochr,console.log(n.label+" vcf: AD: "+e.AD.samples.length+" samples");for(const t of e.AD.samples){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer vcf sample: "+t.name;t.name=e}}if(e.samples){for(const t of e.samples){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer vcf sample: "+t.name;t.name=e}console.log(n.label+" vcf: "+e.samples.length+" samples")}else console.log(n.label+" vcf: no samples");if(e.numerical_axis&&e.numerical_axis.info_keys){if(!Array.isArray(e.numerical_axis.info_keys))throw"numerical_axis.info_keys should be an array";for(const t of e.numerical_axis.info_keys){const n=e.info[t.key];if(!n)throw'INFO field "'+t.key+'" not found for numerical_axis';if("Float"!=n.Type&&"Integer"!=n.Type)throw'INFO field "'+t.key+'" from numerical_axis not of integer or float type';if("1"!=n.Number&&"A"!=n.Number)throw'for numerical axis, INFO field "'+t.key+'" only allows to be Number=1 or Number=A'}}if(e.plot_mafcov){if(!e.AD)throw".plot_mafcov enabled but .AD{} missing from vcf";if(!e.AD.samples)throw".plot_mafcov enabled but no samples from vcf";if(!e.AD.format)throw".plot_mafcov enabled but no FORMAT fields from vcf";if(!e.AD.format.AD)throw".plot_mafcov enabled but the AD FORMAT field is missing";if("R"!=e.AD.format.AD.Number)throw"AD FORMAT field Number=R is not true";if("Integer"!=e.AD.format.AD.Type)throw"AD FORMAT field Type=Integer is not true";if(e.plot_mafcov.overlay_term){if(!n.cohort)throw"ds.cohort missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb)throw"ds.cohort.termdb missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb.q)throw"ERR: termdb.q{} missing while trying to access termdb helper functions";if(!n.cohort.termdb.q.termjsonByOneid)throw"ERR: q.termjsonByOneid missing";const t=n.cohort.termdb.q.termjsonByOneid(e.plot_mafcov.overlay_term);if(!t)throw'unknown term id "'+e.plot_mafcov.overlay_term+'" from vcftk.plot_mafcov.overlay_term';e.plot_mafcov.overlay_term=t}}if(e.termdb_bygenotype){if(!e.samples)throw".termdb_bygenotype enabled but no samples from vcf";if(!e.format)throw".termdb_bygenotype enabled but no FORMAT fields from vcf";if(!e.format.GT)throw".termdb_bygenotype enabled but the GT FORMAT field is missing";if(!n.cohort)throw"termdb_bygenotype but ds.cohort missing";if(!n.cohort.termdb)throw"termdb_bygenotype but ds.cohort.termdb missing";if(e.termdb_bygenotype.getAF){if(!e.termdb_bygenotype.termid_sex)throw"termid_sex missing for getAF at termdb_bygenotype";if(!e.termdb_bygenotype.value_male)throw"value_male missing for getAF at termdb_bygenotype";const t=n.cohort.termdb.q.getSample2value(e.termdb_bygenotype.termid_sex);e.termdb_bygenotype.male_samples=new Set;for(const n of t)n.value==e.termdb_bygenotype.value_male&&e.termdb_bygenotype.male_samples.add(n.sample);if(!e.termdb_bygenotype.sex_chrs)throw"sex_chrs missing for getAF at termdb_bygenotype";if(!Array.isArray(e.termdb_bygenotype.sex_chrs))throw"sex_chrs is not array";e.termdb_bygenotype.sex_chrs=new Set(e.termdb_bygenotype.sex_chrs)}}if(e.samples){e.sample2arrayidx=new Map;for(const[t,n]of e.samples.entries())e.sample2arrayidx.set(n.name,t)}}(n.vcf,t,e),function(e){if(!e.info_fields)return;if(!Array.isArray(e.info_fields))throw"tk.info_fields is not array";for(const t of e.info_fields){if(!t.key)throw".key missing from one of tk.info_fields[]";if(e.vcf&&e.vcf.info&&!e.vcf.info[t.key])throw`info field ${t.key} missing from tk.vcf.info{}`;if(t.label||(t.label=t.key),t.iscategorical){if(!Array.isArray(t.values))throw".values[] not an array of categorical INFO field: "+t.key;for(const e of t.values){if(!e.key)throw"key missing from a value of categorical INFO: "+t.key;e.label||(e.label=e.key)}}else if(t.isfloat||t.isinteger){if(!t.range)throw".range{} missing from a numerical INFO: "+t.key;Zs(t.range,"tk.info_fields[]")}else if(!t.isflag)throw"tk.info_fields unknown type: "+t.key}}(n),await async function(e,t,n){if(!e)return;if(!Array.isArray(e.tracks))throw"ld.tracks[] not an array";if(0==e.tracks.length)throw"ld.tracks[] is empty array";for(const n of e.tracks){if(!n.name)throw".name missing from a ld track";if(!Number.isInteger(n.viewrangelimit))throw'viewrangelimit missing from ld track "'+n.name+'"';if(n.file)n.file.startsWith(r().tpmasterdir)||(n.file=y().join(r().tpmasterdir,n.file)),await F.LC(n.file),n.nochr=await F.Jy(n.file,null,t),console.log(n.file+": "+(n.nochr?"no chr":"has chr"));else if(!n.chr2file)throw"ld tk has no file or chr2file"}}(n.ld,t),await async function(e,t){if(!e)return}(n.svcnv,0),function(e){const t=new Set;if(e.vcf&&e.vcf.samples)for(const n of e.vcf.samples)t.add(n.name);e.svcnv;t.size&&(e.samples=[...t])}(n),n.samples&&console.log(e.label+": mds2: "+n.samples.length+" samples")}async function Qs(e,t){const n=new Map;for(let e=1;e<=t;e++)n.set(Ks+e,new Map);let s=0;for(const o of(await F.b5(y().join(r().tpmasterdir,e))).trim().split("\n")){s++;const e=o.split("\t"),r=Number(e[0]);if(!Number.isInteger(r))throw"non-integer sample id from a line of restrictAncestries pc file";for(let s=1;s<=t;s++){const t=Ks+s,o=Number(e[s]);if(Number.isNaN(o))throw"non-numeric PC value from restrictAncestries file";n.get(t).set(r,o)}}return console.log(s,"samples loaded from "+e),Object.freeze(n)}var er=n(9157);const tr=n(334),nr="%CHROM\t%POS\t%ID\t%REF\t%ALT\t%QUAL\t%FILTER\t%INFO";async function sr(e,t,n,s){if(!e.rglst)throw".rglst[] missing";const r=n.track.vcf;if(!r)throw"ds.track.vcf missing";const o={info:r.info,format:r.format,samples:r.samples};await async function(e,t,n){if(e.querymode={},e.AFtest){if(n.iscustom)throw"custom track does not support AFtest";for(const t of e.AFtest.groups)if(!t.is_infofield)if(t.is_termdb)t.columnidx=await rr(t.filter,n);else{if(!t.is_population)throw"Cannot set query mode: unknown group type";{if(!n.track.populations)throw"ds.track.populations missing";const s=n.track.populations.find((e=>e.key==t.key));if(!s)throw"unknown population key: "+t.key;if(t.population=JSON.parse(JSON.stringify(s)),e.AFtest.termfilter&&e.AFtest.termfilter[0].term.id==t.population.termfilter){const n=t.population.sets.find((t=>t.termfilter_value==e.AFtest.termfilter[0].values[0].key));if(!n)throw"no matching set found for a termfilter from a population";t.population.sets=[n]}}}if(e.AFtest.testby_fisher&&e.AFtest.groups.find((e=>e.is_infofield)))throw"cannot do fisher test for an INFO field";{const t=e.AFtest.groups.find((e=>e.is_population));if(t&&t.adjust_race){const s=e.AFtest.groups.find((e=>e.is_termdb));if(!s)throw"cannot adjust race: termdb group missing";s.pop2average=await async function(e,t,n,s){const r=new Map;let o=0;for(const t of e){const e={infokey_AC:t.infokey_AC,infokey_AN:t.infokey_AN,average:0},s=await bs.J4({ds:n,key:t.key});for(const t of s){if(!n.track.vcf.sample2arrayidx.has(t.sample))continue;const s=Number(t.value);Number.isFinite(s)&&(e.average+=s,o+=s)}r.set(t.key,e)}for(const[e,t]of r)t.average/=o;return r}(t.population.sets,s.columnidx,n)}}return void(e.querymode.range_AFtest=!0)}e.querymode.range_variantonly=!0}(e,0,n),function(e,t){if(t.querymode.range_variantonly||t.querymode.range_AFtest){delete e.samples;for(const e of t.rglst)e.variants=[]}t.bcfformat=nr,t.exportgenotype||t.querymode.range_AFtest?t.bcfformat+="\t%FORMAT\n":t.querymode.range_variantonly&&(t.querymode.slicecolumnindex||(t.bcfformat+="\\n"))}(o,e),e.exportgenotype&&(s.mlst=[]),function(e,t){const n=(s=e.rglst[0],s.usegm_isoform?{gmmode:"protein",usegm:{isoform:s.usegm_isoform}}:{});var s;e.m_is_filtered=s=>{let r=!1;if(e.info_fields)for(const n of e.info_fields){const e=t.info_fields[n.key];let o;if(s.info&&(o=s.info[n.key]),null==o&&s.altinfo&&(o=s.altinfo[n.key]),n.iscategorical)null==o?(e.unannotated_count=1+(e.unannotated_count||0),n.unannotated_ishidden&&(r=!0)):(e.value2count[o]=1+(e.value2count[o]||0),n.hiddenvalues[o]&&(r=!0));else if(n.isnumerical)null==o&&null!=n.missing_value&&(o=n.missing_value),n.range.startunbounded||(n.range.startinclusive?o<n.range.start&&(r=!0):o<=n.range.start&&(r=!0)),n.range.stopunbounded||(n.range.stopinclusive?o>n.range.stop&&(r=!0):o>=n.range.stop&&(r=!0)),r&&e.filteredcount++;else{if(!n.isflag)throw"unknown info type";o?e.count_yes++:e.count_no++,(n.remove_yes&&o||n.remove_no&&!o)&&(r=!0)}}return!!r||($.vcfcopymclass(s,n),t.mclass2count[s.class]=(t.mclass2count[s.class]||0)+1,e.hidden_mclass&&e.hidden_mclass.has(s.class)&&(r=!0),r)}}(e,s);for(const t of e.rglst){if(r.viewrangeupperlimit&&t.stop-t.start>=r.viewrangeupperlimit){t.rangetoobig="Zoom in under "+$.bplen(r.viewrangeupperlimit)+" to view VCF data";continue}const n=(r.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop,s=r.chr2bcffile[t.chr];if(!s)throw"chr not found in chr2bcffile";await F.UE({isbcf:!0,args:["query",s,"-r",n,"-f",e.bcfformat],dir:r.dir,callback:i(t)})}function i(t){return n=>{if(e.exportgenotype){const t=n.split("\t"),[r,i,a]=D.S(t.slice(0,8).join("\t"),o);for(const n of i){if(e.m_is_filtered(n))continue;const r=[n.chr+"."+(n.pos+1)+"."+n.ref+"."+n.alt,n.name||""];for(let e=9;e<t.length;e++){const s=t[e].split(":",1)[0];if("."==s){r.push(".");continue}const o=s.split(-1==s.indexOf("/")?"|":"/");r.push(("0"==o[0]?n.ref:n.alt)+("0"==o[1]?n.ref:n.alt))}s.mlst.push(r.join("\t"))}return}let i;if(e.querymode.range_variantonly)if(e.querymode.slicecolumnindex);else{const[t,s,r]=D.S(n,o);i=[];for(const t of s)e.m_is_filtered(t)||i.push(t)}else e.querymode.range_AFtest&&(i=function(e,t,n,s){const r=e.split("\t"),[o,i,a]=D.S(r.slice(0,8).join("\t"),n),l=i.filter((e=>!t.m_is_filtered(e)));if(0==l.length)return;const c=[r[3],...r[4].split(",")],f=[];for(const e of l){const n=ir(r,e,c,t);if(or(n)){if(f.push(e),t.AFtest.testby_AFdiff){for(const e of n)if(e.is_infofield)e.v=e.infofieldvalue;else{if(!e.is_termdb&&!e.is_population)throw"unknown group 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t=Pr[e],n={species:t.species,name:e,hasSNP:!!t.snp,hasIdeogram:t.genedb.hasIdeogram,fimo_motif:!!t.fimo_motif,blat:!!t.blat,geneset:t.geneset,defaultcoord:t.defaultcoord,isdefault:t.isdefault,majorchr:t.majorchr,majorchrorder:t.majorchrorder,minorchr:t.minorchr,tracks:t.tracks,hicenzymefragment:t.hicenzymefragment,datasets:{}};if(t.termdbs){n.termdbs={};for(const e in t.termdbs)n.termdbs[e]={label:t.termdbs[e].label}}for(const e in t.datasets){const s=t.datasets[e];s.isMds3?n.datasets[s.label]={isMds3:!0,noHandleOnClient:s.noHandleOnClient,label:s.label}:s.isMds?n.datasets[s.label]={isMds:!0,mdsIsUninitiated:!0,noHandleOnClient:s.noHandleOnClient,label:s.label}:n.datasets[s.label]={isofficial:!0,legacyDsIsUninitiated:!0,noHandleOnClient:s.noHandleOnClient,label:s.label}}if(t.hicdomain){n.hicdomain={groups:{}};for(const e in t.hicdomain.groups){const s=t.hicdomain.groups[e];n.hicdomain.groups[e]={name:s.name,reference:s.reference,sets:{}};for(const t in s.sets)n.hicdomain.groups[e].sets[t]={name:s.sets[t].name,longname:s.sets[t].longname}}}return n}function Xr(e){const t={noHandleOnClient:e.noHandleOnClient,sampleselectable:e.sampleselectable,label:e.label,dsinfo:e.dsinfo,stratify:e.stratify,cohort:e.cohort,vcfinfofilter:e.vcfinfofilter,info2table:e.info2table,info2singletable:e.info2singletable,url4variant:e.url4variant,itemlabelname:e.itemlabelname};if(e.snvindel_attributes){t.snvindel_attributes=[];for(const n of e.snvindel_attributes){const e={};for(const t in n)if("lst"==t){e.lst=[];for(const t of n.lst){const n={};for(const e in t)n[e]=t[e];e.lst.push(n)}}else e[t]=n[t];t.snvindel_attributes.push(e)}}e.snvindel_legend&&(t.snvindel_legend=e.snvindel_legend);const n={};let s=!1;for(const t of e.queries)t.vcf&&(s=!0,n[t.vcf.vcfid]=t.vcf);return s&&(t.id2vcf=n),t}function Yr(e){const t={isMds:!0,noHandleOnClient:e.noHandleOnClient,label:e.label,version:e.version,annotationsampleset2matrix:e.annotationsampleset2matrix,mutationAttribute:e.mutationAttribute,locusAttribute:e.locusAttribute,alleleAttribute:e.alleleAttribute,hide_genotypedownload:e.hide_genotypedownload,hide_phewas:e.hide_phewas,sample2bam:e.sample2bam};if(e.queries&&(t.queries={}),e.track&&(t.track=function(e){const t=e.track,n={name:t.name,info_fields:t.info_fields,sample_termfilter:t.sample_termfilter};return t.vcf&&(n.vcf={numerical_axis:t.vcf.numerical_axis,format:t.vcf.format,info:t.vcf.info,check_pecanpie:t.vcf.check_pecanpie},t.vcf.plot_mafcov&&(n.vcf.plot_mafcov={},e.cohort&&e.cohort.termdb&&(n.vcf.plot_mafcov.overlay_term=t.vcf.plot_mafcov.overlay_term||{})),t.vcf.termdb_bygenotype&&(n.vcf.termdb_bygenotype=!0),t.populations&&(n.populations=t.populations)),t.ld&&(n.ld={tracks:t.ld.tracks.map((e=>({name:e.name,shown:e.shown}))),overlay:t.ld.overlay}),n}(e)),e.singlesamplemutationjson&&(t.singlesamplemutationjson=1),e.gene2mutcount&&(t.gene2mutcount=!0,t.mutCountType=e.gene2mutcount.mutationTypes),e.assayAvailability&&(t.assayAvailability=1),e.cohort&&e.cohort.sampleAttribute){const n={};for(const t in e.cohort.sampleAttribute.attributes){const s=e.cohort.sampleAttribute.attributes[t];s.clientnoshow||(n[t]=s)}t.sampleAttribute={attributes:n}}if(e.cohort){if(e.cohort.termdb&&(t.termdb={selectCohort:e.cohort.termdb.selectCohort}),e.cohort.attributes&&e.cohort.attributes.defaulthidden&&(t.cohortHiddenAttr=e.cohort.attributes.defaulthidden),e.cohort.survivalplot){t.survivalplot={samplegroupattrlst:e.cohort.survivalplot.samplegroupattrlst,plots:[]};for(const n in e.cohort.survivalplot.plots){const s=e.cohort.survivalplot.plots[n];t.survivalplot.plots.push({key:n,name:s.name,timelabel:s.timelabel})}}if(e.cohort.mutation_signature){const n={};for(const t in e.cohort.mutation_signature.sets){const s=e.cohort.mutation_signature.sets[t];n[t]={name:s.name,signatures:s.signatures}}t.mutation_signature={sets:n}}}for(const n in e.queries){const s=e.queries[n],r={name:s.name,hideforthemoment:s.hideforthemoment};if(s.istrack){if(r.istrack=!0,r.type=s.type,r.isfull=s.isfull,null!=s.nochr&&(r.nochr=s.nochr),s.infoFilter&&(r.infoFilter=s.infoFilter),s.readcountCutoff&&(r.readcountCutoff=s.readcountCutoff),s.valueLabel&&(r.valueLabel=s.valueLabel),s.valueCutoff&&(r.valueCutoff=s.valueCutoff),s.bplengthUpperLimit&&(r.bplengthUpperLimit=s.bplengthUpperLimit),s.segmeanValueCutoff&&(r.segmeanValueCutoff=s.segmeanValueCutoff),s.lohLengthUpperLimit&&(r.lohLengthUpperLimit=s.lohLengthUpperLimit),s.type==$.tkt.mdssvcnv){if(s.groupsamplebyattr&&(r.groupsamplebyattr=s.groupsamplebyattr),r.multihidelabel_fusion=s.multihidelabel_fusion,r.multihidelabel_sv=s.multihidelabel_sv,r.multihidelabel_vcf=s.multihidelabel_vcf,r.showfullmode=s.showfullmode,r.legend_vorigin=s.legend_vorigin,r.no_loh=s.no_loh,s.expressionrank_querykey){const t=e.queries[s.expressionrank_querykey];if(r.checkexpressionrank={querykey:s.expressionrank_querykey,datatype:t.datatype},t.boxplotbysamplegroup&&t.boxplotbysamplegroup.additionals){const e=[];t.boxplotbysamplegroup.attributes&&e.push(t.boxplotbysamplegroup.attributes.map((e=>e.label)).join(", "));for(const n of t.boxplotbysamplegroup.additionals)e.push(n.label);r.checkexpressionrank.boxplotgroupers=e}}if(s.vcf_querykey){r.checkvcf={querykey:s.vcf_querykey,info:e.queries[s.vcf_querykey].info,format:{}};for(const t of e.queries[s.vcf_querykey].tracks)if(t.format)for(const e in t.format)r.checkvcf.format[e]=t.format[e]}}}else{if(!s.isgenenumeric)continue;r.isgenenumeric=!0,r.datatype=s.datatype,r.no_ase=s.no_ase}t.queries[n]=r}return t}async function Qr(e,t){if(!t)throw"invalid genome";if(!t.snp)throw"snp is not configured for this genome";const n=[];if(e.byCoord){if(t.genomicNameRegexp.test(e.chr))throw"invalid chr name";if(!Array.isArray(e.ranges))throw"ranges not an array";for(const s of e.ranges){if(!Number.isInteger(s.start)||!Number.isInteger(s.stop)||s.start<0||s.stop<s.start)throw"invalid start/stop";if(s.stop-s.start>=100)throw"range too big";const r=await F.z5(t.snp.bigbedfile,e.chr,s.start,s.stop);for(const t of r){const s=eo(t);if(e.alleleLst){let t=!1;for(const n of e.alleleLst)if(n&&!s.alleles.includes(n)){t=!0;break}if(t)continue}n.push(s)}}}else{if(!e.byName)throw"unknown query method";if(!Array.isArray(e.lst))throw".lst[] missing";for(const s of e.lst){if(t.genomicNameRegexp.test(s))continue;const e=await F.mr(t.snp.bigbedfile,s);for(const t of e){const e=eo(t);n.push(e)}}}return n}function eo(e){const t=e.split("\t"),n=t[4],s=t[6].split(",").filter(Boolean),r=n+"/"+s.join("/");return{chrom:t[0],chromStart:Number(t[1]),chromEnd:Number(t[2]),name:t[3],observed:r,alleles:[n,...s]}}function to(e,t,n){if(n.query.isoform&&Pr[n.query.genome].genomicNameRegexp.test(n.query.isoform))return;const[s,r]=t.makequery(n.query);if(!s)return;const o=e.newconn.prepare(s).all(r);let i;i=t.tidy?o.map((e=>t.tidy(e))):o;const a={};if(t.isgeneexpression){a.lst=i,a.isgeneexpression=!0,a.config=t.config;for(const t of e.queries)if(t.dsblocktracklst)for(const e of t.dsblocktracklst)e.type==$.tkt.junction&&(a.config.dsjunctiontk=e)}else a.lst=i;return a}function no(e,t){const n=[y().join(r().tpmasterdir,e.vcffile),(e.vcf.nochr?t.query.range.chr.replace("chr",""):t.query.range.chr)+":"+t.query.range.start+"-"+t.query.range.stop];return new Promise(((t,s)=>{const r=(0,x.spawn)(Gr,n),o=[],i=[];r.stdout.on("data",(e=>o.push(e))),r.stderr.on("data",(e=>i.push(e))),r.on("close",(n=>{""!=i.join("").trim()&&s("error querying vcf file");const r=o.join("").trim();t({lines:""==r?[]:r.split("\n"),vcfid:e.vcf.vcfid})}))}))}function so(e){if(!e.genome)return["no genome"];const t=Pr[e.genome];if(!t)return["invalid genome"];if(!t.datasets)return["genome is not equipped with datasets"];if(!e.dslabel)return["dslabel missing"];const n=t.datasets[e.dslabel];if(!n)return["invalid dslabel"];if(!n.queries)return["dataset is not equipped with queries"];if(!e.querykey)return["querykey missing"];const s=n.queries[e.querykey];return s?[null,t,n,s]:["invalid querykey"]}async function ro(e,t,n,s,o,i){const a=await async function(e,t,n,s){const o=e.checkvcf.tracks[0],i={file:o.file,url:o.url,indexURL:o.indexURL,dir:o.dir,nochr:o.nochr,samples:o.samples,info:e.checkvcf.info,format:o.format},a=await yo(i.file?y().join(r().tpmasterdir,i.file):i.url,(i.nochr?t.replace("chr",""):t)+":"+n+"-"+s,i.dir),l=[];for(const e of a||[]){const[t,n,s]=D.S(e,i);for(const e of n)$.basecolor[e.ref]&&$.basecolor[e.alt]&&e.sampledata&&l.push(e)}return l}(o,t,n,s),l=[];for(const e in o.checkrnabam.samples){const n=o.checkrnabam.samples[e];n.hetsnps=[];for(const t of a){const s=ho(t,e,o.checkrnabam);s&&s.dnacount.ishet&&n.hetsnps.push(s)}if(n.url?n.dir=await 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n()}))}))}(s,t),h().unlink(n,(()=>{})),h().unlink(s,(()=>{}))}(l,o.checkrnabam.samples),i.checkrnabam=[];for(const n in o.checkrnabam.samples){const s=o.checkrnabam.samples[n],r=[];for(const[n,i]of e){const e={gene:n,chr:t,start:i.start,stop:i.stop},a=s.hetsnps.filter((e=>e.pos>=i.start&&e.pos<=i.stop)),l=a.filter((e=>!e.rnacount.nocoverage));if(l.length>0){const t=l.reduce(((e,t)=>e+Math.abs(t.rnacount.f-.5)),0);let n=null,s=0;for(const e of l)null!=e.rnacount.pvalue&&(null==n?n=e.rnacount.pvalue:n*=e.rnacount.pvalue,e.rnacount.pvalue<=o.checkrnabam.binompvaluecutoff&&s++);null!=n&&(e.ase={markers:a.filter((e=>e.dnacount.ishet)).length,ase_markers:s,mean_delta:t/l.length,geometricmean:Math.pow(n,1/l.length)})}let c;c=s.pairedend?await io(s,t,i):await oo(s,t,i),e.fpkm=1e9*c/(s.totalreads*i.exonlength),e.snps=a,r.push(e)}r.length&&i.checkrnabam.push({sample:n,genes:r})}}async function oo(e,t,n){const s=["view","-c","-M",e.url||e.file];for(const r of n.exonunion)s.push((e.nochr?t.replace("chr",""):t)+":"+(r[0]+1)+"-"+(r[1]+1));let r;return await F.UE({isbam:!0,args:s,dir:e.dir,callback:e=>r=e}),Number.parseInt(r)}function io(e,t,n){return new Promise(((s,r)=>{const o=["view","-M",e.url||e.file];for(const s of n.exonunion)o.push((e.nochr?t.replace("chr",""):t)+":"+(s[0]+1)+"-"+(s[1]+1));const i=(0,x.spawn)(zr,o,{cwd:e.dir}),a=(0,x.spawn)("cut",["-f1"],{cwd:e.dir}),l=(0,x.spawn)("sort",["-u"],{cwd:e.dir}),c=(0,x.spawn)("wc",["-l"],{cwd:e.dir});i.stdout.pipe(a.stdin),a.stdout.pipe(l.stdin),l.stdout.pipe(c.stdin);const f=[],u=[];c.stdout.on("data",(e=>f.push(e))),c.stderr.on("data",(e=>u.push(e))),c.on("close",(()=>{s(Number.parseInt(f.join("")))}))}))}function ao(e,t,n,s){const r=[];for(const s of t)s.rnacount={nocoverage:1},r.push((e.nochr?n.replace("chr",""):n)+":"+(s.pos+1)+"-"+(s.pos+1));return new Promise(((n,o)=>{const i=(0,x.spawn)(Br,["mpileup","--no-reference","-a","INFO/AD","-d",999999,"-r",r.join(","),"-q",s.rnapileup_q,"-Q",s.rnapileup_Q,e.url||e.file],{cwd:e.dir});I().createInterface({input:i.stdout}).on("line",(e=>{if("#"==e[0])return;const n=mo(e);if(!n)return;const s=t.find((e=>e.pos==n.pos));if(s){const e=n.allele2count[s.ref]||0,t=n.allele2count[s.alt]||0;e+t>0&&(s.rnacount={ref:e,alt:t,f:t/(e+t)})}})),i.on("close",(()=>{n()}))}))}function lo(e,t,n,s,r,o){t.hideLOHwithCNVoverlap&&co(r);const i=[];if(o){const e=new Map;for(const[t,n]of r){const s=o.sample2group.get(t);e.has(s)||e.set(s,[]),e.get(s).push({samplename:t,items:n})}if(s)for(const t of s)if(t.dt!=$.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+t.dt);else for(const n of t.sampledata){const t=o.sample2group.get(n.sampleobj.name);e.has(t)||e.set(t,[]),e.get(t).find((e=>e.samplename==n.sampleobj.name))||e.get(t).push({samplename:n.sampleobj.name,items:[]})}for(const[t,n]of e)i.push({name:t,samples:n})}else if(e.cohort&&e.cohort.annotation&&t.groupsamplebyattr){const n=new Map,o=[];for(const[s,i]of r)fo(s,i,n,o,e,t);if(s)for(const r of s)if(r.dt!=$.dtsnvindel)console.log("unknown dt when grouping samples from vcf data: "+r.dt);else for(const s of r.sampledata)fo(s.sampleobj.name,[],n,o,e,t);for(const e of n.values())if(i.push(e),t.groupsamplebyattr.key2group){const n=t.groupsamplebyattr.key2group.get(e.name);n&&(e.sampletotalnum=n.samples.length)}o.length&&i.push({name:"Unannotated",samples:o});for(const t of i)for(const n of t.samples)e.cohort.annotation[n.samplename]&&(n.sampletype=e.cohort.annotation[n.samplename].sample_type)}else{const e=[];for(const[t,n]of r)e.push({samplename:t,items:n});if(s)for(const t of s)if(t.dt!=$.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+t.dt);else for(const n of t.sampledata){let t=!0;for(const s of e)if(s.samplename==n.sampleobj.name){t=!1;break}t&&e.push({samplename:n.sampleobj.name,items:[]})}e.length&&i.push({samples:e})}return i}function co(e){for(const[t,n]of e){const s=new Map,r=new Map,o=[];for(const e of n)e.dt!=$.dtloh?(e.dt==$.dtcnv&&(r.has(e.chr)||r.set(e.chr,[]),r.get(e.chr).push(e)),o.push(e)):(s.has(e.chr)||s.set(e.chr,[]),s.get(e.chr).push(e));if(0!=s.size){for(const[e,t]of s){const n=r.get(e);if(n)for(const e of t){let t=!0;for(const s of n)if(Math.max(e.start,s.start)<Math.min(e.stop,s.stop)){t=!1;break}t&&o.push(e)}else for(const e of t)o.push(e)}e.set(t,o)}}}function fo(e,t,n,s,r,o){const i=r.cohort.annotation[e];if(!i)return void s.push({samplename:e,items:t});const a=i[o.groupsamplebyattr.attrlst[0].k];if(null==a)return void s.push({samplename:e,items:t});const l=[];for(let e=1;e<o.groupsamplebyattr.attrlst.length;e++){const t=i[o.groupsamplebyattr.attrlst[e].k];if(null==t)break;l.push(t)}l.unshift(a);const 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function(e,t){try{await h().promises.stat(r().tpmasterdir)}catch(e){let n="Error with TP directory ("+e.code+")";const s=r().maintenance||{};if("start"in s&&"stop"in s&&s.tpMessage){const e=+new Date(s.start),t=+new Date(s.stop),r=+new Date;e<=r&&r<=t&&(n=s.tpMessage)}return void t.send({error:n})}const n={};if(e.query&&e.query.genome)n[e.query.genome]=Kr(e.query.genome);else for(const e in Pr)n[e]=Kr(e);let s=!1;for(const e in Pr)Pr[e].blat&&(s=!0);t.send({genomes:n,debugmode:r().debugmode,headermessage:r().headermessage,base_zindex:r().base_zindex,codedate:Rr.A.codedate,launchdate:Rr.A.launchdate,hasblat:s,features:Lr,dsAuth:mr.i.getDsAuth(e),commonOverrides:r().commonOverrides,targetPortal:r().targetPortal,cardsPath:r().cards?.path})})),Jr.get(Hr+"/getDataset",(function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"unknown genome";if(!n.datasets)throw"genomeobj.datasets{} missing";let s;for(const t in n.datasets)if(t.toLowerCase()==e.query.dsname.toLowerCase()){s=n.datasets[t];break}if(!s)throw"invalid dsname";return s.isMds3?t.send({ds:Os(s)}):s.isMds?t.send({ds:Yr(s)}):t.send({ds:Xr(s)})}catch(e){t.send({error:e.message||e})}})),Jr.all(Hr+"/ntseq",(async function(e,t){try{if(!e.query.coord)throw"coord missing";const n=Pr[e.query.genome];if(!n)throw"invalid genome";if(!n.genomefile)throw"no sequence file available";const s=await F.Kf(n,e.query.coord);t.send({seq:s.split("\n").slice(1).join("")})}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Jr.post(Hr+"/pdomain",(function(e,t){try{const n=e.query.genome;if(!n)throw"no genome";const s=Pr[n];if(!s)throw"invalid genome "+n;if(!s.proteindomain)return t.send({lst:[]});if(!Array.isArray(e.query.isoforms))throw"isoforms[] missing";const r=[];for(const t of e.query.isoforms){if(s.genomicNameRegexp.test(t))continue;const e=s.proteindomain.getbyisoform.all(t);r.push({name:t,pdomains:e.map((e=>{const n=JSON.parse(e.data);return n.refseq=t,n}))})}t.send({lst:r})}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Jr.post(Hr+"/tkbedj",function(e){return async(t,n)=>{try{n.send(await async function(e,t){const[n,s,r]=F.ZX(e);if(n)throw n;let o,i,a,l,c;if(e.query.fileIsBigbed=await F.aS(s),e.query.getdata)e.query.getBED;else{if(o=Number(e.query.stackheight),i=Number(e.query.stackspace),a=Number(e.query.regionspace),l=Number(e.query.width),Number.isNaN(o))throw"stackheight is not integer";if(c=Math.max(10,o-2),Number.isNaN(i))throw"stackspace is not integer";if(Number.isNaN(a))throw"regionspace is not integer";if(Number.isNaN(l))throw"width is not a number"}if(e.query.usevalue){if(!e.query.usevalue.key)throw".key missing from .usevalue";if(e.query.usevalue.dropBelowCutoff&&(e.query.usevalue.dropBelowCutoff=Number(e.query.usevalue.dropBelowCutoff),Number.isNaN(e.query.usevalue.dropBelowCutoff)))throw".usevalue.dropBelowCutoff is not number"}if(e.query.bplengthUpperLimit&&(e.query.bplengthUpperLimit=Number(e.query.bplengthUpperLimit),Number.isNaN(e.query.bplengthUpperLimit)))throw"bplengthUpperLimit not number";if(!e.query.rglst)throw"no rglst[]";if(!Array.isArray(e.query.rglst))throw"rglst is not an array";if(0==e.query.rglst.length)throw"empty rglst";for(const t of e.query.rglst)t.reverse?t.scale=e=>Math.ceil(t.width*(t.stop-e)/(t.stop-t.start)):t.scale=e=>Math.ceil(t.width*(e-t.start)/(t.stop-t.start));const f=e.query.color||"#3D7A4B",u=e.query.gmregion||null,d=e.query.isoform,p=e.query.onerow,m=e.query.categories||null,h=e.query.__isgene;let g;!e.query.fileIsBigbed&&r&&(g=await F.d1(s,e.query.indexURL));const y=await async function(e,t,n,s,r){let o;if(s){const i=[];if(e.fileIsBigbed){const n=await F.z5(t,s.chr,s.start,s.stop);for(const t of n){const n=t.split("\t"),s=Bn(n);s.chr=n[0],s.start=Number(n[1]),s.stop=Number(n[2]),s.rglst=[];for(let t=0;t<e.rglst.length;t++){const n=e.rglst[t];Math.max(s.start,n.start)<Math.min(s.stop,n.stop)&&s.rglst.push({idx:t})}0!=s.rglst.length&&i.push(s)}}else await F.UE({args:[t,s.chr+":"+s.start+"-"+s.stop],dir:n,callback:t=>{const n=t.split("\t");let s={};if(e.getBED)s.rest=n.slice(3);else if(n[3])try{s=JSON.parse(n[3])}catch(e){return void(o=t)}if(!s.isoformonly||s.isoformonly==r){s.chr=n[0],s.start=Number(n[1]),s.stop=Number(n[2]),s.rglst=[];for(let t=0;t<e.rglst.length;t++){const n=e.rglst[t];Math.max(s.start,n.start)<Math.min(s.stop,n.stop)&&s.rglst.push({idx:t})}0!=s.rglst.length&&i.push(s)}}});if(o)throw"Line with invalid JSON: "+o;return[i]}const i=[];for(const[s,r]of e.rglst.entries()){const a=[];if(e.fileIsBigbed){const e=await F.z5(t,r.chr,r.start,r.stop);for(const t of e){const e=t.split("\t"),n=Bn(e);n.chr=e[0],n.start=Number(e[1]),n.stop=Number(e[2]),n.rglst=[{idx:s}],a.push(n)}}else await F.UE({args:[t,r.chr+":"+r.start+"-"+r.stop],dir:n,callback:t=>{const n=t.split("\t");let r={};if(e.getBED)r.rest=n.slice(3);else if(n[3])try{r=JSON.parse(n[3])}catch(e){return void(o=t)}r.chr=n[0],r.start=Number(n[1]),r.stop=Number(n[2]),r.rglst=[{idx:s}],a.push(r)}});i.push(a)}if(o)throw"Line with invalid JSON: "+o;return i}(e.query,s,g,u,d);let b;e.query.filterByName&&(b=new Set(e.query.filterByName.split(/[\s\n]/).map((e=>e.trim()))));const v=[];for(const t of y)for(const n of t){if(e.query.usevalue){const t=n[e.query.usevalue.key];if(!Number.isFinite(t))continue;if(e.query.usevalue.dropBelowCutoff&&t<e.query.usevalue.dropBelowCutoff)continue}if(!(e.query.bplengthUpperLimit&&n.stop-n.start>e.query.bplengthUpperLimit)){if(b)if(n.isoform){if(!b.has(n.isoform))continue}else{if(!n.name)continue;if(!b.has(n.name))continue}v.push(n)}}if(e.query.getdata)return{items:v};if(0==v.length){const t=(0,S.createCanvas)(l*e.query.devicePixelRatio,o*e.query.devicePixelRatio),n=t.getContext("2d");return e.query.devicePixelRatio>1&&n.scale(e.query.devicePixelRatio,e.query.devicePixelRatio),n.font=o+"px Arial",n.fillStyle="#aaa",n.textAlign="center",n.textBaseline="middle",n.fillText("No data in view range",l/2,o/2),{src:t.toDataURL(),height:o}}const w=Math.ceil(o/4)-1;if(p||v.length>=Wn){const t=v.length<200,n=(0,S.createCanvas)(l*e.query.devicePixelRatio,o*e.query.devicePixelRatio),s=n.getContext("2d");e.query.devicePixelRatio>1&&s.scale(e.query.devicePixelRatio,e.query.devicePixelRatio);const r=v.length<=200?[]:null;for(const n of v){const i=m&&n.category&&m[n.category]?m[n.category].color:n.color||f;s.fillStyle=i;for(const i of n.rglst){let l=0;for(let t=0;t<i.idx;t++)l+=e.query.rglst[t].width+a;const c=e.query.rglst[i.idx],f=[];n.utr5&&f.push(...n.utr5),n.utr3&&f.push(...n.utr3),!n.exon||n.coding&&0!=n.coding.length||f.push(...n.exon);for(const e of f){const t=Math.max(c.start,e[0]),i=Math.min(c.stop,e[1]),a=l+c.scale(c.reverse?i:t),f=l+c.scale(c.reverse?t:i);s.fillRect(a,w,Math.max(1,f-a),o-2*w),es(r,a,f,1,n)}const u=[];n.exon?n.coding&&n.coding.length>0&&u.push(...n.coding):u.push([n.start,n.stop]);for(const e of u){const i=Math.max(c.start,e[0]),a=Math.min(c.stop,e[1]),f=l+c.scale(c.reverse?a:i),u=l+c.scale(c.reverse?i:a);s.fillRect(f,0,Math.max(1,u-f),o),es(r,f,u,1,n),n.strand&&t&&(s.strokeStyle="white",ts(s,n.strand,f,w,u-f,o-2*w))}}}return{src:n.toDataURL(),height:o,mapisoform:r}}if(e.query.hideItemNames)for(const e of v)delete e.name;let _=null;if(h&&v.length<Vn){_=[];for(const e of v){const t={};for(const n in e)"canvas"!=n&&"rglst"!=n&&(t[n]=e[n]);_.push(t)}}const k=e.query.rglst.reduce(((e,t)=>e+t.stop-t.start),0),q=e.query.translatecoding&&k<3*l;let x;if(q){if(!e.query.genome)throw"genome missing for translating genes";if(x=t[e.query.genome],!x)throw"invalid genome"}const N=[],A=(0,S.createCanvas)(10,10);let C=A.getContext("2d");e.query.devicePixelRatio>1&&C.scale(e.query.devicePixelRatio,e.query.devicePixelRatio);C.font="bold "+c+"px Arial";const j=v.length<Hn,T=v.length<Hn?[]:null;let M=!1;u&&(M=u.reverse);for(const t of e.query.rglst)t.reverse&&(M=!0);v.sort(((e,t)=>M?e.stop==t.stop?e.start-t.start:t.stop-e.stop:e.start==t.start?t.stop-e.stop:e.start-t.start));const O=v.some((e=>e.exon)),I=[0];let E=1,R=null;for(const t of v){let n=null,s=null;for(const r of t.rglst){let o=0;for(let t=0;t<r.idx;t++)o+=e.query.rglst[t].width+a;const i=e.query.rglst[r.idx],l=Math.max(t.start,i.start),c=Math.min(t.stop,i.stop);if(l<c){const e=o+i.scale(i.reverse?c:l),t=o+i.scale(i.reverse?l:c);null==n?(n=e,s=t):(n=Math.min(n,e),s=Math.max(s,t))}}if(null==n)continue;t.canvas={start:n,stop:s,stranded:null!=t.strand},t.coding&&q&&(t.willtranslate=!0,N.push(t));let r=n,o=s;if(j){const e=t.name;if(e){t.canvas.namestr=e;const n=C.measureText(e).width;t.canvas.namewidth=n,O?t.canvas.start>=n+Un?(t.canvas.namestart=t.canvas.start-Un,r=t.canvas.namestart-n,t.canvas.textalign="right"):t.canvas.stop+n+Un<=l?(t.canvas.namestart=t.canvas.stop+Un,o=t.canvas.namestart+n,t.canvas.textalign="left"):n>t.canvas.stop-t.canvas.start?t.canvas.start>l-t.canvas.stop?(t.canvas.namestart=t.canvas.start-Un,r=t.canvas.namestart-n,t.canvas.textalign="right"):(t.canvas.namestart=t.canvas.stop+Un,o=t.canvas.namestart+n,t.canvas.textalign="left"):(t.canvas.namehover=!0,t.canvas.textalign="left"):Math.min(l,t.canvas.stop)-Math.max(0,t.canvas.start)>=n+2*Jn?t.canvas.namein=!0:t.canvas.start>=n+Un?(t.canvas.namestart=t.canvas.start-Un,r=t.canvas.namestart-n,t.canvas.textalign="right"):t.canvas.stop+n+Un<=l?(t.canvas.namestart=t.canvas.stop+Un,o=t.canvas.namestart+n,t.canvas.textalign="left"):t.canvas.namein=!0}}t.canvas.stop-t.canvas.start>.3*l&&(R=[]);for(let e=1;e<=E;e++)if(null==I[e]||I[e]<r){t.canvas.stack=e,I[e]=o;break}null==t.canvas.stack&&(E++,I[E]=o,t.canvas.stack=E),es(T,r,o,t.canvas.stack,t)}A.width=l*e.query.devicePixelRatio;const D=(o+i)*E-i;A.height=D*e.query.devicePixelRatio,C=A.getContext("2d"),e.query.devicePixelRatio>1&&C.scale(e.query.devicePixelRatio,e.query.devicePixelRatio);C.font="bold "+c+"px Arial",C.textBaseline="middle",C.lineWidth=1;for(const t of v){const n=t.canvas;if(!n)continue;const s=m&&t.category&&m[t.category]?m[t.category].color:t.color||f,r=(o+i)*(n.stack-1);C.fillStyle=s,(t.exon||t.rglst.length>1)&&(C.strokeStyle=s,C.beginPath(),C.moveTo(n.start,Math.floor(r+o/2)+.5),C.lineTo(n.stop,Math.floor(r+o/2)+.5),C.stroke());for(const i of t.rglst){let l=0;for(let t=0;t<i.idx;t++)l+=e.query.rglst[t].width+a;const c=e.query.rglst[i.idx],f=[];t.utr3&&f.push(...t.utr3),t.utr5&&f.push(...t.utr5),!t.exon||t.coding&&0!=t.coding.length||f.push(...t.exon);for(const e of f){const n=Math.max(e[0],c.start),i=Math.min(e[1],c.stop);if(n<i){if(t.exon2color)for(const e of t.exon2color)if(n>=e.start&&i<=e.stop){C.fillStyle=e.color;break}const e=l+c.scale(c.reverse?i:n),a=l+c.scale(c.reverse?n:i);C.fillRect(e,r+w,Math.max(1,a-e),o-2*w),t.exon2color&&(C.fillStyle=s)}}const u=[];t.exon?t.coding&&t.coding.length>0&&u.push(...t.coding):u.push([t.start,t.stop]);let d=t.strand;n.stranded&&c.reverse&&(d="+"==t.strand?"-":"+");for(const e of u){const i=Math.max(e[0],c.start),a=Math.min(e[1],c.stop);if(i<a){if(t.exon2color)for(const e of t.exon2color)if(i>=e.start&&a<=e.stop){C.fillStyle=e.color;break}const e=l+c.scale(c.reverse?a:i),f=l+c.scale(c.reverse?i:a);if(C.fillRect(e,r,Math.max(1,f-e),o),t.exon2color&&(C.fillStyle=s),n.stranded&&!t.willtranslate)if(C.strokeStyle="white",n.namein){const t=(f-e-n.namewidth)/2;ts(C,d,e,r+w,t,o-2*w),ts(C,d,e+t+n.namewidth,r+w,t,o-2*w)}else ts(C,d,e,r+w,f-e,o-2*w)}}if(n.stranded&&t.intron){C.strokeStyle=s;for(const e of t.intron){const t=Math.max(e[0],c.start),n=Math.min(e[1],c.stop);if(t<n){const e=l+c.scale(c.reverse?n:t);ts(C,d,e,r+w,l+c.scale(c.reverse?t:n)-e,o-2*w)}}}if(R&&t.exon){for(let e=0;e<t.exon.length;e++){const s=t.exon[e];if(s[1]<=c.start||s[0]>=c.stop)continue;const r=Math.max(s[0],c.start),o=Math.min(s[1],c.stop);if(r<o){const i=l+c.scale(c.reverse?o:r),a=l+c.scale(c.reverse?r:o);R.push({chr:t.chr,start:Math.min(s[0],s[1]),stop:Math.max(s[0],s[1]),x1:i,x2:a,y:n.stack,name:"Exon "+(e+1)+"/"+t.exon.length})}}for(let e=1;e<t.exon.length;e++){const s=t.exon["+"==t.strand?e-1:e][1],r=t.exon["+"==t.strand?e:e-1][0];if(r<=c.start||s>=c.stop)continue;const o=Math.max(s,c.start),i=Math.min(r,c.stop);if(o<i){const a=l+c.scale(c.reverse?i:o),f=l+c.scale(c.reverse?o:i);if(f<0)continue;R.push({chr:t.chr,start:s,stop:r,x1:a,x2:f,y:n.stack,name:"Intron "+e+"/"+(t.exon.length-1)})}}}}if(null!=n.namestart)C.textAlign=n.textalign,C.fillStyle=s,C.fillText(n.namestr,n.namestart,r+o/2);else if(n.namehover&&!e.query.noNameHover){const e=Math.max(10,n.start+10);C.fillStyle="white",C.fillRect(e,r,n.namewidth+10,o),C.strokeStyle=s,C.strokeRect(e+1.5,r+.5,n.namewidth+10-3,o-2),C.fillStyle=s,C.textAlign="center",C.fillText(n.namestr,e+n.namewidth/2+5,r+o/2)}else n.namein&&(C.textAlign="center",C.fillStyle="white",C.fillText(n.namestr,(Math.max(0,n.start)+Math.min(l,n.stop))/2,r+o/2))}const L={height:D,mapisoform:T,mapexon:R,returngmdata:_};if(0==N.length)return L.src=A.toDataURL(),L;const P=[];C.textAlign="center",C.textBaseline="middle";for(const[t,n]of N.entries()){const t=m&&n.category&&m[n.category]?m[n.category].color:n.color||f,s=n.canvas,r=(o+i)*(s.stack-1);n.genomicseq=(await F.Kf(x,n.chr+":"+(n.start+1)+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase();const l=(0,$.nt2aa)(n);for(const t of n.rglst){const i=e.query.rglst[t.idx];let c=0;for(let n=0;n<t.idx;n++)c+=e.query.rglst[n].width+a;const f=i.width/(i.stop-i.start),u=Math.min(o,3*f),d=u<8?null:u;let p=!1;s.stranded&&"-"==n.strand&&(p=!0);let m=0;d&&(C.font=d+"px Arial");for(const[e,t]of n.coding.entries()){let[s,a]=t;if(p){if(s>=i.stop){m+=a-s,0==e&&n.startCodonFrame&&(m-=3-n.startCodonFrame);continue}if(a<=i.start)break}else{if(a<=i.start){m+=a-s,0==e&&n.startCodonFrame&&(m-=3-n.startCodonFrame);continue}if(s>=i.stop)break}if(0==e&&n.startCodonFrame){p?a-=3-n.startCodonFrame:s+=3-n.startCodonFrame;let e=Math.max(t[0],i.start),l=Math.min(t[1],i.stop);if(p?e=Math.max(a,i.start):l=Math.min(s,i.stop),e<l){C.fillStyle=Qn;const t=c+i.scale(i.reverse?l:e),n=c+i.scale(i.reverse?e:l);C.fillRect(t,r,Math.max(1,n-t),o)}}const u=Math.max(i.start,s),h=Math.min(i.stop,a);m+=p?a-h:u-s;let g=0;for(let e=0;e<h-u;e++){let t;if(m++,g++,m%3==0)t=m/3-1;else{if(e<h-u-1)continue;t=Math.floor(m/3)}let s=l[t],a=Math.ceil(m/3)%2==0?Zn:null;s?"M"==s?a=Xn:"*"==s&&(a=Yn):(s=4,a=Kn);let y,b=f*g;if(p){const t=h-1-e;y=c+i.scale(t)}else{const t=u+e+1-g;y=c+i.scale(t)}i.reverse&&(y-=b),g=0,y>=c&&y<=c+i.width&&(a&&(C.fillStyle=a,C.fillRect(y,r,b,o)),d&&(C.fillStyle="white",C.fillText(s,y+b/2,r+o/2)),P.push({x1:y,x2:y+b,y:n.canvas.stack,name:s+(t+1)+' <span style="font-size:.7em;color:#858585">AA residue</span>'}))}}}if(s.namehover&&!e.query.noNameHover){C.font="bold "+c+"px Arial";const e=Math.max(10,s.start+10);C.fillStyle="white",C.fillRect(e,r,s.namewidth+10,o),C.strokeStyle=t,C.strokeRect(e+1.5,r+.5,s.namewidth+10-3,o-2),C.fillStyle=t,C.fillText(s.namestr,e+s.namewidth/2+5,r+o/2)}}return L.src=A.toDataURL(),L.mapaa=P,L}(t,e))}catch(e){n.send({error:e.message||e}),e.stack&&console.log(e.stack)}}}(Pr)),Jr.post(Hr+"/tkbedgraphdot",function(e){return async(t,n)=>{try{const s=t.query,o=e[s.genome];if(!o)throw"unknown genome";let i=null;if(s.file)s.file=y().join(r().tpmasterdir,s.file);else{if(!s.url)throw"file or url missing";i=await F.d1(s.url,s.indexURL)}const a=await F.Jy(s.file||s.url,i,o),l=await Ce(s,i,a);n.send(l)}catch(e){e.stack&&console.log(e.stack),n.send({error:e.message||e})}}}(Pr)),Jr.all(Hr+"/tkbam",function(e){return async(t,n)=>{try{if(t.query.gdcFileUUID){if("string"!=typeof t.query.gdcFileUUID)throw"gdcFileUUID not string";!function(e){if(!e.query.gdcFilePosition)throw"gdcFileUUID is present but gdcFilePosition is missing";if("string"!=typeof e.query.gdcFilePosition)throw"gdcFilePosition is not string";if("unmapped"==e.query.gdcFilePosition)return;const t=e.query.gdcFilePosition.split(/[.:-]/);if(3!=t.length)throw"gdcFilePosition not 3 fields";const n=Number(t[1]),s=Number(t[2]);if(!Number.isInteger(n)||!Number.isInteger(s)||n>s)throw"gdcFilePosition invalid start/stop";if(e.query.stream2download)return;if(s-n>en)throw`Slice range exceeds ${Ge(en)} limit. Please choose a smaller range.`}(t),t.query.__genomes=e;const s=t.get("X-Auth-Token");if(s&&(t.query.token=s),await Qe(t.query.gdcFileUUID,tn(e),t.query),t.query.stream2download)return void await async function(e,t){const{host:n,headers:s}=tn(e.query.__genomes).getHostHeaders(e.query);s.compression=!1;const r=y().join(n.rest,"/slicing/view/",e.query.gdcFileUUID+"?region="+e.query.gdcFilePosition);t.statusCode=200;try{await tt(v().stream(r,{method:"get",headers:s}),t)}catch(e){if("ERR_STREAM_PREMATURE_CLOSE"==e.code)return;e.stack&&console.log(e.stack),t.send({error:e.message||e})}}(t,n);t.query.file=Nn(t)}if(t.query.downloadgdc)return void n.send(await Sn(t));if(t.query.clientdownloadgdcslice)return void await async function(e,t){if(!e.query.gdcFileUUID||!e.query.gdcFilePosition||!e.query.file)throw"clientdownloadgdcslice: unauthorized access";const n=y().join(r().cachedir_bam,e.query.file),s=await h().promises.readFile(n);t.writeHead(200,{"Content-Type":"application/octet-stream","Content-Disposition":"attachment; filename=gdc.bam","Content-Length":s.length}),t.end(Buffer.from(s,"binary"))}(t,n);if(!t.query.genome)throw".genome missing";const s=e[t.query.genome];if(!s)throw"invalid genome";if(t.query.getread)return void n.send(await async function(e,t){if(!t.query.chr)throw".chr missing";if(!t.query.qname)throw".qname missing";if(t.query.qname=decodeURIComponent(t.query.qname),!Number.isInteger(t.query.start))throw".start is not integer";if(!Number.isInteger(t.query.stop))throw".stop is not integer";const n={chr:t.query.chr,start:t.query.start,stop:t.query.stop,scale:()=>{},ntwidth:10},s=await async function(e,t){const[n,s]=await rn(e);let r,o,i,a,l;if(e.query.unknownorder){if(!Number.isInteger(e.query.readstart)||!Number.isInteger(e.query.readstop))throw"readstart/stop not provided for read with unknown order";i=e.query.readstart,a=e.query.readstop}if(await F.UE({isbam:!0,args:["view",n,(e.query.nochr?e.query.chr.replace("chr",""):e.query.chr)+":"+t.start+"-"+t.stop],dir:s,callback:(n,s)=>{if(n.split("\t")[0]!=e.query.qname)return;const c=dn({sam_info:n,keepallboxes:!0,keepmatepos:!0,keepunmappedread:!0},t);if(c&&(!e.query.show_unmapped||!c.discord_unmapped2)&&(e.query.start==c.segstart_original&&e.query.stop==c.segstop||e.query.paired||e.query.show_unmapped))if(e.query.show_unmapped&&e.query.getfirst){if(c.islast)return s.kill(),void(l=[c])}else if(e.query.show_unmapped&&e.query.getlast){if(c.isfirst)return s.kill(),void(l=[c])}else if(e.query.getfirst){if(c.isfirst)return s.kill(),void(l=[c])}else if(e.query.getlast){if(c.islast)return s.kill(),void(l=[c])}else if(e.query.unknownorder){if(c.segstart==i&&c.segstop==a)return s.kill(),void(l=[c])}else if(c.isfirst?r=c:c.islast&&(o=c),r&&o)return s.kill(),void(l=[r,o])}}),l){if(e.query.altseqs){const t={query_seq:l[0].seq,refseqs:e.query.refseqs,altseqs:e.query.altseqs,cigar_seq:l[0].cigarstr,start_position:l[0].segstart,ref_positions:e.query.ref_positions,refalleles:e.query.refalleles,altalleles:e.query.altalleles},n=(await(0,_e.run_rust)("align",JSON.stringify(t))).split("\n");let s;for(let e of n)e.includes("Final_output:")?s=JSON.parse(e.replace("Final_output:","")):console.log(e);l.alignments=s}return l}l=[],r&&l.push(r);o&&l.push(o);return l.length?l:null}(t,n);if(!s){if(t.query.show_unmapped)throw"mate not found";throw"read not found"}const r=[];for(const n of s)n.discord_unmapped1?r.push(await qn(n,e,t.query)):r.push(await xn(n,e,t.query));s.alignments&&(r[0].alignments=s.alignments);return{lst:r}}(s,t));const o=r().debugmode?new Date:null,i=await async function(e,t){const[n,s]=await rn(t),r={genome:e,file:n,dir:s,asPaired:t.query.asPaired,getcolorscale:t.query.getcolorscale,devicePixelRatio:t.query.devicePixelRatio?Number(t.query.devicePixelRatio):1};if(t.query.pileupheight&&(r.pileupheight=Number(t.query.pileupheight),Number.isNaN(r.pileupheight)))throw".pileupheight is not integer";t.query.drop_pcrduplicates&&(r.drop_pcrduplicates=!0);t.query.drop_supplementary_alignments&&(r.drop_supplementary_alignments=!0);if(t.query.variant){r.diff_score_plotwidth=Number(t.query.diff_score_plotwidth),t.query.max_diff_score&&(r.max_diff_score=Number(t.query.max_diff_score),r.min_diff_score=Number(t.query.min_diff_score));const e=t.query.variant.split(".");if(r.strictness=t.query.strictness,!Number.isInteger(e.length%4))throw"invalid variant, not chr.pos.ref.alt";r.alleleAlreadyUpdated=t.query.alleleAlreadyUpdated,r.alleleAlreadyUpdated&&(r.altseqs=t.query.altseqs,r.refseqs=t.query.refseqs,r.altalleles=t.query.altalleles,r.refalleles=t.query.refalleles,r.leftflankseqs=t.query.leftflankseqs,r.rightflankseqs=t.query.rightflankseqs,r.ref_positions=t.query.ref_positions);const n=e.length/4,s=[];for(let t=0;t<n;t++)s.push({chr:e[4*t],pos:Number(e[4*t+1]),ref:e[4*t+2],alt:e[4*t+3]});if(r.variant=s,t.query.alignOneGroup&&(r.alignOneGroup=t.query.alignOneGroup),Number.isNaN(r.variant.pos))throw"variant pos not integer"}else if(t.query.sv){const e=t.query.sv.split(".");if(e.length<6)throw"invalid sv, not chrA.posA.chrB.posB";if(r.sv={chrA:e[0],startA:Number(e[1]),strandA:Number(e[2]),chrB:e[3],startB:Number(e[4]),strandB:Number(e[5])},Number.isNaN(r.sv.startA))throw"sv.startA not integer";if(Number.isNaN(r.sv.startB))throw"sv.startB not integer"}if(Number.isFinite(Number(t.query.stackstart))){if(!t.query.stackstop)throw".stackstop missing";if(r.partstack={start:Number(t.query.stackstart),stop:Number(t.query.stackstop)},Number.isNaN(r.partstack.start))throw".stackstart not integer";if(Number.isNaN(r.partstack.stop))throw".stackstop not integer";if(!t.query.grouptype)throw".grouptype required for partstack";r.grouptype=t.query.grouptype}t.query.gdc||(t.query.nochr?r.nochr="string"==typeof t.query.nochr?JSON.parse(t.query.nochr):t.query.nochr:r.nochr=await F.Dp(r.file,e,r.dir));if(r.regions=t.query.regions,!Array.isArray(r.regions)||0==r.regions.length)throw"q.regions[] not non-empty array";let o=0;for(const e of r.regions){if(!e.chr)throw".chr missing from a region";if(!Number.isInteger(e.start))throw".start not integer of a region";if(!Number.isInteger(e.stop))throw".stop not integer of a region";e.scale=t=>Math.ceil(e.width*(t-e.start)/(e.stop-e.start)),e.ntwidth=e.width/(e.stop-e.start),o=Math.max(o,e.ntwidth)}return r.stacksegspacing=Math.max(Jt,Ht*o),r.readcount_skipped=0,r}(s,t);n.send(await async function(e){await async function(e){if(e.variant){let t=0,n=0,s=0,r=e.variant[0].pos,o=e.variant[0].pos+Math.max(e.variant[0].ref.length,e.variant[0].alt.length);for(const i of e.variant){const e=Math.abs(i.pos-Math.max(i.ref.length,i.alt.length));e>t&&(t=e,n=s),r>i.pos&&(r=i.pos),o<i.pos+Math.max(i.ref.length,i.alt.length)&&(o=i.pos+Math.max(i.ref.length,i.alt.length)),s+=1}t=Math.floor(1.5*Math.max(e.variant[n].ref.length,e.variant[n].alt.length));const i={chr:e.variant[0].chr,start:r-t,stop:o+t};return await an(e,[i]),await ln(i,e),void(e.regions[0].lines=i.lines)}await an(e,e.regions);for(const t of e.regions)await ln(t,e)}(e),e.totalnumreads=e.regions.reduce(((e,t)=>e+t.lines.length),0);const t={nochr:e.nochr,count:{r:e.totalnumreads},groups:[]};e.read_limit_reached&&(t.count.read_limit_reached=e.read_limit_reached);e.canvaswidth=e.regions[e.regions.length-1].x+e.regions[e.regions.length-1].width;{const n=await async function(e){const t=[],n=[];let s=0;for(const r of e.regions){for(const e of r.lines)t.push({sam_info:e,tempscore:""});s=r.x+r.width,n.push(s)}if(0==t.length)return{groups:[{type:Te,regions:$e(e.regions),templates:t,messages:[],partstack:e.partstack,widths:n}]};if(e.variant){if(1==e.regions.length)return await async function(e,t,n){const s=e.regions[0].lines[0].split("\t")[9].length;let r=!1,o=[],i=[],a=[],l=[],c=[],f=[],u=[];if(e.alleleAlreadyUpdated)o=e.leftflankseqs,i=e.rightflankseqs,f=e.refseqs,u=e.altseqs,a=e.refalleles,l=e.altalleles,c=e.ref_positions,0!=f[0].toUpperCase().localeCompare((o[0]+a[0]+i[0]).toUpperCase())&&(console.log("Reference allele is not correct for variant 0"),r=!0);else{let t,n,r=0;for(const o of e.variant){let i="",f="";if(!(0!=o.ref.length&&"-"!=o.ref||"-"!=o.alt&&0!=o.alt.length))throw"Both Ref and Alt alleles are missing";if(0==o.ref.length||"-"==o.ref)i=(await F.Kf(e.genome,o.chr+":"+o.pos+"-"+o.pos)).split("\n").slice(1).join("").toUpperCase(),f=i+o.alt,o.pos-=1;else if("-"==o.alt||0==o.alt.length){const t=(await F.Kf(e.genome,o.chr+":"+o.pos+"-"+o.pos)).split("\n").slice(1).join("").toUpperCase();i=t+o.ref,f=t,o.pos-=1}else f=o.alt,i=o.ref;const u=o.pos,d=i.toUpperCase(),p=f.toUpperCase();0==r?(t=u-s,n=u+i.length+1+s):(u-s<t&&(t=u-s),u+i.length+1+s>n&&(n=u+i.length+1+s)),a.push(d),l.push(p),c.push(u),r+=1}r=0;for(const s of e.variant){const d=(await F.Kf(e.genome,s.chr+":"+t+"-"+c[r])).split("\n").slice(1).join("").toUpperCase(),p=(await F.Kf(e.genome,s.chr+":"+(c[r]+a[r].length+1)+"-"+n)).split("\n").slice(1).join("").toUpperCase(),m=d+a[r]+p,h=d+l[r]+p;console.log(s.chr+"."+c[r]+"."+a[r]+"."+l[r]),r+=1,o.push(d),i.push(p),f.push(m),u.push(h)}}const d=[];for(let e=0;e<t.length;e++){const n=t[e].sam_info.split("\t");d.push({read_sequence:n[9],start_position:Number(n[3]),cigar:n[5],flag:Number(n[1])})}const p=[];for(let e=0;e<a.length;e++)p.push({ref_position:Number(c[e]),refallele:a[e],altallele:l[e],refseq:f[e],altseq:u[e],leftflankseq:o[e],rightflankseq:i[e]});Number.isFinite(Number(e.strictness))||(e.strictness=1);const m={reads:d,alleles:p,strictness:Number(e.strictness)},h=new Date,g=await(0,_e.run_rust)("indel",JSON.stringify(m)),y=new Date;console.log("Time taken to run rust indel pipeline:",y-h,"ms");const b=g.split("\n");let v,w,_,k,q,x,N=0;for(let e of b)e.includes("Final_output:")?v=JSON.parse(JSON.parse(e.replace("Final_output:",""))):1==a.length&&e.includes("fisher_strand:")?(w=JSON.parse(e.replace("fisher_strand:","")),_=w.alternate_forward_count,k=w.alternate_reverse_count,q=w.reference_forward_count,x=w.reference_reverse_count,N=w.p_value):console.log(e);if(0==v.length)throw"No reads available for variant typing";let S=!1;1==e.variant.length&&N>60&&(S=!0);const A=Fe(e);e.variant.length;let C=1;for(let n=0;n<v.length;n++){const s=v[n],r=s.read_number,o=s.categories,i=s.categories[0],a=[];if(o.length>1){for(let e=1;e<o.length;e++)a.push(o[e]);o.length-1>C&&(C=o.length-1)}if(i.includes("alt"))for(let n=0;n<e.variant.length;n++)i=="alt"+n.toString()&&A[Oe+n.toString()]&&(t[r].tempscore=["alt"+n.toString()],A[Oe+n.toString()].templates.push(t[r]));else"ref"==i?A[Me]&&(t[r].tempscore=["ref"],A[Me].templates.push(t[r])):"none"==i?A[Ie]&&(t[r].tempscore=a,A[Ie].templates.push(t[r])):"amb"==i?A[Ee]&&(t[r].tempscore=a,A[Ee].templates.push(t[r])):console.log("Unaccounted group, please check")}const j=[];for(const t in A){const s=A[t];if(0!=s.templates.length){if(t.includes(Oe))for(let n=0;n<e.variant.length;n++)t==Oe+n.toString()&&(1==e.variant.length?1==s.templates.length?s.messages.push({isheader:!0,t:s.templates.length+" read supporting the alternative allele"}):s.messages.push({isheader:!0,t:s.templates.length+" reads supporting the alternative allele"}):1==s.templates.length?s.messages.push({isheader:!0,t:s.templates.length+" read support the alternative allele with "+l[n]+" sequence"}):s.messages.push({isheader:!0,t:s.templates.length+" reads support the alternative allele with "+l[n]+" sequence"}));else t==Ee?1==s.templates.length?s.messages.push({isheader:!0,t:s.templates.length+" ambiguous read"}):s.messages.push({isheader:!0,t:s.templates.length+" ambiguous reads"}):t==Me?1==s.templates.length?s.messages.push({isheader:!0,t:s.templates.length+" read supporting the reference allele"}):s.messages.push({isheader:!0,t:s.templates.length+" reads supporting the reference allele"}):t==Ie?1==s.templates.length?s.messages.push({isheader:!0,t:s.templates.length+" read supporting neither reference nor alternative alleles"}):s.messages.push({isheader:!0,t:s.templates.length+" reads supporting neither reference nor alternative alleles"}):console.log("Unaccounted group, please check");s.widths=n,j.push(s)}}const T=[];for(let e=0;e<j.length;e++)j[e].type.includes("support_alt")&&T.push(j[e]);for(let e=0;e<j.length;e++)"support_ref"==j[e].type&&T.push(j[e]);for(let e=0;e<j.length;e++)"support_no"==j[e].type&&T.push(j[e]);for(let e=0;e<j.length;e++)"support_amb"==j[e].type&&T.push(j[e]);return{groups:T,refalleleerror:r,ref_positions:c,refalleles:a,altalleles:l,max_diff_score:C,min_diff_score:0,strand_probability:N,strand_significance:S,refseqs:f,altseqs:u,leftflankseqs:o,rightflankseqs:i,alternate_forward_count:_,alternate_reverse_count:k,reference_forward_count:q,reference_reverse_count:x}}(e,t,n);console.log("Indel pipeline works only in single region. Please check!")}if(e.sv&&e.regions.length>1)return async function(e,t,n){const s=Fe(t),r=[];for(let e=0;e<t.regions.length;e++){const n=t.regions[e],s=(await F.Kf(t.genome,n.chr+":"+n.start+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase(),o=[];for(const t of n.lines)o.push({sam_info:t,tempscore:"",ridx:e});const i={refseq:s,start:n.start,stop:n.stop,entries:o};0==e?(i.chr=t.sv.chrA,i.pos=t.sv.startA):1==e?(i.chr=t.sv.chrB,i.pos=t.sv.startB):console.log("More than two regions, please check"),r.push(i)}const o=new Date,i=(await(0,_e.run_rust)("sv",JSON.stringify(r))).split("\n"),a=new Date;let l,c;console.log("Time taken to run rust SV pipeline:",a-o,"ms");for(let e of i)e.includes("multi_region_templates:")?l=JSON.parse(e.replace("multi_region_templates:","")):e.includes("single_region_templates:")&&(c=JSON.parse(e.replace("single_region_templates:","")));if(!t.grouptype||"support_sv"==t.grouptype)for(const e of l)s[Re].templates.push(e);if(!t.grouptype||"support_ref"==t.grouptype)for(const e of c)s[Me].templates.push(e);const f=[];for(const e in s){const t=s[e];0!=t.templates.length&&(e==Re?1==t.templates.length?t.messages.push({isheader:!0,t:t.templates.length+" read supporting SV/fusion"}):t.messages.push({isheader:!0,t:t.templates.length+" reads supporting SV/fusion"}):e==Me&&t.messages.push({isheader:!0,t:t.templates.length+" reads supporting reference allele"}),t.widths=n,f.push(t))}return{groups:f}}(0,e,n);return{groups:[{type:Te,regions:$e(e.regions),templates:t,messages:[],partstack:e.partstack,widths:n}]}}(e);e.groups=n.groups,e.variant&&(t.ref_alleles=n.refalleles,t.alt_alleles=n.altalleles,t.allele_positions=n.ref_positions,t.strand_probability=n.strand_probability,t.alternate_forward_count=n.alternate_forward_count,t.reference_forward_count=n.reference_forward_count,t.alternate_reverse_count=n.alternate_reverse_count,t.reference_reverse_count=n.reference_reverse_count,1==n.strand_significance&&(t.strand_significance=!0),e.alleleAlreadyUpdated||(t.refseqs=n.refseqs,t.altseqs=n.altseqs,t.leftflankseqs=n.leftflankseqs,t.rightflankseqs=n.rightflankseqs,t.ref_positions=n.ref_positions,t.refalleles=n.refalleles,t.altalleles=n.altalleles)),Number.isFinite(e.max_diff_score)&&e.variant?(t.max_diff_score=e.max_diff_score,t.min_diff_score=e.min_diff_score):Number.isFinite(n.max_diff_score)&&(t.max_diff_score=n.max_diff_score,t.min_diff_score=n.min_diff_score),n.refalleleerror&&(t.refalleleerror=n.refalleleerror)}if(0==t.count.r)throw"No reads in view range.";if(e.alignOneGroup){const t=e.groups.find((t=>t.type==e.alignOneGroup));if(!t)throw"cannot find group for realignment";let n=un(e,t);return n=mn(t,e,n),await async function(e,t,n){let s;if(t.variant)if("support_ref"==e.type){let r=t.leftflankseqs[0].length;s=e.partstack?await on(n,r,e.partstack.start,e.partstack.stop,t.refseqs[0]):await on(n,r,0,0,t.refseqs[0])}else if("support_no"==e.type){let r=t.leftflankseqs[0].length;s=e.partstack?await on(n,r,e.partstack.start,e.partstack.stop):await on(n,r)}else{if("support_amb"==e.type)throw"Realignment of reads in ambiguous group is not currently implemented.";if(e.type.includes("support_alt")){for(let r=0;r<t.variant.length;r++)if(e.type=="support_alt"+r.toString()){let o=t.leftflankseqs[r].length;s=e.partstack?await on(n,o,e.partstack.start,e.partstack.stop,t.altseqs[r]):await on(n,o,0,0,t.altseqs[r])}}else console.log("Unaccounted group, please check")}return{alignmentData:s}}(t,e,n)}let n=[];for(const s of e.groups){let r=un(e,s);r=mn(s,e,r),await pn(s,e,r),await fn(r,e),gn(s,r,e);const o={type:s.type,width:e.canvaswidth,height:s.canvasheight,stackheight:s.stackheight,stackcount:s.stacks.length,allowpartstack:s.allowpartstack,templatebox:s.returntemplatebox,count:{r:r.reduce(((e,t)=>e+t.segments.length),0)}},i=(0,S.createCanvas)(e.canvaswidth*e.devicePixelRatio,s.canvasheight*e.devicePixelRatio),a=i.getContext("2d");e.devicePixelRatio>1&&a.scale(e.devicePixelRatio,e.devicePixelRatio),a.textAlign="center",a.textBaseline="middle",o.messages=s.messages,o.messagerowheights=0;for(const t of r)wn(a,t,s,e);kn(a,s,e,r),e.asPaired&&(o.count.t=r.length),e.variant&&(o.diff_scores_img=await 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F.d1(f,e.query.indexURL))),e.query.autoscale)a=!0;else if(e.query.percentile){if(o=e.query.percentile,!Number.isFinite(o))throw"invalid percentile"}else{if(n=e.query.minv,s=e.query.maxv,!Number.isFinite(n))throw"invalid minv";if(!Number.isFinite(s))throw"invalid maxv"}if(!Number.isFinite(e.query.barheight))throw"invalid barheight";if(!Number.isFinite(e.query.regionspace))throw"invalid regionspace";if(!Number.isFinite(e.query.width))throw"invalid width";if(!e.query.rglst)throw"region list missing";if(e.query.dotplotfactor&&!Number.isInteger(e.query.dotplotfactor))throw"dotplotfactor value should be positive integer";if(l)return await async function(e,t,n,s,r,o){if(null==n||null==s)throw"Y axis scale must be defined for bedgraph track";const i=(0,S.createCanvas)(e.query.width*e.query.devicePixelRatio,e.query.barheight*e.query.devicePixelRatio),a=i.getContext("2d");e.query.devicePixelRatio>1&&a.scale(e.query.devicePixelRatio,e.query.devicePixelRatio);let l=0;for(let t of e.query.rglst)await qe(e,t,l,n,s,r,o,a),l+=t.width+e.query.regionspace;t.send({src:i.toDataURL()})}(e,t,n,s,f,i);for(const t of e.query.rglst){let n;if(r().features.bigwig_rust){const s=f+","+t.chr+","+t.start+","+t.stop+","+Math.ceil(t.width*(e.query.dotplotfactor||1));n=await(0,_e.run_rust)("bigwig",s)}else n=await Ne(e,t,f);n&&(t.values=n.trim().split("\t").map(Number.parseFloat),e.query.dividefactor&&(t.values=t.values.map((t=>t/e.query.dividefactor))))}let d=!0;for(const t of e.query.rglst)t.values&&(d=!1);const p=(0,S.createCanvas)(e.query.width*e.query.devicePixelRatio,e.query.barheight*e.query.devicePixelRatio),m=p.getContext("2d");if(e.query.devicePixelRatio>1&&m.scale(e.query.devicePixelRatio,e.query.devicePixelRatio),d)return m.font="14px Arial",m.fillStyle="#858585",m.textAlign="center",m.textBaseline="middle",m.fillText(e.query.name+": no data in view range",e.query.width/2,e.query.barheight/2),void t.send({src:p.toDataURL(),nodata:!0});const h=1,g=e.query.dotplotfactor?1/e.query.dotplotfactor:1;let y=0,b=0;const v={};if(a||o){const t=[],n=[];for(const s of e.query.rglst)if(s.values)for(const e of s.values)Number.isNaN(e)||(e>=0&&t.push(e),e<=0&&n.push(e));t.length&&(t.sort(((e,t)=>e-t)),y=a?t[t.length-1]:t[Math.floor(t.length*o/100)]),n.length&&(n.sort(((e,t)=>t-e)),b=a?n[n.length-1]:n[Math.floor(n.length*o/100)]),v.minv=b,v.maxv=y}else b=n,y=s;if(e.query.barheight<10){let t=(0,ke.B8)(e.query.pcolor);const n=t.r+","+t.g+","+t.b;t=(0,ke.B8)(e.query.ncolor);const s=t.r+","+t.g+","+t.b;let r=0;for(const t of e.query.rglst){if(t.values)for(let o=0;o<t.values.length;o++){const i=t.values[o];if(Number.isNaN(i))continue;m.fillStyle=i>=y?e.query.pcolor2:i>=0?"rgba("+n+","+i/y+")":i<=b?e.query.ncolor2:"rgba("+s+","+i/b+")";const a=Math.ceil(r+(t.reverse?t.width-g*o:g*o));m.fillRect(a,0,h,e.query.barheight)}r+=t.width+e.query.regionspace}}else{const t=xe().height(e.query.barheight).min(b).max(y);let n=0;for(const s of e.query.rglst){if(s.values)for(let r=0;r<s.values.length;r++){const o=s.values[r];if(Number.isNaN(o))continue;m.fillStyle=o>0?e.query.pcolor:e.query.ncolor;const i=Math.ceil(n+(s.reverse?s.width-g*r:g*r)),a=t(o);if(o>0)m.fillRect(i,a.y,h,e.query.dotplotfactor?Math.min(2,a.h):a.h);else if(e.query.dotplotfactor){const e=Math.min(2,a.h);m.fillRect(i,a.y+a.h-e,h,e)}else m.fillRect(i,a.y,h,a.h);o>y?(m.fillStyle=e.query.pcolor2,m.fillRect(i,0,h,2)):o<b&&(m.fillStyle=e.query.ncolor2,m.fillRect(i,e.query.barheight-2,h,2))}n+=s.width+e.query.regionspace}}v.src=p.toDataURL(),t.send(v)}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/tkld",function(e){return async(t,n)=>{try{const s=e[t.query.genome];if(!s)throw"unknown genome";n.send(await async function(e,t){const[n,s,r]=F.ZX(e);if(n)throw n;let o;r&&(o=await F.d1(s,e.query.indexURL));if(!e.query.rglst)throw"rglst missing";const i=await F.Jy(s,o,t),a=e.query.connheight||50,l={rglst:[]};for(const t of e.query.rglst){const n={chr:t.chr,start:t.start,stop:t.stop,width:t.width,reverse:t.reverse,xoff:t.xoff};l.rglst.push(n);const r=[],c=new Set,f=(i?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop;await F.UE({args:[s,f],dir:o,callback:e=>{const n=e.split("\t"),s=Number.parseInt(n[1]);if(s<t.start)return;const o=Number.parseInt(n[2]);if(o>t.stop)return;const i=Number.parseFloat(n[5]);r.push({start:s,stop:o,r2:i}),c.add(s),c.add(o)}}),n.img=Se(t,r,c,a,e.query.devicePixelRatio||1)}return l}(t,s))}catch(e){n.send({error:e.message||e})}}}(Pr)),Jr.get(Hr+"/tabixheader",(async function(e,t){try{const[n,s,r]=F.ZX(e);if(n)throw n;const o=r?await F.d1(s,e.query.indexURL):null,i=await F.ZD(s,o);t.send({lines:i})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.all(Hr+"/snp",(async function(e,t){try{const n=e.query.genome;if(!n)throw"no genome";t.send({results:await Qr(e.query,Pr[n])})}catch(e){return e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/isoformlst",(function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"invalid genome";if(!Array.isArray(e.query.lst))throw".lst missing";const s=[];for(const t of e.query.lst){if(n.genomicNameRegexp.test(t))continue;const e=n.genedb.getjsonbyisoform.all(t);s.push(e.map((e=>{const t=JSON.parse(e.genemodel);return e.isdefault&&(t.isdefault=!0),t})))}t.send({lst:s})}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Jr.post(Hr+"/dbdata",(function(e,t){})),Jr.get(Hr+"/img",(async function(e,t){const[n,s,r]=F.ZX(e);try{if(n)throw"invalid image file";const e=await h().promises.readFile(s);t.send({src:"data:image/jpeg;base64,"+new Buffer.from(e).toString("base64"),size:M()(s)})}catch(n){t.send({error:n.message||n})}})),Jr.post(Hr+"/svmr",(function(e,t){if(e.query.file){const[n,s,r]=F.ZX(e);if(n)return void t.send({error:"illegal file name"});h().readFile(s,"utf8",((e,n)=>{e?t.send({error:"cannot read file"}):t.send({raw:n})}))}else t.send({error:"missing file"})})),Jr.post(Hr+"/study",(async function(e,t){try{if(F.lY(e.query.file))throw"invalid file path";const n=y().join(r().tpmasterdir,e.query.file.endsWith(".json")?e.query.file:e.query.file+".json"),s=JSON.parse(await F.b5(n));if(!s.genome)throw"genome missing";const o={};let i=0;for(const e of s.mutationset||[]){const t=L.Dz(s.genome);if(!t)throw"init_bulk_flag() failed";if(s.mutationset.length>1&&(t.tpsetname=e.name?e.name:"set"+ ++i),o[Math.random()]=t,e.snvindel){const n=(await F.b5(y().join(r().tpmasterdir,e.snvindel))).trim().split(/\r?\n/),s=P.parseheader(n[0],t);if(s)throw"snvindel header line error: "+s;for(let e=1;e<n.length;e++)P.parseline(e,n[e],t)}if(e.sv){const n=(await F.b5(y().join(r().tpmasterdir,e.sv))).trim().split(/\r?\n/),s=U.parseheader(n[0],t,!0);if(s)throw"sv header line error: "+s;for(let e=1;e<n.length;e++)U.parseline(e,n[e],t,!0)}if(e.fusion){const n=(await F.b5(y().join(r().tpmasterdir,e.fusion))).trim().split(/\r?\n/),s=U.parseheader(n[0],t,!1);if(s)throw"fusion header line error: "+s;for(let e=1;e<n.length;e++)U.parseline(e,n[e],t,!1)}if(e.svjson){const n=(await F.b5(y().join(r().tpmasterdir,e.svjson))).trim().split(/\r?\n/),[s,o]=J.parseheader(n[0],t);if(s)throw"svjson header line error: "+s;for(let e=1;e<n.length;e++)J.parseline(e,n[e],t,o)}if(e.cnv){const n=(await F.b5(y().join(r().tpmasterdir,e.cnv))).trim().split(/\r?\n/),s=G.parseheader(n[0],t);if(s)throw"cnv header line error: "+s;for(let e=1;e<n.length;e++)G.parseline(e,n[e],t)}if(e.itd){const n=(await F.b5(y().join(r().tpmasterdir,e.itd))).trim().split(/\r?\n/),s=B.parseheader(n[0],t);if(s)throw"itd header line error: "+s;for(let e=1;e<n.length;e++)B.parseline(e,n[e],t)}if(e.deletion){const n=(await F.b5(y().join(r().tpmasterdir,e.deletion))).trim().split(/\r?\n/),s=z.parseheader(n[0],t);if(s)throw"deletion header line error: "+s;for(let e=1;e<n.length;e++)z.parseline(e,n[e],t)}if(e.truncation){const n=(await F.b5(y().join(r().tpmasterdir,e.truncation))).trim().split(/\r?\n/),s=H.parseheader(n[0],t);if(s)throw"Truncation header line error: "+s;for(let e=1;e<n.length;e++)H.parseline(e,n[e],t)}}if(s.annotations){const e=s.annotations.idkey?s.annotations.idkey:"sample";s.annotations.data={};for(const t of s.annotations.files){const n=await F.b5(y().join(r().tpmasterdir,t));ee(n).forEach((t=>{const n=t[e].trim();s.annotations.data[n]||(s.annotations.data[n]=[]),s.annotations.data[n].push(t)}))}}for(const e in o)te(o[e]);delete s.mutationset,t.send({cohort:s,flagset:o})}catch(e){return void t.send({error:e.message||e})}})),Jr.post(Hr+"/textfile",(function(e,t){if(!e.query.file)return t.send({error:"no file"});if(F.lY(e.query.file))return t.send({error:"invalid file name"});const n=y().join(r().tpmasterdir,e.query.file);if(null!=e.query.from){if(!Number.isInteger(e.query.from))return void t.send({error:"invalid value for from"});if(!Number.isInteger(e.query.to))return void t.send({error:"invalid value for to"});const s=[];_()(h().createReadStream(n)).on("end",(()=>{t.send({text:s.join("\n")})})).lines.map(String).skip(e.query.from-1).take(e.query.to).forEach((e=>{s.push(e)}))}else h().readFile(n,{encoding:"utf8"},((e,n)=>{e?t.send({error:"error reading file"}):t.send({text:n})}))})),Jr.post(Hr+"/urltextfile",(async function(e,t){const n=e.query.url.replace(r().URL,`http://127.0.0.1:${r().port}`);try{const e=await v()(n);switch(e.statusCode){case 200:return void t.send({text:F.cl(e.body)});case 404:return void t.send({error:"File not found: "+n});default:t.send({error:"unknown status code: "+e.status})}}catch(e){return t.send({error:"Error downloading file: "+n})}})),Jr.get(Hr+"/junction",(async function(e,t){try{const[n,s,o]=F.ZX(e);if(n)throw n;if(!e.query.rglst)throw"rglst[] missing";if("string"==typeof e.query.rglst&&(e.query.rglst=JSON.parse(e.query.rglst)),!Array.isArray(e.query.rglst))throw"rglst[] not an array";if(e.query.rglst.reduce(((e,t)=>t.stop-t.start+e),0)>1e6)throw"Zoom in below 1 Mb to show junctions";let i;if(e.query.isrnapeg){if(!r().features.junctionrnapeg)throw"rnapeg not supported on this server";if(o)throw"rnapeg file from url is not supported";i=await async function(e,t){try{await h().promises.stat(t)}catch(e){if("EACCES"==e.code)throw"permission denied for rnapeg file";if("ENOENT"==e.code)throw"rnapeg file not found";throw"cannot access rnapeg file ("+e.code+")"}const n=[];for(const s of e.rglst){const e=await Gn({file:t,chr:s.chr,start:s.start,stop:s.stop});for(const t of e)n.push(t)}return n}(e.query,s)}else{const t=o?await F.d1(s,e.query.indexURL):null;i=await async function(e,t,n){const s=[];for(const r of e.rglst)await F.UE({args:[t,r.chr+":"+r.start+"-"+r.stop],dir:n,callback:e=>{const t=e.split("\t"),n=Number.parseInt(t[1]),o=Number.parseInt(t[2]);if(n>=r.start&&n<=r.stop||o>=r.start&&o<=r.stop){const e={chr:r.chr,start:n,stop:o,type:t[4],rawdata:[]};for(let n=5;n<t.length;n++)e.rawdata.push(Number.parseInt(t[n]));s.push(e)}}});return s}(e.query,s,t)}t.send({lst:i})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/mdsjunction",function(e){return async(t,n)=>{try{const[s,o,i]=await async function(e,t){const n=e.query;if(!n.genome)throw"genome missing";const s=t[n.genome];if(!s)throw"invalid genome";let o={},i={};if(n.iscustom)if(i.listsamples=!0,n.url)i.url=n.url,i.dir=await F.d1(n.url,n.indexURL);else if(n.file)i.file=y().join(r().tpmasterdir,n.file);else{if(!n.file2)throw"no file or url given";i.file2=y().join(r().tpmasterdir,n.file2)}else{if(!s.datasets)throw"genome is not equipped with datasets";if(!n.dslabel)throw"dslabel missing";if(o=s.datasets[n.dslabel],!o)throw"invalid dslabel";if(!o.queries)throw"dataset is not equipped with queries";if(!n.querykey)throw"querykey missing";if(i=o.queries[n.querykey],!i)throw"invalid querykey"}return[n,o,i]}(t,e),a=await async function(e,t,n){if(e.junction)return await async function(e,t,n){const s=e.junction;if(!s.chr||!Number.isInteger(s.start)||!Number.isInteger(s.stop))throw"incomplete/invalid info about querying junction";let r;if(await F.UE({args:[$n(n),s.chr+":"+s.start+"-"+s.stop],dir:n.dir,callback:o=>{const i=o.split("\t"),a=Number.parseInt(i[1]),l=Number.parseInt(i[2]);if(a==s.start&&l==s.stop)if(n.file2){r=[];for(let e=5;e<i.length;e++){const t=i[e];if(!t)continue;const n=Number.parseInt(t);Number.isNaN(n)||(n<=0||r.push({i:e-5,readcount:n}))}}else{const s=JSON.parse(i[5]);r=Dn(s,e,t,n)}}}),0==r.length)throw"no sample passing filters";const o={};if(n.listsamples){const e=r.map((e=>{const t={readcount:e.readcount};return e.anno?t.sample_name=e.anno.sample_name:t.i=e.i,t}));e.sort(((e,t)=>t.readcount-e.readcount)),e.length>100?(o.samples=e.slice(0,100),o.sampletotalnumber=e.length):o.samples=e}else if(n.singlejunctionsummary&&n.singlejunctionsummary.readcountboxplotpercohort){o.readcountboxplotpercohort=[];for(const e of n.singlejunctionsummary.readcountboxplotpercohort.groups){const t=new Map;for(const n of r){if(!n.anno)continue;const s=n.anno[e.key];null!=s&&(t.has(s)||t.set(s,[]),t.get(s).push(n))}if(0==t.size)continue;const n=[...t].sort(((e,t)=>t[1].length-e[1].length)),s=[];for(const[e,t]of n){let n=t[0].readcount,r=n;t.forEach((e=>{n=Math.min(n,e.readcount),r=Math.max(r,e.readcount)}));const o=Ln(t,.05,.25,.5,.75,.95);s.push({label:e,samplecount:t.length,percentile:{p05:o[0],p25:o[1],p50:o[2],p75:o[3],p95:o[4]},minvalue:n,maxvalue:r})}o.readcountboxplotpercohort.push({label:e.label,boxplots:s})}}return o}(e,t,n);if(e.readcountByjBsamples)return await async function(e,t,n){if(!e.junctionAposlst)throw".junctionAposlst[] missing";let s,r=e.junctionB.start,o=e.junctionB.stop;e.junctionAposlst.forEach((e=>{r=Math.min(r,e[0]),o=Math.max(o,e[1])}));let i=[];if(await F.UE({args:[n.file||n.url,e.junctionB.chr+":"+r+"-"+o],dir:n.dir,callback:t=>{const n=t.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]);if(r==e.junctionB.start&&o==e.junctionB.stop)s=JSON.parse(n[5]);else for(const[t,s]of e.junctionAposlst)if(t==r&&s==o){const e=JSON.parse(n[5]);e.start=r,e.stop=o,i.push(e);break}}}),!s)throw"jB not found";if(0==i.length)throw"none of jA is found";const a=Dn(s,e,t,n);if(0==a.length)throw"no sample passing filters for junctionB";const l=new Set;a.forEach((e=>l.add(e.i)));const c=[];for(const t of i){const n=[];for(const s of t.samples)l.has(s.i)&&(e.readcountCutoff&&s.readcount<e.readcountCutoff||n.push(s));c.push({start:t.start,stop:t.stop,v:Math.floor(Ln(n,.5))})}return{lst:c}}(e,t,n);const s={};if(e.iscustom&&e.getsamples){const e=await F.ZD($n(n),n.dir);if(e[0]){const t=e[0].split("\t");t.length>5&&(s.sample2client=t.slice(5))}}if(!e.rglst)throw"rglst missing";if(n.viewrangeupperlimit){if(e.rglst.reduce(((e,t)=>e+t.stop-t.start),0)>=n.viewrangeupperlimit)throw"zoom in under "+common.bplen(n.viewrangeupperlimit)+" to view details"}let r=0,o=0;const i=[],a=new Set,l=new Set;for(const s of e.rglst)await F.UE({args:[$n(n),s.chr+":"+s.start+"-"+s.stop],dir:n.dir,callback:c=>{const f=c.split("\t"),u=Number.parseInt(f[1]),d=Number.parseInt(f[2]);if(n.file2){f[3];const t=f[4];let n;if("known"==t)n="canonical";else{if("novel"!=t)throw"unknown rnapeg type: "+t;n=Fn}if(e.infoFilter&&e.infoFilter.type&&e.infoFilter.type[n])return;const a={chr:s.chr,start:u,stop:d,info:{type:{lst:[{attrValue:n}]}}},l=[];for(let e=5;e<f.length;e++){const t=f[e];if(!t)continue;const n=Number.parseInt(t);Number.isNaN(n)||(n<=0||(l.push({readcount:n}),r=Math.max(r,n)))}if(0==l.length)return;if(o++,a.sampleCount=l.length,1==a.sampleCount)a.medianReadCount=l[0].readcount;else{const e=Ln(l,.05,.25,.5,.75,.95);a.medianReadCount=e[2],a.readcountBoxplot={percentile:e}}i.push(a)}else{f[3],f[4];if(!(u>=s.start&&u<=s.stop||d>=s.start&&d<=s.stop))return;o++;const c={chr:s.chr,start:u,stop:d,info:{type:{lst:[]}}},p=JSON.parse(f[5]);if(p.sv){c.sv=p.sv;const e=c.chr+"."+c.start+"."+c.sv.mate.chr+"."+c.sv.mate.start;if(a.has(e))return;a.add(e),a.add(c.sv.mate.chr+"."+c.sv.mate.start+"."+c.chr+"."+c.start)}if(p.canonical&&c.info.type.lst.push({attrValue:"canonical"}),p.events)for(const e in p.events){const t=p.events[e];t.__ek=e,c.info.type.lst.push(t)}else p.canonical||c.info.type.lst.push({attrValue:Fn});if(e.infoFilter&&e.infoFilter.type)for(const t of c.info.type.lst)if(e.infoFilter.type[t.attrValue])return;const m=Dn(p,e,t,n);if(0==m.length)return;if((p.exonleft||p.exonright||p.exonleftin||p.exonrightin||p.intronleft||p.intronright||p.leftout||p.rightout)&&(c.ongene={},p.exonleft&&(c.ongene.exonleft=p.exonleft),p.exonright&&(c.ongene.exonright=p.exonright),p.exonleftin&&(c.ongene.exonleftin=p.exonleftin),p.exonrightin&&(c.ongene.exonrightin=p.exonrightin),p.intronleft&&(c.ongene.intronleft=p.intronleft),p.intronright&&(c.ongene.intronright=p.intronright),p.leftout&&(c.ongene.leftout=p.leftout),p.rightout&&(c.ongene.rightout=p.rightout)),m.forEach((e=>{l.add(e.i),r=Math.max(r,e.readcount)})),c.sampleCount=m.length,1==c.sampleCount)c.medianReadCount=m[0].readcount;else{const e=Ln(m,.05,.25,.5,.75,.95);c.medianReadCount=e[2],c.readcountBoxplot={percentile:e}}i.push(c)}}});s.lst=i,s.maxreadcount=r,s.junctiontotalnumber=o,l.size;return s}(s,o,i);n.send(a)}catch(e){e.stack&&console.log(e.stack),n.send({error:e.message||e})}}}(Pr)),Jr.post(Hr+"/mdscnv",(function(e,t){const[n,s,o,i]=so(e.query);if(n)return t.send({error:n});if(!e.query.rglst)return t.send({error:"rglst missing"});if(!e.query.gain)return t.send({error:".gain missing"});if(!e.query.loss)return t.send({error:".loss missing"});if(i.viewrangeupperlimit){if(e.query.rglst.reduce(((e,t)=>e+t.stop-t.start),0)>=i.viewrangeupperlimit)return t.send({error:"zoom in under "+$.bplen(i.viewrangeupperlimit)+" to view details"})}if(e.query.permanentHierarchy){const n=function(e,t){if(!t.cohort)return".cohort missing from ds";if(!t.cohort.hierarchies)return".hierarchies missing from ds.cohort";if(!t.cohort.hierarchies.lst)return".hierarchies.lst[] missing from ds.cohort";const n=t.cohort.hierarchies.lst.find((t=>t.name==e.permanentHierarchy.hierarchyname));if(!n)return"unknown hierarchy "+e.permanentHierarchy.hierarchyname;if(!n.levels)return".levels[] missing in hierarchy "+n.name;const s=n.levels[e.permanentHierarchy.levelidx];if(!s)return"level not found by array idx "+e.permanentHierarchy.levelidx;const r=s.k;return delete e.cohortHiddenAttr,e.cohortOnlyAttr={},e.cohortOnlyAttr[r]={},e.cohortOnlyAttr[r][e.permanentHierarchy.valuekey]=1,null}(e.query,o);if(n)return t.send({error:"permanentHierarchy error: "+n})}const a=[],l={count:0,samples:new Set},c={count:0,samples:new Set};for(const t of e.query.rglst){const n=new Promise(((n,s)=>{const a=(0,x.spawn)(Gr,[i.file?y().join(r().tpmasterdir,i.file):i.url,t.chr+":"+t.start+"-"+t.stop],{cwd:i.usedir}),f=I().createInterface({input:a.stdout}),u=(t.stop-t.start)/t.width,d=[];for(let e=0;e<t.width;e++)d.push({positive:0,negative:0});f.on("line",(n=>{const s=n.split("\t"),r=Number.parseInt(s[1]),i=Number.parseInt(s[2]);if(e.query.bplengthUpperLimit&&i-r>e.query.bplengthUpperLimit)return;const a=JSON.parse(s[3]);if(e.query.valueCutoff&&Math.abs(a.value)<e.query.valueCutoff)return;if(a.sample&&o.cohort&&o.cohort.annotation){const t=o.cohort.annotation[a.sample];if(!t)return;if(e.query.cohortOnlyAttr&&o.cohort&&o.cohort.annotation){let n=!1;for(const s in e.query.cohortOnlyAttr){const r=t[s];if(r&&e.query.cohortOnlyAttr[s][r]){n=!0;break}}if(!n)return}if(e.query.cohortHiddenAttr&&o.cohort.attributes){let n=!1;for(const s in e.query.cohortHiddenAttr){o.cohort.attributes.lst.find((e=>e.key==s)).isNumeric;const r=t[s];if(r){if(e.query.cohortHiddenAttr[s][r]){n=!0;break}}else if(e.query.cohortHiddenAttr[s][Ur]){n=!0;break}}if(n)return}}a.value>0?(l.count++,l.samples.add(a.sample)):a.value<0&&(c.count++,c.samples.add(a.sample));const f=Math.max(t.start,r),p=Math.min(t.stop,i);let m,h;t.reverse?(m=Math.floor((t.stop-p)/u),h=Math.floor((t.stop-f)/u)):(m=Math.floor((f-t.start)/u),h=Math.floor((p-t.start)/u));for(let e=m;e<h;e++)a.value>0?d[e].positive++:a.value<0&&d[e].negative++}));const p=[];a.stderr.on("data",(e=>p.push(e))),a.on("close",(e=>{const t=p.join("");!t||Dr(t)?n(d):s(t)}))}));a.push(n)}Promise.all(a).then((n=>{const s=e.query.rglst.reduce(((t,n)=>t+n.width+e.query.regionspace),0)-e.query.regionspace,r=(0,S.createCanvas)(s,e.query.gain.barheight+e.query.loss.barheight),a=r.getContext("2d"),f={gain:{count:l.count,samplenumber:l.samples.size},loss:{count:c.count,samplenumber:c.samples.size},maxvalue:0};if(l.count+c.count==0)return a.font="15px Arial",a.fillStyle="#aaa",a.textAlign="center",a.textBaseline="middle",a.fillText("No data in view range",s/2,e.query.gain.barheight),f.src=r.toDataURL(),void t.send(f);for(const e of n)for(const t of e)f.maxvalue=Math.max(f.maxvalue,t.positive,t.negative);const u=e.query.maxvalue||f.maxvalue;let d=0;for(const t of n){for(const n of t){if(n.positive){a.fillStyle=e.query.gain.color||"#67a9cf";const t=Math.ceil(e.query.gain.barheight*Math.min(u,n.positive)/u),s=e.query.gain.barheight-t;a.fillRect(d,s,1,t)}if(n.negative){a.fillStyle=e.query.loss.color||"#ef8a62";const t=Math.ceil(e.query.loss.barheight*Math.min(u,n.negative)/u),s=e.query.gain.barheight;a.fillRect(d,s,1,t)}d++}d+=e.query.regionspace}if(f.src=r.toDataURL(),l.samples.size||c.samples.size){const e=new Set([...l.samples,...c.samples]),[t,n]=function(e,t,n){if(!e.cohort||!e.cohort.annotation||0==n.length)return[null,null];const s=[];for(const t of n){const n=e.cohort.annotation[t];n&&s.push(n)}if(0==s.length)return[null,null];let r,o;if(e.cohort.attributes){r=[];for(const n of e.cohort.attributes.lst){const o={label:n.label,key:n.key};if(n.isNumeric){o.isNumeric=!0;continue}const i=new Map;let a=0;for(const t of s){const s=t[n.key];null!=s?(i.has(s)||i.set(s,new Set),i.get(s).add(t[e.cohort.samplenamekey])):a++}const l=[...i];a&&l.push([Ur,a]),l.sort(((e,t)=>t[1]-e[1])),o.values=[];for(const[e,s]of l){const r={name:e,sampleset:s};if(n.values&&n.values[e])for(const t in n.values[e])r[t]=n.values[e][t];t.attributeSummary&&t.attributeSummary[n.key]&&t.attributeSummary[n.key][e]&&(r.totalCount=t.attributeSummary[n.key][e]),o.values.push(r)}r.push(o)}}if(e.cohort.hierarchies){o={};for(const n of e.cohort.hierarchies.lst){const r=he()((0,A.N)(s,n.levels));r.sum((e=>e.value));const i=[];r.eachBefore((s=>{const r={id:s.data.id,name:s.data.name,label:s.data.full,depth:s.depth};if(s.data.lst){r.sampleset=new Set;for(const t of s.data.lst)r.sampleset.add(t[e.cohort.samplenamekey])}s.children||(r.isleaf=1),t.hierarchySummary&&t.hierarchySummary[n.name]&&(r.totalCount=t.hierarchySummary[n.name][s.id]),i.push(r)})),o[n.name]=i}}return[r,o]}(o,i,[...e]);if(t){for(const e of t)for(const t of e.values){t.gain=0,t.loss=0;for(const e of t.sampleset)l.samples.has(e)&&t.gain++,c.samples.has(e)&&t.loss++;delete t.sampleset}f.attributeSummary=t}if(n){for(const e in n)for(const t of n[e])if(t.sampleset){t.gain=0,t.loss=0;for(const e of t.sampleset)l.samples.has(e)&&t.gain++,c.samples.has(e)&&t.loss++}f.hierarchySummary=n}}t.send(f)})).catch((e=>{t.send({error:e}),e.stack&&console.error(e.stack)}))})),Jr.post(Hr+"/mdssvcnv",(async function(e,t){let n,s,o,i,a,l,c,f,u;if(e.query.iscustom){if(n=Pr[e.query.genome],!n)return t.send({error:"invalid genome"});if(s={},o={iscustom:1,file:e.query.file,url:e.query.url,indexURL:e.query.indexURL,allow_getallsamples:!0},e.query.checkexpressionrank){if(!e.query.checkexpressionrank.file&&!e.query.checkexpressionrank.url)return t.send({error:"no file or url for checkexpressionrank"});o.checkexpressionrank={file:e.query.checkexpressionrank.file,url:e.query.checkexpressionrank.url,indexURL:e.query.checkexpressionrank.indexURL}}if(e.query.checkvcf){let n;try{n=JSON.parse(e.query.checkvcf)}catch(e){return t.send({error:"invalid JSON for VCF object"})}if(!n.file&&!n.url)return t.send({error:"no file or url for custom VCF track"});n.type=$.mdsvcftype.vcf,o.checkvcf={info:n.info,tracks:[n]}}if(e.query.checkrnabam){if(!e.query.checkrnabam.samples)return t.send({error:"samples{} missing from checkrnabam"});let n=0;for(const t in e.query.checkrnabam.samples)n++;if(n>13)return t.send({error:"no more than 13 BAM files allowed"});const s=uo(e.query.checkrnabam);if(s)return t.send({error:s});o.checkrnabam=e.query.checkrnabam}}else{if(n=Pr[e.query.genome],!n)return t.send({error:"invalid genome"});if(!n.datasets)return t.send({error:"genome is not equipped with datasets"});if(s=n.datasets[e.query.dslabel],!s)return t.send({error:"invalid dslabel"});if(e.query.getsample4disco)return function(e,t,n,s){if(e.query.iscustom)return t.send({error:"not for custom track"});if(!s.singlesamplemutationjson)return t.send({error:"singlesamplemutationjson not available for this dataset"});const o=e.query.getsample4disco,i=s.singlesamplemutationjson.samples[o];if(!i)return t.send({error:"no data"});const a=y().join(r().tpmasterdir,i);h().readFile(a,{encoding:"utf8"},((e,n)=>{if(e)return t.send({error:"error getting data for this sample"});t.send({text:n})}))}(e,t,0,s);if(e.query.gettrack4singlesample)return function(e,t,n){const s=e.query.gettrack4singlesample;if(e.query.iscustom)return t.send({error:"no server-side config available for custom track"});if(!n.sampleAssayTrack)return t.send({});return t.send({tracks:n.sampleAssayTrack.samples.get(s)})}(e,t,s);if(e.query.findsamplename)return function(e,t,n){if(e.query.iscustom)return t.send({error:"cannot search sample by name in custom track"});const s=e.query.findsamplename.toLowerCase(),r=[];if(!n.cohort.__samplelst){n.cohort.__samplelst=[];for(const e in n.cohort.annotation)n.cohort.__samplelst.push({name:e,low:e.toLowerCase()})}o(n.cohort.__samplelst);for(const e in n.queries){const t=n.queries[e];if(t.type==$.tkt.mdssvcnv&&t.groupsamplebyattr)for(const e of r){const s=n.cohort.annotation[e.name];if(!s)continue;const r=[];for(const e of t.groupsamplebyattr.attrlst){const t=s[e.k];t&&r.push({k:e.k,kvalue:t})}r.length&&(e.attributes=r,e.grouplabel=r.map((e=>e.kvalue)).join(t.groupsamplebyattr.attrnamespacer))}}if(n.cohort&&n.cohort.sampleAttribute&&n.cohort.sampleAttribute.attributes&&n.cohort.annotation)for(const e of r){const t=n.cohort.annotation[e.name];if(!t)continue;const s=[];for(const e in n.cohort.sampleAttribute.attributes){if(n.cohort.sampleAttribute.attributes[e].clientnoshow)continue;const r=t[e];null!=r&&s.push({k:e,v:r})}s.length&&(e.attr=s)}if(n.sampleAssayTrack)for(const e of r){const t=n.sampleAssayTrack.samples.get(e.name);t&&(e.num_assay_tracks=t.length)}if(n.cohort&&n.cohort.mutation_signature)for(const e in n.cohort.mutation_signature.sets){const t=n.cohort.mutation_signature.sets[e];if(t.samples)for(const e of r)t.samples.map.has(e.name)&&(e.mutation_signature=1)}if(n.singlesamplemutationjson)for(const e of r)n.singlesamplemutationjson.samples[e.name]&&(e.disco=1);return t.send({result:r});function o(e){for(const t of e){if(r.length>10)return;-1!=t.low.indexOf(s)&&(r.find((e=>e.name==t.name))||r.push(t))}}}(e,t,s);if(e.query.assaymap)return async function(e,t,n){try{if(!n.assayAvailability)throw"assay availability not enabled for this dataset";const s=new Set(e.query.skip_termids||[]),r=new Map;for(const t in n.cohort.annotation){if(e.query.key){if(n.cohort.annotation[t][e.query.key]!=e.query.value)continue}r.set(t,new Map)}for(const[e,t]of r){const r=n.assayAvailability.samples.get(e);if(r)for(const e of n.assayAvailability.assays)s.has(e.id)||r[e.id]&&t.set(e.id,"yes")}for(const e of r.keys())0==r.get(e).size&&r.delete(e);const o={};o.totalsample=r.size,o.terms=kr({sample2term:r,terms:n.assayAvailability.assays,config:{termidorder:e.query.termidorder}}),t.send(o)}catch(e){t.send({error:e.message||e})}}(e,t,s);if(!s.queries)return t.send({error:"dataset is not equipped with queries"});if(o=s.queries[e.query.querykey],!o)return t.send({error:"invalid querykey"})}if(e.query.getexpression4gene)return async function(e,t,n,s,o){try{const n=e.query.getexpression4gene;if(!n.chr)throw"chr missing";if(!Number.isFinite(n.start))throw"invalid start pos";if(!Number.isFinite(n.stop))throw"invalid stop pos";if(!n.name)throw"unknown gene name";if(o.checkrnabam){const s=Pr[e.query.genome],r=s.tracks.find((e=>e.__isgene)),i=(await go(s,r,n.chr,n.start,n.stop)).get(n.name);if(!i)throw"no gene matching with "+n.name;const a={};await ro(new Map([[n.name,i]]),n.chr,n.start,n.stop,o,a);const l={};for(const e of a.checkrnabam)if(e.genes){const t=e.genes.find((e=>e.gene==n.name));t&&(l[e.sample]=t)}return void t.send({sample2rnabam:l})}let i;if(o.iscustom?i=o.checkexpressionrank:o.expressionrank_querykey&&(i=s.queries[o.expressionrank_querykey]),!i)throw"missing expression data source";const a=i.file?null:await F.d1(i.url,i.indexURL),l=[];await F.UE({args:[i.file?y().join(r().tpmasterdir,i.file):i.url,n.chr+":"+n.start+"-"+n.stop],dir:a,callback:e=>{const t=e.split("\t");let s;try{s=JSON.parse(t[3])}catch(e){reject("invalid json from expression data")}s.sample&&s.gene&&Number.isFinite(s.value)&&(delete s.outlier,s.gene.toLowerCase()==n.name.toLowerCase()&&l.push(s))}});const c=function(e,t,n){const s={};if(e&&e.cohort&&e.cohort.annotation&&t.groupsamplebyattr&&t.groupsamplebyattr.attrlst){const r=new Map;for(const s of n){const n=e.cohort.annotation[s.sample];if(!n)continue;const o=[];for(const e of t.groupsamplebyattr.attrlst)o.push(n[e.k]);const i=o.join(",");r.has(i)||r.set(i,[]),r.get(i).push(s)}for(const e of r.values()){e.sort(((e,t)=>e.value-t.value));for(const t of e)t.rank=vo(t.value,e),s[t.sample]=t}}else{n.sort(((e,t)=>e.value-t.value));for(const e of n)e.rank=vo(e.value,n),s[e.sample]=e}return s}(s,o,l);t.send({sample2rank:c})}catch(e){e.stack&&console.error(e.stack),t.send({error:e.message||e})}}(e,t,0,s,o);if(e.query.ifsamplehasvcf)return function(e,t,n,s,r){if(e.query.iscustom)return t.send({no:1});if(!r.vcf_querykey)return t.send({yes:1});const o=s.queries[r.vcf_querykey];if(!o)return t.send({error:"vcf query missing"});t.send(o.singlesamples?{yes:1}:{no:1})}(e,t,0,s,o);if(!e.query.rglst)return t.send({error:"rglst missing"});if(o.viewrangeupperlimit){if(e.query.rglst.reduce(((e,t)=>e+t.stop-t.start),0)>=o.viewrangeupperlimit)return t.send({error:"zoom in under "+$.bplen(o.viewrangeupperlimit)+" to view details"})}e.query.hiddendt&&(i=new Set(e.query.hiddendt));if(e.query.hiddenmattr){a={};for(const t in e.query.hiddenmattr)a[t]=new Set(e.query.hiddenmattr[t])}if(e.query.filteralleleattr){l={};for(const t in e.query.filteralleleattr){const n=e.query.filteralleleattr[t];n.cutoffvalue,l[t]=n}}if(e.query.filterlocusattr){c={};for(const t in e.query.filterlocusattr){const n=e.query.filterlocusattr[t];n.cutoffvalue,c[t]=n}}if(e.query.sampleset){const t=new Set,n=new Map;for(const s of e.query.sampleset)for(const e of s.samples)t.add(e),n.set(e,s.name);t.size&&(f={set:t,sample2group:n})}if(e.query.hiddensampleattr){u={};for(const t in e.query.hiddensampleattr)u[t]=new Set(e.query.hiddensampleattr[t])}if(o.url)try{o.dir=await F.d1(o.url,o.indexURL)}catch(e){return t.send({error:"svcnv file index url error"})}const d=await function(e,t,n,s,o,i,a){if(!t.file&&!t.url)return[];const l=[];for(const c of n.query.rglst){const f=new Promise(((l,f)=>{const u=[],d=(0,x.spawn)(Gr,[t.file?y().join(r().tpmasterdir,t.file):t.url,c.chr+":"+c.start+"-"+c.stop],{cwd:t.dir});I().createInterface({input:d.stdout}).on("line",(t=>{const r=t.split("\t"),l=Number.parseInt(r[1]),c=Number.parseInt(r[2]);let 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t of e.lst){const e=r.get(t.sampleobj.name);if(e){const n=o(e);t.sampleobj.color=n,i.has(e)||i.set(e,{count:0,color:n,label:e}),i.get(e).count++}else a++,t.sampleobj.color=fr}if(s.categories=[],t.CTE1&&t.CTE1.name2bin)for(const e of t.CTE1.name2bin.keys()){const t=i.get(e);t&&s.categories.push(t)}else for(const[e,t]of i)s.categories.push(t);a&&s.categories.push({count:a,color:fr,label:"Unannotated"})}}catch(e){s.error=e.message||e,e.stack&&console.log(e.stack)}}(s,0,r,o),s.trigger_vcfbyrange&&(await sr(s,0,r,o),s.trigger_ld)){o.__mposset=new Set;for(const e of o.vcf.rglst)if(e.variants)for(const t of e.variants)o.__mposset.add(t.pos)}if(s.trigger_ld){o.ld={};for(const e of s.trigger_ld.tracks)await dr(e,s,0,r,o);delete o.__mposset}s.trigger_ssid_onevcfm&&await async function(e,t,n,s){if(n.iscustom)throw"custom ds not allowed";const r=n.track.vcf;if(!r)throw"ds.track.vcf missing";if(!e.m)throw"q.m missing";const o=(r.nochr?e.m.chr.replace("chr",""):e.m.chr)+":"+(e.m.pos+1)+"-"+(e.m.pos+1),i=r.chr2bcffile[e.m.chr];if(!i)throw"chr not in chr2bcffile";let a;if(await F.UE({isbcf:!0,args:["query",i,"-r",o,"-f",nr+"\t%FORMAT\n"],dir:r.dir,callback:t=>{const[n,s,o]=D.S(t,r);for(const t of s)if(t.pos==e.m.pos&&t.ref==e.m.ref&&t.alt==e.m.alt)return void(a=t)}}),!a)throw"variant not found";const l=[],c=[],f=[];for(const t of a.sampledata){if(!t.genotype)continue;const n=-1!=t.genotype.indexOf(e.m.ref),s=-1!=t.genotype.indexOf(e.m.alt);n?s?c.push(t.sampleobj.name):l.push(t.sampleobj.name):s&&f.push(t.sampleobj.name)}const u=Math.random().toString();s.ssid=u,s.groups={};const d=[];if(l.length){const e="Homozygous reference";s.groups[e]={size:l.length},d.push(e+"\t"+l.join(","))}if(c.length){const e="Heterozygous";s.groups[e]={size:c.length},d.push(e+"\t"+c.join(","))}if(f.length){const e="Homozygous alternative";s.groups[e]={size:f.length},d.push(e+"\t"+f.join(","))}await F.Sf(y().join(tr.cachedir_ssid,u),d.join("\n"))}(s,0,r,o),s.trigger_getvcfcsq&&await async function(e,t,n,s){const r=n.track.vcf;if(!r)throw"ds.track.vcf missing";if(!e.m)throw"q.m missing";const o=(r.nochr?e.m.chr.replace("chr",""):e.m.chr)+":"+(e.m.pos+1)+"-"+(e.m.pos+1),i=r.chr2bcffile[e.m.chr];if(!i)throw"chr not in chr2bcffile";await F.UE({isbcf:!0,args:["query",i,"-r",o,"-f",nr+"\\n"],dir:r.dir,callback:t=>{const[n,o,i]=D.S(t,r);for(const t of o)if(t.pos==e.m.pos&&t.ref==e.m.ref&&t.alt==e.m.alt)return void(s.csq=t.csq)}})}(s,0,r,o),n.send(o)}catch(e){n.send({error:e.message||e}),e.stack&&console.log(e.stack)}}}(Pr)),Jr.post(Hr+"/mdsexpressionrank",(function(e,t){let n,s,o,i=new Set;Promise.resolve().then((()=>{if(!e.query.rglst)throw"rglst missing";if(e.query.rglst.reduce(((e,t)=>e+t.stop-t.start),0)>1e7)throw"Zoom in below 10 Mb to show expression rank";if(!e.query.sample)throw"sample missing";if(e.query.iscustom){if(n=Pr[e.query.genome],!n)throw"invalid genome";if(!e.query.file&&!e.query.url)throw"no file or url for expression data";s={},o={file:e.query.file,url:e.query.url,indexURL:e.query.indexURL}}else{const[t,r,i,a]=so(e.query);if(t)throw t;if(n=r,s=i,o=a,!o.samples)throw"total samples missing from server config";if(-1==o.samples.indexOf(e.query.sample))throw{nodata:1}}if(o.viewrangeupperlimit&&e.query.rglst.reduce(((e,t)=>e+t.stop-t.start),0)>o.viewrangeupperlimit)throw"zoom in under "+$.bplen(o.viewrangeupperlimit)+" to view data";if(e.query.levelkey){if(!e.query.levelvalue)throw"levelvalue is required when levelkey is used";if(!s.cohort||!s.cohort.annotation)throw".cohort.annotation missing from dataset"}if(!o.file){if(!o.url)throw"file or url missing";return F.d1(o.url,o.indexURL)}})).then((t=>{const n=[];for(const a of e.query.rglst)n.push(new Promise(((n,l)=>{const c=(0,x.spawn)(Gr,[o.file?y().join(r().tpmasterdir,o.file):o.url,a.chr+":"+a.start+"-"+a.stop],{cwd:t}),f=I().createInterface({input:c.stdout}),u=new Map;f.on("line",(t=>{const n=t.split("\t"),r=JSON.parse(n[3]);if(!r.gene)return;if(!r.sample)return;if(!Number.isFinite(r.value))return;const o=n[0],a=Number.parseInt(n[1]),l=Number.parseInt(n[2]);if(r.sample==e.query.sample)return u.has(r.gene)||u.set(r.gene,{chr:o,start:a,stop:l,allvalues:[]}),u.get(r.gene).thisvalue=r.value,void(r.ase&&(u.get(r.gene).ase=r.ase));if(e.query.attributes){const t=s.cohort.annotation[r.sample];if(!t)return;for(const n of e.query.attributes)if(n.k&&n.kvalue&&n.kvalue!=t[n.k])return}i.add(r.sample),u.has(r.gene)||u.set(r.gene,{chr:o,start:a,stop:l,allvalues:[]}),u.get(r.gene).allvalues.push({value:r.value})}));const d=[];c.stderr.on("data",(e=>d.push(e))),c.on("close",(e=>{const t=d.join("");t&&!Dr(t)&&l({message:t}),n(u)}))})));return Promise.all(n)})).then((e=>{const n=[];for(const t of e)for(const[e,s]of t)null!=s.thisvalue&&(s.allvalues.sort(((e,t)=>e.value-t.value)),s.rank=vo(s.thisvalue,s.allvalues),delete s.allvalues,s.gene=e,n.push(s));t.send({result:n,samplecount:i.size})})).catch((e=>{e.stack&&console.log(e),e.nodata?t.send({nodata:1}):t.send({error:e.message?e.message:e})}))})),Jr.post(Hr+"/mdsgeneboxplot",(e=>async(t,n)=>{try{const[s,o,i,a]=function(e,t){if(!t.query.gene)throw"gene name missing";if(!t.query.chr)throw"chr missing";if(!Number.isInteger(t.query.start))throw"start missing";if(!Number.isInteger(t.query.stop))throw"stop missing";const n=e[t.query.genome];if(!n)throw"invalid genome";let s,r,o;if(t.query.iscustom){if(!t.query.file&&!t.query.url)throw"no file or url for expression data";s={},r={file:t.query.file,url:t.query.url,indexURL:t.query.indexURL}}else{if(!n.datasets)throw"genome is not equipped with datasets";if(!t.query.dslabel)throw"dslabel missing";if(s=n.datasets[t.query.dslabel],!s)throw"invalid dslabel";if(!s.queries)throw"dataset is not equipped with queries";if(!t.query.querykey)throw"querykey missing";if(r=s.queries[t.query.querykey],!r)throw"invalid querykey"}if(t.query.svcnv)if(o={},t.query.iscustom)o.dsquery={file:t.query.svcnv.file,url:t.query.svcnv.url,indexURL:t.query.svcnv.indexURL};else{t.query.svcnv.genome=t.query.genome;const e=n.datasets[t.query.svcnv.dslabel];if(!e)throw"invalid dslabel";if(!e.queries)throw"dataset is not equipped with queries";if(!t.query.svcnv.querykey)throw"querykey missing";const s=e.queries[t.query.svcnv.querykey];if(!s)throw"invalid querykey";o.ds=e,o.dsquery=s}if(t.query.getgroup)if(t.query.sampleset);else{if(!s.cohort||!s.cohort.annotation)throw"no sample annotation for getting group";if(t.query.getgroup_unannotated){if(!r.boxplotbysamplegroup)throw"dsquery.boxplotbysamplegroup{} missing when getgroup_unannotated"}else{if(!Array.isArray(t.query.getgroup))throw"getgroup should be array";for(const e of t.query.getgroup){if(!e.k)throw"k missing from one of getgroup";if(!e.kvalue)throw"kvalue missing from one of getgroup"}}}return[n,s,r,o]}(e,t);t.query.getalllst,n.send(await async function(e,t,n,s,o){n.url&&(n.dir=await F.d1(n.url,n.indexURL));s&&s.dsquery.url&&(s.dsquery.dir=await F.d1(s.dsquery.url,s.dsquery.indexURL));const i=function(e){if(!e.query.sampleset)return;const t=new Map;for(const n of e.query.sampleset)for(const e of n.samples)t.set(e,n.name);return t}(o),a=new Map,l=[],c=[];if(await F.UE({args:[n.file?y().join(r().tpmasterdir,n.file):n.url,o.query.chr+":"+o.query.start+"-"+o.query.stop],dir:n.dir,callback:e=>{const s=e.split("\t"),r=JSON.parse(s[3]);if(r.gene&&r.gene==o.query.gene&&Number.isFinite(r.value))if(o.query.getalllst)l.push({sample:r.sample,value:r.value});else if(o.query.getgroup){if(!r.sample)return;if(i)return void(o.query.getgroup_unannotated?i.has(r.sample)||c.push(r):i.get(r.sample)==o.query.getgroup[0].full&&c.push(r));const e=t.cohort.annotation[r.sample];if(o.query.getgroup_unannotated){if(!e)return void c.push(r);for(const t of n.boxplotbysamplegroup.attributes)if(null==e[t.k])return void c.push(r);return}if(!e)return;for(const t of o.query.getgroup)if(t.kvalue!=e[t.k])return;c.push(r)}else if(n.boxplotbysamplegroup&&t.cohort&&t.cohort.annotation){if(!r.sample)return;let e;e=null==o.query.index_boxplotgroupers||0==o.query.index_boxplotgroupers?n.boxplotbysamplegroup.attributes:n.boxplotbysamplegroup.additionals[o.query.index_boxplotgroupers-1].attributes;const s=t.cohort.annotation[r.sample];if(!s)return void l.push({sample:r.sample,value:r.value});const i=s[e[0].k];if(null==i)return void l.push({sample:r.sample,value:r.value});const c=[];for(let t=1;t<e.length;t++){const n=s[e[t].k];if(null==n)break;c.push(n)}c.unshift(i);const f=c.join(", ");if(!a.has(f)){const t={samples:[],attributes:[]};for(const n of e){const e=s[n.k];if(null==e)break;const r={k:n.k,kvalue:e};n.full&&(r.full=n.full,r.fullvalue=s[n.full]),t.attributes.push(r)}a.set(f,t)}a.get(f).samples.push({sample:r.sample,value:r.value})}else if(i){if(!r.sample)return;const e=i.get(r.sample);if(!e)return void l.push({sample:r.sample,value:r.value});a.has(e)||a.set(e,{samples:[],attributes:[{full:e}]}),a.get(e).samples.push({sample:r.sample,value:r.value})}else l.push({sample:r.sample,value:r.value})}}),o.query.getgroup2boxplot){c.sort(((e,t)=>e.value-t.value));const{w1:e,w2:t,p25:n,p50:s,p75:r,out:o}=F.JC(c);return{n:c.length,min:c[0].value,max:c[c.length-1].value,w1:e,w2:t,p25:n,p50:s,p75:r,out:o}}const f=[];for(const[e,t]of a)f.push({name:e,values:t.samples,attributes:t.attributes});l.length&&f.push({name:"Unannotated",values:l});c.length&&f.push({values:c});if(o.query.getalllst)return{lst:f[0].values};if(o.query.iscustom&&!i||1==f.length){if(f[0]){const e=f[0].values;return e.sort(((e,t)=>t.value-e.value)),{lst:e,max:e[0].value,min:e[e.length-1].value}}return{nodata:1}}const u=await async function(e,t){if(!t||!e.query.svcnv.useloss&&!e.query.svcnv.usegain&&!e.query.svcnv.usesv)return;let n=e.query.start,s=e.query.stop;e.query.svcnv.usesv&&Number.isInteger(e.query.svcnv.svflank)&&(n=Math.max(0,n-e.query.svcnv.svflank),s+=e.query.svcnv.svflank);const o=new Map;return await F.UE({args:[t.dsquery.file?y().join(r().tpmasterdir,t.dsquery.file):t.dsquery.url,e.query.chr+":"+n+"-"+s],dir:t.dsquery.dir,callback:t=>{const n=t.split("\t"),s=JSON.parse(n[3]);if(s.sample)if(s.chrA||s.chrB){if(!e.query.svcnv.usesv)return;o.has(s.sample)||o.set(s.sample,{}),o.get(s.sample).sv=1}else{if(!e.query.svcnv.usegain&&!e.query.svcnv.useloss)return;if(e.query.svcnv.usesv&&e.query.svcnv.svflank){const t=Number.parseInt(n[1]),s=Number.parseInt(n[2]);if(Math.max(e.query.start,t)>Math.min(e.query.stop,s))return}if(!Number.isFinite(s.value))return;if(!e.query.svcnv.usegain&&s.value>0)return;if(!e.query.svcnv.useloss&&s.value<0)return;if(e.query.svcnv.valueCutoff&&Math.abs(s.value)<e.query.svcnv.valueCutoff)return;if(e.query.svcnv.bplengthUpperLimit&&Number.parseInt(n[2])-Number.parseInt(n[1])>e.query.svcnv.bplengthUpperLimit)return;o.has(s.sample)||o.set(s.sample,{}),s.value>0?o.get(s.sample).gain=1:s.value<0&&(o.get(s.sample).loss=1)}}}),o}(o,s);if(o.query.getgroup){if(f[0]){const e=f[0].values;if(e.sort(((e,t)=>t.value-e.value)),u)for(const t of e){const e=u.get(t.sample);if(e)for(const n in e)t[n]=e[n]}return{lst:e,max:e[0].value,min:e[e.length-1].value}}return{nodata:1}}const d=[];let p=null,m=null;for(const e of f){e.values.sort(((e,t)=>e.value-t.value));const t=e.values.length;null==p?(p=e.values[0].value,m=e.values[t-1].value):(p=Math.min(p,e.values[0].value),m=Math.max(m,e.values[t-1].value));const{w1:n,w2:s,p25:r,p50:i,p75:a,out:l}=F.JC(e.values),c=[{isall:1,w1:n,w2:s,p25:r,p50:i,p75:a,out:l}];if(u){if(o.query.svcnv.usegain){const t=e.values.filter((e=>u.has(e.sample)&&u.get(e.sample).gain));if(t.length){const{w1:e,w2:n,p25:s,p50:r,p75:o,out:i}=F.JC(t);c.push({iscnvgain:1,samplecount:t.length,w1:e,w2:n,p25:s,p50:r,p75:o,out:i})}}if(o.query.svcnv.useloss){const t=e.values.filter((e=>u.has(e.sample)&&u.get(e.sample).loss));if(t.length){const{w1:e,w2:n,p25:s,p50:r,p75:o,out:i}=F.JC(t);c.push({iscnvloss:1,samplecount:t.length,w1:e,w2:n,p25:s,p50:r,p75:o,out:i})}}if(o.query.svcnv.usesv){const t=e.values.filter((e=>u.has(e.sample)&&u.get(e.sample).sv));if(t.length){const{w1:e,w2:n,p25:s,p50:r,p75:o,out:i}=F.JC(t);c.push({issv:1,samplecount:t.length,w1:e,w2:n,p25:s,p50:r,p75:o,out:i})}}}d.push({name:e.name+" ("+e.values.length+")",boxplots:c,attributes:e.attributes})}return d.sort(((e,t)=>e.name<t.name?-1:e.name>t.name?1:0)),{groups:d,min:p,max:m}}(0,o,i,a,t))}catch(e){e.stack&&console.log(e),n.send({error:e.message||e})}})(Pr)),Jr.post(Hr+"/mdsgenevalueonesample",(async function(e,t){const n=e.query;try{if(!n.sample)throw".sample missing";if(!n.genes)throw".genes[] missing";let s,o,i;if(e.query.iscustom){if(s=Pr[n.genome],!s)throw"invalid genome";if(!n.file&&!n.url)throw"no file or url for expression data";o={},i={file:n.file,url:n.url,indexURL:n.indexURL}}else{const[e,t,r,a]=so(n);if(e)throw e;s=t,o=r,i=a}const a=i.file?null:await F.d1(i.url,i.indexURL),l={};let c=!0;for(const e of n.genes){let t;await F.UE({args:[i.file?y().join(r().tpmasterdir,i.file):i.url,e.chr+":"+e.start+"-"+e.stop],dir:a,callback:s=>{const r=s.split("\t");if(!r[3])return;const o=JSON.parse(r[3]);o.gene==e.gene&&o.sample==n.sample&&(t=o.value)}}),Number.isFinite(t)&&(l[e.gene]=t,c=!1)}c?t.send({nodata:1}):t.send({result:l})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/vcf",(async function(e,t){try{const[n,s,r]=F.ZX(e);if(n)throw n;const o=r?await F.d1(s,e.query.indexURL):null;if(!e.query.rglst)throw"rglst missing";const i=[];for(const t of e.query.rglst)await F.UE({args:[s,t.chr+":"+t.start+"-"+t.stop],dir:o,callback:e=>i.push(e)});t.send({linestr:i.join("\n")})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.get(Hr+"/vcfheader",(async function(e,t){try{if(!e.query.genome)throw"genome missing";const n=Pr[e.query.genome];if(!n)throw"invalid genome";const[s,r,o]=F.ZX(e);if(s)throw s;const i=o?await F.d1(r,e.query.indexURL):null;t.send({metastr:(await F.ZD(r,i)).join("\n"),nochr:await F.Jy(r,i,n)})}catch(e){e.stack&&console.error(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/translategm",(async function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"invalid genome";const s=e.query.gm;if(!s)throw"missing gm{}";if(!s.chr)throw"gm.chr missing";if(!s.start)throw"gm.start missing";if(!Number.isInteger(s.start))throw"gm.start not integer";if(!s.stop)throw"gm.stop missing";if(!Number.isInteger(s.stop))throw"gm.stop not integer";const r=await F.Kf(n,s.chr+":"+(s.start+1)+"-"+s.stop),o=$.fasta2gmframecheck(s,r);t.send({frame:o})}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Jr.post(Hr+"/samplematrix",(function(e,t){Promise.resolve().then((()=>{const t=Pr[e.query.genome];if(!t)throw"invalid genome";let n,s;if(e.query.iscustom){if(!e.query.querykey2tracks)throw"querykey2tracks{} missing for custom dataset";n={queries:{}};for(const t in e.query.querykey2tracks){const s=e.query.querykey2tracks[t];if(!s.type)throw'missing "type" for a data track';if(s.type==$.tkt.mdsvcf){const s=e.query.querykey2tracks[t];s.type=$.mdsvcftype.vcf,n.queries[t]={type:$.tkt.mdsvcf,info:s.info,tracks:[s]}}else if(s.type==$.tkt.mdssvcnv)n.queries[t]=s;else{if(s.type!=$.tkt.mdsexpressionrank)throw"unknown type of data track: "+s.type;n.queries[t]=s}}}else{if(!t.datasets)throw"genome is not equipped with datasets";if(!e.query.dslabel)throw"dslabel missing";if(n=t.datasets[e.query.dslabel],!n)throw"invalid dslabel";if(!n.queries)throw"dataset is not equipped with queries"}if(e.query.sampleset)s=new Set(e.query.sampleset);else if(e.query.limitsamplebyeitherannotation){if(!n.cohort)throw"limitsamplebyeitherannotation but no cohort in ds";if(!n.cohort.annotation)throw"limitsamplebyeitherannotation but no cohort.annotation in ds";s=new Set;for(const t in n.cohort.annotation){const r=n.cohort.annotation[t];for(const n of e.query.limitsamplebyeitherannotation)if(r[n.key]==n.value){s.add(t);break}}}const r=[];for(const t of e.query.features){let e,o=[];if(t.querykey){if(!n.queries)throw"using querykey for a feature but no ds.queries";if(e=n.queries[t.querykey],!e)throw"unknown dsquery by key "+t.querykey}else if(t.querykeylst){if(!n.queries)throw"using querykeylst for a feature but no ds.queries";for(const e of t.querykeylst){const t=n.queries[e];if(!t)throw'unknown key "'+e+'" from querykeylst';o.push(t)}if(0==o.length)throw"no valid keys in querykeylst"}else if(!t.issampleattribute)throw"unknown way to query a feature";if(t.isgenevalue){const[o,i]=_o(t,n,e,s);if(o)throw"error with isgenevalue: "+o;r.push(i)}else if(t.iscnv){const[o,i]=ko(t,n,e,s);if(o)throw"error with iscnv: "+o;r.push(i)}else if(t.isloh){const[o,i]=qo(t,n,e,s);if(o)throw"error with isloh: "+o;r.push(i)}else if(t.isvcf){const[o,i]=Co(t,n,e,s);if(o)throw"error with isvcf: "+o;r.push(i)}else if(t.isitd){const[o,i]=xo(t,n,e,s);if(o)throw"error with isitd: "+o;r.push(i)}else if(t.issvfusion){const[o,i]=No(t,n,e,s);if(o)throw"error with issvfusion: "+o;r.push(i)}else if(t.issvcnv){const[o,i]=So(t,n,e,s);if(o)throw"error with issvcnv: "+o;r.push(i)}else if(t.ismutation){const[e,i]=Ao(t,n,o,s);if(e)throw"error with ismutation: "+e;r.push(i)}else{if(!t.issampleattribute)throw"unknown type of feature";{const[e,o]=wo(t,n,s);if(e)throw"error with issampleattribute: "+e;r.push(o)}}}return Promise.all(r)})).then((e=>{t.send({results:e})})).catch((e=>{t.send({error:"string"==typeof e?e:e.message}),e.stack&&console.error(e.stack)}))})),Jr.get(Hr+"/mdssamplescatterplot",(async function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"invalid genome";const s=n.datasets[e.query.dslabel];if(!s)throw"invalid dataset";if(!s.cohort)throw"no cohort for dataset";if(!s.cohort.annotation)throw"cohort.annotation missing for dataset";const r=s.cohort.scatterplot;if(!r)throw"scatterplot not supported for this dataset";const o=[];for(const t in s.cohort.annotation){const n=s.cohort.annotation[t];if(e.query.subsetkey&&n[e.query.subsetkey]!=e.query.subsetvalue)continue;const i=n[r.x.attribute];if(!Number.isFinite(i))continue;const a=n[r.y.attribute];Number.isFinite(a)&&o.push({sample:t,x:i,y:a,s:n})}t.send({colorbyattributes:r.colorbyattributes,colorbygeneexpression:r.colorbygeneexpression,querykey:r.querykey,dots:o,tracks:r.tracks})}catch(e){e.stack&&console.error(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/mdssamplesignature",(function(e,t){try{const n=e.query;if(!n.sample)throw".sample missing";const s=Pr[n.genome];if(!s)throw"invalid genome";const r=s.datasets[n.dslabel];if(!r)throw"invalid dataset";if(!r.cohort)throw"no cohort for dataset";if(!r.cohort.mutation_signature)throw"no mutation_signature for cohort";const o=[];for(const e in r.cohort.mutation_signature.sets){const t=r.cohort.mutation_signature.sets[e];if(!t.samples)continue;const s=t.samples.map.get(n.sample);if(!s)continue;const i=[];for(const e in t.signatures)s[e]&&i.push({k:e,v:s[e]});i.length&&o.push({key:e,valuename:t.samples.valuename,annotation:i.sort(((e,t)=>t.v-e.v))})}t.send({lst:o})}catch(e){e.stack&&console.error(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/mdssurvivalplot",function(e){return async(t,n)=>{try{const s=t.query,r=e[s.genome];if(!r)throw"invalid genome";const o=r.datasets[s.dslabel];if(!o)throw"invalid dataset";if(!o.cohort)throw"no cohort for dataset";if(!o.cohort.annotation)throw"cohort.annotation missing for dataset";const i=o.cohort.survivalplot;if(!i)throw"survivalplot not supported for this dataset";if(!i.plots)throw".plots{} missing";if(t.query.init)return void n.send(i.init);if(!s.type)throw".type missing";const a=i.plots[s.type];if(!a)throw"unknown plot type: "+s.type;const l=function(e,t,n){if(!e.samplerule)throw".samplerule missing";if(!e.samplerule.full)throw".samplerule.full missing";const s=[];if(e.samplerule.full.byattr){const n=e.samplerule.full.key;if(!n)throw"key missing from samplerule.full{}";const r=e.samplerule.full.value;if(null==r)throw"value missing from samplerule.full{}";for(const e in t.cohort.annotation){const o=t.cohort.annotation[e];o[n]==r&&s.push({name:e,o})}}else if(e.samplerule.full.useall)for(const e in t.cohort.annotation){const n=t.cohort.annotation[e];s.push({name:e,o:n})}else{if(!e.samplerule.full.usesampleset)throw"unknown rule for samplerule.full";{const n=e.samplerule.full.sampleset;for(const e in n){const r=n[e],o=t.cohort.annotation[r];null!=o&&s.push({name:r,o})}}}const r=[];for(const e of s)Number.isFinite(e.o[n.serialtimekey])&&(e.serialtime=e.o[n.serialtimekey],e.censored=e.o[n.iscensoredkey],r.push(e));if(0==r.length)throw"no samples found for full set";return r}(s,o,a),c=await async function(e,t,n,s){if(t.samplerule.mutated_sets){const n=new Set(e.map((e=>e.name))),s=t.samplerule.mutated_sets.reduce(((t,s)=>{const r=new Set(s.samplenames);s.lst=e.filter((e=>r.has(e.name)));for(const e of s.samplenames)n.delete(e);return delete s.samplenames,t.push(s),t}),[]);return s.push({name:"No mutation (n="+n.size+")",lst:e.filter((e=>n.has(e.name))),is_notmutated:!0}),s}const r=t.samplerule.set;if(!r)return[{name:"All",lst:e}];if(r.geneexpression){if(!r.gene)throw".gene missing from samplerule.set";if(!r.chr)throw".chr missing from samplerule.set";if(!Number.isInteger(r.start))throw".start not integer from samplerule.set";if(!Number.isInteger(r.stop))throw".start not integer from samplerule.set";if(r.bymedian)return await async function(e,t,n,s){const r=t.samplerule.set,[o,i]=await Cr(e,t,n),a=Math.ceil(i.length/2),l=i[a-1].genevalue;return[{name:r.gene+" "+o.datatype+" below median (n="+a+", value<"+l+")",lst:i.slice(0,a)},{name:r.gene+" "+o.datatype+" above median (n="+(i.length-a)+", value>="+l+")",lst:i.slice(a,i.length)}]}(e,t,n);if(r.byquartile)return await async function(e,t,n,s){const r=t.samplerule.set,[o,i]=await Cr(e,t,n),a=Math.ceil(.25*i.length),l=Math.ceil(.5*i.length),c=Math.ceil(.75*i.length),f=i[a-1].genevalue,u=i[l-1].genevalue,d=i[c-1].genevalue;return[{name:r.gene+" "+o.datatype+" from 1st quartile (n="+a+", value<"+f+")",lst:i.slice(0,a),isfirstquartile:!0},{name:r.gene+" "+o.datatype+" from 2nd quartile (n="+(l-a)+", "+f+"<=value<"+u+")",lst:i.slice(a,l)},{name:r.gene+" "+o.datatype+" from 3rd quartile (n="+(c-l)+", "+u+"<=value<"+d+")",lst:i.slice(l,c)},{name:r.gene+" "+o.datatype+" from 4th quartile (n="+(i.length-c)+", value>="+d+")",lst:i.slice(c,i.length),isfourthquartile:!0}]}(e,t,n)}if(r.mutation){if(!r.chr)throw".chr missing from samplerule.set";if(!Number.isInteger(r.start))throw".start not integer from samplerule.set";if(!Number.isInteger(r.stop))throw".start not integer from samplerule.set";return await async function(e,t,n){const s=t.samplerule.set;if(s.samples_snvindel=new Set,s.samples_cnv=new Set,s.samples_loh=new Set,s.samples_sv=new Set,s.samples_fusion=new Set,s.samples_itd=new Set,s.cnv&&!s.snvindel&&!s.loh&&!s.sv&&!s.fusion&&!s.itd){const[s,r]=await Nr(e,t,n,!0),o=[],i=[],a=[];for(const t of e)s.has(t.name)?o.push(t):r.has(t.name)?i.push(t):a.push(t);const l=[];return i.length&&l.push({name:"Copy number loss (n="+i.length+")",lst:i}),o.length&&l.push({name:"Copy number gain (n="+o.length+")",lst:o}),a.length&&l.push({name:"No copy number variation (n="+a.length+")",lst:a}),l}const r=await Nr(e,t,n),o=[];for(const t of e)r.find((e=>e.name==t.name))||o.push(t);const i=[];r.length&&i.push({name:"With mutation (n="+r.length+")",lst:r});o.length&&i.push({name:"No mutation (n="+o.length+")",lst:o});return i}(e,t,n)}throw"unknown rule for samplerule.set{}"}(l,s,o);let f;c.length>1&&(f=await xr(c)),await async function(e,t){if(!e.samplerule.mutated_sets)return;const n=t.find((e=>e.is_notmutated));if(!n)return;for(const e of t){if(e.is_notmutated)continue;const t=await xr([e,n]);e.pvalue=t}}(s,c),await async function(e,t){if(!e.samplerule.set)return;if(!e.samplerule.set.geneexpression)return;if(!e.samplerule.set.byquartile)return;if(4!=t.length)return;if(e.samplerule.set.against1st){for(let e=1;e<4;e++)t[e].pvalue=await xr([t[0],t[e]]);return}if(e.samplerule.set.against4th){for(let e=0;e<3;e++)t[e].pvalue=await xr([t[e],t[3]]);return}}(s,c);for(const e of c)jr(e),delete e.lst;const u={samplesets:c,pvalue:f};s.samplerule.set&&s.samplerule.set.mutation&&(u.count_snvindel=s.samplerule.set.samples_snvindel.size,u.count_cnv=s.samplerule.set.samples_cnv.size,u.count_loh=s.samplerule.set.samples_loh.size,u.count_sv=s.samplerule.set.samples_sv.size,u.count_fusion=s.samplerule.set.samples_fusion.size,u.count_itd=s.samplerule.set.samples_itd.size),n.send(u)}catch(e){e.stack&&console.error(e.stack),n.send({error:e.message||e})}}}(Pr)),Jr.post(Hr+"/fimo",function(e){return async(t,n)=>{try{const s=t.query;if(!s.m)throw"no mutation";if(!s.m.chr)throw"mutation chr missing";if(!Number.isInteger(s.m.pos))throw"mutation position is not integer";if(!s.m.ref)throw"mutation ref allele missing";if(!s.m.alt)throw"mutation alt allele missing";const r=e[s.genome];if(!r)throw"invalid genome";if(!r.fimo_motif)throw"motif finding not supported on this genome";const o=await async function(e,t){const n=e.m.pos-e.flankspan,s=e.m.pos+e.flankspan,r=await F.Kf(t,e.m.chr+":"+n+"-"+s);!function(e,t,n){if(!e.m.ref)return;if("-"==e.m.ref)return;const s=n.split("\n").slice(1).join("").toUpperCase(),r=s.substring(e.m.pos-t,e.m.pos-t+e.m.ref.length);if(r==e.m.ref.toUpperCase())return;if(common.reversecompliment(r)==e.m.ref.toUpperCase())e.m.ref=r,"-"!=e.m.alt&&(e.m.alt=common.reversecompliment(e.m.alt))}(e,n,r);const o=await _r(e,t,r),i=new Map;for(const e of o)e.pvalue_ref=e.pvalue,delete e.pvalue,e.logpvalue_ref=e.logpvalue,delete e.logpvalue,i.has(e.name)||i.set(e.name,[]),i.get(e.name).push(e);const a=function(e,t,n,s){const r=s.split("\n"),o=r.slice(1).join("");return r[0]+"\n"+o.substr(0,e.pos-t)+("-"==e.alt?"":e.alt)+o.substr(e.pos-t+("-"==e.ref?0:e.ref.length))}(e.m,n,0,r),l=await _r(e,t,a);for(const e of l){e.pvalue_alt=e.pvalue,delete e.pvalue,e.logpvalue_alt=e.logpvalue,delete e.logpvalue,i.has(e.name)||i.set(e.name,[]);let t=!0;for(const n of i.get(e.name))if(null!=n.logpvalue_ref&&n.strand==e.strand&&Math.abs(e.start-n.start)<=2&&Math.abs(e.stop-n.stop)<=2){n.pvalue_alt=e.pvalue_alt,n.logpvalue_alt=e.logpvalue_alt,n.logpvaluediff=e.logpvalue_alt-n.logpvalue_ref,n.logpvaluediff>0?n.gain=!0:n.loss=!0,t=!1;break}t&&i.get(e.name).push(e)}let c=0,f=0;const u=[];for(const t of i.values())for(const n of t)null==n.logpvaluediff&&(null==n.pvalue_ref?(n.gain=!0,n.logpvaluediff=n.logpvalue_alt):null==n.pvalue_alt&&(n.loss=!0,n.logpvaluediff=-n.logpvalue_ref)),null!=e.minabslogp&&Math.abs(n.logpvaluediff)<e.minabslogp||(n.logpvaluediff>0?c=Math.max(c,n.logpvaluediff):f=Math.min(f,n.logpvaluediff),u.push(n));return{items:u,valuemin:f,valuemax:c,refstart:n,refstop:s,refseq:r.split("\n").slice(1).join("")}}(s,r);n.send(o)}catch(e){e.stack&&console.log(e.stack),n.send({error:e.message||e})}}}(Pr)),Jr.all(Hr+"/termdb",we.TO(Pr)),Jr.all(Hr+"/termdb-barsql",Ae.TO(Pr)),Jr.post(Hr+"/singlecell",function(e){return async(t,n)=>{try{const s=t.query,r=e[s.genome];if(!r)throw"invalid genome";if(s.getpcd)return void await async function(e,t){const n={},s=await async function(e,t){if(!e.textfile)throw".textfile missing";{const[t,n,s]=F.ZX({query:{file:e.textfile}});if(t)throw".textfile error: "+t;if(!s){if(await F.yE(n))throw"file not exist: "+e.textfile;if(await F.t7(n))throw"file not readable: "+e.textfile}e.textfile=n}let n,s,r,o,i;if(e.getpcd.category_autocolor){const t=e.getpcd.values_count&&e.getpcd.values_count<=10?cr:gr;n=lr.Z(t),r={},o={}}else if(e.getpcd.category_customcolor){const t=lr.Z(gr);a=e.getpcd.cat_values,l=t,n=e=>{let t=!1;for(const n of a)if(n.value==e)return t=!0,n.color;if(!t)return l(e)},r={},o={},i={}}else if(e.getpcd.gene_expression){const n=e.getpcd.gene_expression;if(!n.file)throw"gene_expression.file missing";{const[e,t,s]=F.ZX({query:{file:n.file}});if(e)throw e;n.file=t}if(!Number.isInteger(n.barcodecolumnidx))throw"gene_expression.barcodecolumnidx missing";if(!n.chr)throw"gene_expression.chr missing";if(!n.start)throw"gene_expression.start missing";if(!n.stop)throw"gene_expression.stop missing";if(!n.genename)throw"gene_expression.genename missing";if(!n.autoscale)throw"gene_expression: unknown scaling method";if(!n.color_min)throw"gene_expression.color_min missing at autoscale";if(!n.color_max)throw"gene_expression.color_max missing at autoscale";const r=(n.nochr?n.chr.replace("chr",""):n.chr)+":"+n.start+"-"+n.stop,o=new Map;s=new Map;let i=0,a=0;if(t.numbercellwithgeneexp=0,t.numbercelltotal=0,await F.UE({args:[n.file,r],callback:e=>{const s=JSON.parse(e.split("\t")[3]);s.gene==n.genename&&Number.isFinite(s.value)&&(t.numbercellwithgeneexp++,n.autoscale&&(i=Math.min(i,s.value),a=Math.max(a,s.value)),o.set(s.sample,s.value))}}),n.autoscale){t.minexpvalue=i,t.maxexpvalue=a;const e=Pe.ZP(n.color_min,n.color_max);for(const[t,n]of o){const r=ke.ZP(e((n-i)/(a-i)));s.set(t,Number.parseInt(br(r.r,r.g,r.b),16))}}}var a,l;return new Promise(((i,a)=>{const l=[],c=I().createInterface({input:h().createReadStream(e.textfile)});let f=!0,u=0,d=0;c.on("line",(i=>{if(f)return void(f=!1);const a=i.split(e.delimiter),c=[];for(const t of e.getpcd.coord)c.push(a[t]),u=Math.max(u,a[t]),d=Math.min(d,a[t]);if(2==e.getpcd.coord.length&&c.push("0"),n){const t=a[e.getpcd.category_index],s=n(t);if(e.hidden_types.includes(t))if(e.background_color){const t=ke.ZP(e.background_color),n=Number.parseInt(br(t.r,t.g,t.b),16);c.push(n)}else c.push(16777215);else c.push(Number.parseInt(s.slice(1),16));r&&(r[t]=s),o&&(o[t]=t in o?o[t]+1:1)}else if(s){t.numbercelltotal++;const n=a[e.getpcd.gene_expression.barcodecolumnidx];let r=s.get(n);if(void 0===r)if(e.getpcd.gene_expression.color_no_exp){const t=ke.ZP(e.getpcd.gene_expression.color_no_exp);r=Number.parseInt(br(t.r,t.g,t.b),16)}else r="2894892";c.push(r)}l.push(c.join(" "))})),c.on("close",(()=>{r&&(e.getpcd.category_customorder&&(r=function(e,t){let n={};const s=Object.keys(e).length;for(var r=1;r<=s;r++){const s=t.find((e=>{if(e.order==r)return e.value}));s&&(n[s.value]=e[s.value])}for(const s of t)s.order||(n[s.value]=e[s.value]);for(const s in e){t.find((e=>{if(e.value==JSON.stringify(s))return!0}))||(n[s]=e[s])}return n}(r,e.getpcd.cat_values)),t.category2color=r,t.categorycount=o),t.data_sphere_r=Math.max(Math.abs(u),Math.abs(d)),i(l)}))}))}(e,n),r="# .PCD v.7 - Point Cloud Data file format\nVERSION .7\nFIELDS x y z rgb\nSIZE 4 4 4 4\nTYPE F F F F\nCOUNT 1 1 1 1\nWIDTH 1200\nHEIGHT 800\nVIEWPOINT 0 0 0 1 0 0 0\nPOINTS 960000\nDATA ascii\n";n.pcddata=r+s.join("\n"),t.send(n)}(s,n);if(s.getgeneboxplot)return void await async function(e,t,n){const s=e.getgeneboxplot,r=e.getgeneboxplot.values_count&&e.getgeneboxplot.values_count<=10?lr.Z(cr):lr.Z(gr);if(!s.expfile)throw"getgeneboxplot.expfile missing";{const[e,t,n]=F.ZX({query:{file:s.expfile}});if(e)throw"getgeneboxplot.expfile error: "+e;s.expfile=t}if(!s.chr)throw"getgeneboxplot.chr missing";if(!s.start)throw"getgeneboxplot.start missing";if(!s.stop)throw"getgeneboxplot.stop missing";if(!s.genename)throw"getgeneboxplot.genename missing";const o=await vr(s),i=(s.nochr?s.chr.replace("chr",""):s.chr)+":"+s.start+"-"+s.stop;let a=0,l=0;await F.UE({args:[s.expfile,i],callback:e=>{const t=JSON.parse(e.split("\t")[3]);if(t.gene!=s.genename)return;if(!t.sample)return;if(!Number.isFinite(t.value))return;const n=o.get(t.sample);n&&(n.expvalue=t.value,a=Math.min(a,t.value),l=Math.max(l,t.value))}});const c=new Map;for(const[e,t]of o)c.has(t.category)||c.set(t.category,[]),s.exclude_cells&&0==parseInt(t.expvalue)||c.get(t.category).push({value:t.expvalue});const f=[],u=(d=rs.Z().domain([a,l]).ticks(20),e=>{const t=[];for(let e=1;e<d.length;e++)t.push(0);for(const n of e)for(let e=1;e<d.length;e++)if(n.value<=d[e]){t[e-1]++;break}return t});var d;for(const[e,t]of c){t.sort(((e,t)=>e.value-t.value));const n=F.JC(t);delete n.out;const s=r(e);n.category=e,n.color=s,n.numberofcells=t.length,n.density=u(t),f.push(n)}let p=[];if(e.getgeneboxplot.cat_values){const t=Object.keys(e.getgeneboxplot.cat_values).length;for(var m=1;m<=t;m++){const t=e.getgeneboxplot.cat_values.find((e=>{if(e.order==m)return e.value}));t&&p.push(f.filter((e=>e.category==t.value))[0])}for(const t of e.getgeneboxplot.cat_values)t.order||p.push(f.filter((e=>e.category==t.value))[0]);for(const t of f){e.getgeneboxplot.cat_values.find((e=>{if(e.value==t.category)return!0}))||p.push(t)}for(const t of p){const n=e.getgeneboxplot.cat_values.find((e=>{if(e.value==t.category)return e}));n&&n.color&&(t.color=n.color)}}else p=f;n.send({boxplots:p,minexpvalue:a,maxexpvalue:l})}(s,0,n);if(s.getheatmap)return void await async function(e,t,n){const s=e.getheatmap,r=[];if(!s.expfile)throw"getgeneboxplot.expfile missing";{const[e,t,n]=F.ZX({query:{file:s.expfile}});if(e)throw"getgeneboxplot.expfile error: "+e;s.expfile=t}s.gene_list.forEach((e=>{if(!e.chr)throw"getgeneboxplot.chr missing";if(!e.start)throw"getgeneboxplot.start missing";if(!e.stop)throw"getgeneboxplot.stop missing";if(!e.gene)throw"getgeneboxplot.genename missing"}));const o=await vr(s);for(const e of s.gene_list){const t=(e.nochr?e.chr.replace("chr",""):e.chr)+":"+e.start+"-"+e.stop;let n=0,i=0;const a=e.gene;await F.UE({args:[s.expfile,t],callback:t=>{const s=JSON.parse(t.split("\t")[3]);if(s.gene.toUpperCase()!==e.gene.toUpperCase())return;if(!s.sample)return;if(!Number.isFinite(s.value))return;const r=o.get(s.sample);r&&(r.expvalue=s.value,n=Math.min(n,s.value),i=Math.max(i,s.value))}});const l=new Map;for(const[e,t]of o)l.has(t.category)||l.set(t.category,[]),l.get(t.category).push({value:t.expvalue});const c=[];for(const[e,t]of l){let n=0;for(const e of t)n+=e.value;const s=t.length,r=(n/s).toFixed(3);c.push({category:e,mean:r,numberofcells:s})}r.push({genename:a,heatmap:c})}n.send({gene_heatmap:r})}(s,0,n)}catch(e){n.send({error:e.message||e}),e.stack&&console.log(e.stack)}}}(Pr)),Jr.post(Hr+"/massSession",(async function(e,t){try{const n=e.body.__sessionFor__,{filename:s,route:o,dslabel:i,embedder:a}=n||{};let l;if(s){const t={headers:e.headers,query:n};if(l=mr.i.getPayloadFromHeaderAuth(t,o),!l.email)throw"invalid credentials: no jwt.email";if(l.dslabel!=i||l.route!=o||l.embedder!=a)throw"invalid credentials: mismatched payload";delete e.body.__sessionFor__}const c=s||function(){const e=[];for(;e.length<15;){const t=46+Math.floor(80*Math.random());(t>=48&&t<=57||t>=65&&t<=90||t>=97&&t<=122)&&e.push(String.fromCharCode(t))}return e.join("")}(),f=JSON.stringify(e.body),u=s?hr(n,l):r().cachedir_massSession;await h().promises.access(u).then((()=>!0)).catch((()=>!1))||h().mkdirSync(u,{recursive:!0}),await F.Sf(y().join(u,c),f),t.send({id:c})}catch(e){t.send({error:e.message||e})}})),Jr.get(Hr+"/massSession",(async function(e,t){try{const n=e.query.id;if(!n)throw"session id missing";const{route:s,dslabel:o,embedder:i}=e.query,a=e.query.route?mr.i.getPayloadFromHeaderAuth(e,e.query.route):null,l=e.query.route?hr(e.query,a):r().cachedir_massSession,c=y().join(l,n);let f;try{f=(await h().promises.stat(c)).birthtime}catch(e){throw"invalid session"}const u=await F.b5(c),d=JSON.parse(u);if(e.query.route)return void t.send({state:d});const p=new Date,m=new Date(f),g=r().features.massSessionDuration||30,b=g-Math.round((p.getTime()-m.getTime())/864e5);t.send({state:d,sessionDaysLeft:b,massSessionDuration:g})}catch(e){t.send({error:e.message||e})}})),Jr.delete(Hr+"/massSession",(async function(e,t){try{const n=e.query.ids;if(!n)throw"session ids[] missing";const{route:s,dslabel:o,embedder:i}=e.query,a=e.query.route?mr.i.getPayloadFromHeaderAuth(e,e.query.route):null;if(!a)throw"missing credentials";const l=e.query.route?hr(e.query,a):r().cachedir_massSession,c=[];for(const e of n){const t=y().join(l,e);h().unlink(t,(e=>{if(e)throw c.push(e),e}))}c.length||t.send({status:"ok"})}catch(e){t.send({error:e.message||e})}})),Jr.get(Hr+"/sessionIds",(async function(e,t){try{const{filename:n,route:s,dslabel:r,embedder:o}=e.query,i=mr.i.getPayloadFromHeaderAuth(e,s);if(!i.email)throw"invalid credentials: no jwt.email";if(i.dslabel!=r||i.route!=s||i.embedder!=o)throw"invalid credentials: mismatched payload";const a=hr(e.query,i);if(!await h().promises.access(a).then((()=>!0)).catch((()=>!1)))return void t.send({status:"ok",sessionIds:[]});const l=await h().promises.readdir(a);t.send({status:"ok",sessionIds:l})}catch(e){t.status(401),t.send({error:e.message||e})}})),Jr.get(Hr+"/isoformbycoord",(async function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"invalid genome";if(!e.query.chr)throw"chr missing";const s=Number(e.query.pos);if(!Number.isInteger(s))throw"pos must be positive integer";const o=n.tracks.find((e=>e.__isgene));o||reject("no gene track");const i=[];await F.UE({args:[y().join(r().tpmasterdir,o.file),e.query.chr+":"+s+"-"+s],callback:e=>{const t=e.split("\t")[3];if(!t)return;const s=JSON.parse(t);if(!s.isoform)return;const r={isoform:s.isoform},o=n.genedb.getjsonbyisoform.get(s.isoform);o&&(r.name=JSON.parse(o.genemodel).name,r.isdefault=o.isdefault),i.push(r)}}),t.send({lst:i})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/ase",(async function(e,t){const n=e.query,s=3e6,o=5e5;try{const e=Pr[n.genome];if(!e)throw"invalid genome";if(!n.samplename)throw"samplename missing";if(!n.chr)throw"no chr";if(!n.start||!n.stop)throw"no start/stop";if(!n.rnabarheight)throw"no rnabarheight";if(!n.dnabarheight)throw"no dnabarheight";if(!Number.isInteger(n.barypad))throw"invalid barypad";if(n.rnamax&&!Number.isFinite(n.rnamax))throw"invalid value for rnamax";if(!n.checkrnabam)throw".checkrnabam{} missing";const i=uo(n.checkrnabam);if(i)throw i;if(n.refcolor||(n.refcolor="blue"),n.altcolor||(n.altcolor="red"),!e.tracks)throw"genome.tracks[] missing";const a=e.tracks.find((e=>e.__isgene));if(!a)throw"no gene track from this genome";await async function(e,t){if(e.rnabamfile)e.rnabamfile=y().join(r().tpmasterdir,e.rnabamfile);else{if(!e.rnabamurl)throw"no file or url for rna bam";e.rnabamurl_dir=await F.d1(e.rnabamurl,e.rnabamindexURL||e.rnabamurl+".bai")}if(e.rnabam_nochr=await F.Dp(e.rnabamfile||e.rnabamurl,t,e.rnabamurl_dir),e.vcffile)e.vcffile=y().join(r().tpmasterdir,e.vcffile);else{if(!e.vcfurl)throw"no file or url for vcf";e.vcfurl_dir=await F.d1(e.vcfurl,e.vcfindexURL)}e.vcf_nochr=await F.Jy(e.vcffile||e.vcfurl,e.vcfurl_dir,t)}(n,e);const l=await go(e,a,n.chr,n.start,n.stop),c={};if(n.stop-n.start<s)for(const[e,t]of l){const e={file:n.rnabamfile,url:n.rnabamurl,dir:n.rnabamurl_dir,nochr:n.rnabam_nochr};let s;s=n.rnabamispairedend?await io(e,n.chr,t):await oo(e,n.chr,t),t.fpkm=1e9*s/(n.rnabamtotalreads*t.exonlength)}else c.fpkmrangelimit=s;const[f,u,d,p]=function(e,t){let n=e.start,s=e.stop;for(const[e,r]of t)n=Math.min(n,r.start),s=Math.max(s,r.stop);const r=e.start,o=e.stop;return[n,s,r,o]}(n,l),m=await async function(e,t,n,s,r){const o=await bo(e.vcffile||e.vcfurl,e.vcfurl_dir),[i,a,l,c]=D.e(o);if(c)throw c;const f={info:i,format:a,samples:l},u=await yo(e.vcffile||e.vcfurl,(e.vcf_nochr?e.chr.replace("chr",""):e.chr)+":"+s+"-"+r,e.vcfurl_dir),d=[];for(const t of u||[]){const[n,s,r]=D.S(t,f);for(const t of s){if(!$.basecolor[t.ref]||!$.basecolor[t.alt])continue;if(!t.sampledata)continue;const n=ho(t,e.samplename,e.checkrnabam);n&&d.push(n)}}const p=[];for(const e of d)for(const[t,s]of n)if(e.pos>=s.start&&e.pos<=s.stop){p.push(e);break}return p}(n,0,l,f,u);for(const e of m)e.rnacount={nocoverage:1};let g,b;p-d>=o?c.covplotrangelimit=o:(n.rnamax?g=n.rnamax:(g=await async function(e,t,n){let s=0;return await F.UE({isbam:!0,args:["depth","-r",(e.rnabam_nochr?e.chr.replace("chr",""):e.chr)+":"+(t+1)+"-"+(n+1),"-g","DUP",e.rnabamurl||e.rnabamfile],dir:e.rnabamurl_dir,callback:e=>{const t=e.split("\t");if(3!=t.length)return;const n=Number.parseInt(t[2]);Number.isInteger(n)&&(s=Math.max(s,n))}}),s}(n,d,p),c.rnamax=g),b=await async function(e,t,n,s,r){const o=new Map;for(const e of s)e.dnacount.ishet&&e.pos>=t&&e.pos<=n&&o.set(e.pos,e);const i=(0,S.createCanvas)(e.width*e.devicePixelRatio,(e.rnabarheight+e.barypad+e.dnabarheight)*e.devicePixelRatio),a=i.getContext("2d");e.devicePixelRatio>1&&a.scale(e.devicePixelRatio,e.devicePixelRatio);let l,c,f=!1;n-t<=e.width?(f=!0,l=1,c=e.width/(n-t),a.lineWidth=c):(c=1,l=(n-t)/e.width);return await F.UE({isbam:!0,args:["depth","-r",(e.rnabam_nochr?e.chr.replace("chr",""):e.chr)+":"+(t+1)+"-"+(n+1),"-g","DUP",e.rnabamurl||e.rnabamfile],dir:e.rnabamurl_dir,callback:n=>{const s=n.split("\t");if(3!=s.length)return;const i=Number.parseInt(s[1])-1;if(!Number.isInteger(i))return;const u=Number.parseInt(s[2]);if(!Number.isInteger(u))return;const d=e.rnabarheight*Math.min(u,r)/r,p=f?(i-t)*c:(i-t)/l;a.strokeStyle="#ccc",a.beginPath(),a.moveTo(p+c/2,e.rnabarheight),a.lineTo(p+c/2,e.rnabarheight-d),a.stroke(),a.closePath(),u>r&&(a.strokeStyle="blue",a.beginPath(),a.moveTo(p+c/2,0),a.lineTo(p+c/2,2),a.stroke(),a.closePath());const m=o.get(i);m&&(m.rnacount.h=d)}}),{canvas:i,ctx:a,isbp:f,binpxw:c,binbpsize:l}}(n,d,p,m,g)),c.coveragesrc=await function(e,t,n,s,r,o,i,a){const l=[];for(const n of t)n.dnacount.ishet&&l.push((e.rnabam_nochr?e.chr.replace("chr",""):e.chr)+":"+(n.pos+1)+"-"+(n.pos+1));return new Promise(((n,s)=>{const c=(0,x.spawn)(Br,["mpileup","-q",e.checkrnabam.rnapileup_q,"-Q",e.checkrnabam.rnapileup_Q,"--no-reference","-a","INFO/AD","-d",999999,"-r",l.join(","),e.rnabamurl||e.rnabamfile],{cwd:e.rnabamurl_dir});I().createInterface({input:c.stdout}).on("line",(e=>{if("#"==e[0])return;const n=mo(e);if(!n)return;let s;n.pos>=r&&n.pos<=o&&n.DP;const i=t.find((e=>e.pos==n.pos));if(i){i.__x=s;const e=n.allele2count[i.ref]||0,t=n.allele2count[i.alt]||0;e+t>0&&(delete i.rnacount.nocoverage,i.rnacount.ref=e,i.rnacount.alt=t,i.rnacount.f=t/(e+t))}})),c.on("close",(()=>{if(!i)return void n();const{canvas:s,ctx:l,binpxw:c}=i;l.lineWidth=Math.max(3,c);let f=0;for(const n of t)n.dnacount&&(n.pos<r||n.pos>o||(n.__x=e.width*(n.pos-r)/(o-r),f=Math.max(f,n.dnacount.ref+n.dnacount.alt)));for(const n of t){if(null==n.__x)continue;n.rnacount.nocoverage||(null==n.rnacount.h&&(n.rnacount.h=e.rnabarheight*(n.rnacount.ref+n.rnacount.alt)/a),l.strokeStyle=e.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,e.rnabarheight),l.lineTo(n.__x+c/2,e.rnabarheight-(1-n.rnacount.f)*n.rnacount.h),l.stroke(),l.closePath(),l.strokeStyle=e.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,e.rnabarheight-(1-n.rnacount.f)*n.rnacount.h),l.lineTo(n.__x+c/2,e.rnabarheight-n.rnacount.h),l.stroke(),l.closePath());const t=e.dnabarheight*(n.dnacount.ref+n.dnacount.alt)/f;n.dnacount.ishet&&(l.strokeStyle=e.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,e.rnabarheight+e.barypad),l.lineTo(n.__x+c/2,e.rnabarheight+e.barypad+(1-n.dnacount.f)*t),l.stroke(),l.closePath(),l.strokeStyle=e.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,e.rnabarheight+e.barypad+(1-n.dnacount.f)*t),l.lineTo(n.__x+c/2,e.rnabarheight+e.barypad+t),l.stroke(),l.closePath()),delete n.__x}n(s.toDataURL())}))}))}(n,m,0,0,d,p,b,g),await async function(e,t){if(0==e.length)return;const n=[];for(const s of e)s.rnacount.nocoverage||s.rnacount.ref+s.rnacount.alt<t.checkrnabam.rna_mintotalreads||n.push(s);if(0==n.length)return;const s=await function(e){const t=y().join(r().cachedir,Math.random().toString())+".snp",n=[];for(const t of e)t.rnacount.nocoverage||null!=t.rnacount.ref&&null!=t.rnacount.alt&&n.push(t.pos+"."+t.ref+"."+t.alt+"\t\t\t\t\t\t\t\t"+t.rnacount.ref+"\t"+t.rnacount.alt);return new Promise(((e,s)=>{h().writeFile(t,n.join("\n")+"\n",(n=>{n&&s("cannot write"),e(t)}))}))}(n),o=await po(s);await function(e,t){return new Promise(((n,s)=>{h().readFile(t,"utf8",((t,r)=>{t&&s("cannot read binom pvalue"),r||n();for(const t of r.trim().split("\n")){const n=t.split("\t"),s=e.find((e=>n[0]==e.pos+"."+e.ref+"."+e.alt));s&&(s.rnacount.pvalue=Number.parseFloat(n[10]))}n()}))}))}(e,o),h().unlink(s,(()=>{})),h().unlink(o,(()=>{}))}(m,n),c.genes=function(e,t,n){const s=[];for(const[r,o]of t){s.push(o);const t=e.filter((e=>e.pos>=o.start&&e.pos<=o.stop));if(0==t.length){o.nosnp=1;continue}o.snps=t;const r=t.filter((e=>null!=e.rnacount.pvalue));if(0==r.length){o.nornasnp=1;continue}const i=r.reduce(((e,t)=>e+Math.abs(t.rnacount.f-.5)),0);let a=null,l=0;for(const e of r)null==a?a=e.rnacount.pvalue:a*=e.rnacount.pvalue,e.rnacount.pvalue<=n.checkrnabam.binompvaluecutoff&&l++;o.ase={markers:t.filter((e=>e.dnacount.ishet)).length,ase_markers:l,mean_delta:i/r.length,geometricmean:Math.pow(a,1/r.length)}}return s}(m,l,n);let v=0;for(const e of m)e.dnacount&&e.pos>=d&&e.pos<=p&&(v=Math.max(v,e.dnacount.ref+e.dnacount.alt));c.dnamax=v,t.send(c)}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/bamnochr",(async function(e,t){const n=e.query;try{const e=Pr[n.genome];if(!e)throw"invalid genome";if(n.file)n.file=y().join(r().tpmasterdir,n.file);else{if(!n.url)throw"no bam file or url";n.url_dir=await F.d1(n.url,n.indexURL||n.url+".bai")}const s=await F.Dp(n.file||n.url,e,n.url_dir);t.send({nochr:s})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.get(Hr+"/gene2canonicalisoform",(function(e,t){try{if(!e.query.gene)throw".gene missing";const n=Pr[e.query.genome];if(!n)throw"unknown genome";if(!n.genedb.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const s=n.genedb.get_gene2canonicalisoform.get(e.query.gene);t.send(s)}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Jr.get(Hr+"/ideogram",(function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"invalid genome";if(!n.genedb.hasIdeogram)throw"ideogram not supported on this genome";if(!e.query.chr)throw".chr missing";const s=n.genedb.getIdeogramByChr.all(e.query.chr);if(!s.length)throw"no ideogram data for this chr";t.send(s)}catch(e){t.send({error:e.message||e})}}));F.lY,F.ZX;function To(e){const t=e.split(/\r?\n/);if(t.length<=1||!t[0])return[null,[]];const n=t[0].split("\t"),s=[];for(let e=1;e<t.length;e++){if("#"==t[e][0])continue;const r=t[e].split("\t"),o={};for(let e=0;e<n.length;e++){const t=r[e];t&&(o[n[e]]=t)}s.push(o)}return[null,s]}async function Mo(e){try{await h().promises.stat(e.tpmasterdir)}catch(t){const n="Error with "+e.tpmasterdir+": "+t.code;if("validate"==process.argv[2])throw n;return void console.log("\n!!! "+n+"\n")}if(function(){if(r().features.skip_checkDependenciesAndVersions)return void console.log("SKIPPED checkDependenciesAndVersions()");const e=["jsonlite","cmprsk","hwde","lmtest"];for(const t of e){const e=N().spawnSync(r().Rscript,["-e",`suppressPackageStartupMessages(library("${t}"))`],{encoding:"utf8"});if(e.stderr.trim())throw e.stderr}const t=10;{const e=N().execSync(r().samtools+" --version",{encoding:"utf8"}).trim().split("\n"),[n,s]=e[0].split(" ");if("samtools"!=n||!s)throw'cannot run "samtools version"';const[o,i]=s.split(".");if("1"!=o)throw"samtools not 1.*";if(Number(i)<t)throw`samtools not >= 1.${t}`}{const e=N().execSync(r().bcftools+" -v",{encoding:"utf8"}).trim().split("\n"),[n,s]=e[0].split(" ");if("bcftools"!=n||!s)throw'cannot run "bcftools version"';const[o,i]=s.split(".");if("1"!=o)throw"bcftools not 1.*";if(Number(i)<t)throw`bcftools not >= 1.${t}`}}(),null!=e.base_zindex){const t=Number.parseInt(e.base_zindex);if(Number.isNaN(t)||t<=0)throw"base_zindex must be positive integer";e.base_zindex=t}if(e.jwt){if(!e.jwt.secret)throw"jwt.secret missing";if(!e.jwt.permissioncheck)throw"jwt.permissioncheck missing"}if(!e.tpmasterdir)throw".tpmasterdir missing";if(!e.cachedir)throw".cachedir missing";if(e.cachedir_massSession=await Eo("massSession"),e.cachedir_massSessionTrash=await Eo("massSessionTrash"),e.cache_snpgt={dir:await Eo("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},e.cachedir_bam=await Eo("bam"),e.cachedir_genome=await Eo("genome"),e.cachedir_ssid=await Eo("ssid"),e.commonOverrides&&$.applyOverrides(e.commonOverrides),!e.genomes)throw".genomes[] missing";if(!Array.isArray(e.genomes))throw".genomes[] not array";for(const t of e.genomes){if(!t.name)throw".name missing from a genome: "+JSON.stringify(t);if(!t.file)throw".file missing from genome "+t.name;const n=y().join(process.cwd(),t.file),s=require(h().existsSync(n)?n:t.file),r=s.default||s;if(Pr[t.name]=r,!r.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==r.genomefile||(r.genomefile=y().join(e.tpmasterdir,r.genomefile)),r.genomicNameRegexp||(r.genomicNameRegexp=/[^a-zA-Z0-9.:_-]/),r.tracks||(r.tracks=[]),t.tracks)for(const e of t.tracks)r.tracks.push(e);if(t.datasets&&(r.rawdslst=t.datasets),t.snp&&(r.snp=t.snp),t.blat){if(!t.blat.host)throw".blat.host missing for "+t.name;if(!t.blat.port)throw".blat.port missing for "+t.name;r.blat=t.blat}if(t.nosnp&&delete r.snp,t.nohicenzyme&&delete r.hicenzymefragment,t.nohicdomain&&delete r.hicdomain,r.genedb&&t.no_gene2canonicalisoform&&delete r.genedb.gene2canonicalisoform,t.updateAttr)for(const e of t.updateAttr){let t=r;for(const[n,s]of e.entries())if(t)if("object"==typeof s)for(const e in s)t[e]=s[e];else{if("string"==typeof t[s]){e[n+1]&&(t[s]=e[n+1]);break}t=t[s]}}}e.defaultgenome&&Pr[e.defaultgenome]&&(Pr[e.defaultgenome].isdefault=!0);for(const t in Pr){const n=Pr[t];if(!n.majorchr)throw t+": majorchr missing";if(!n.defaultcoord)throw t+": defaultcoord missing";if(await F.Kf(n,n.defaultcoord.chr+":"+n.defaultcoord.start+"-"+(n.defaultcoord.start+1)),n.tracks||(n.tracks=[]),"string"==typeof n.majorchr){const e=n.majorchr.trim().split(/[\s\t\n]+/),s={},r=[];for(let n=0;n<e.length;n+=2){const o=e[n],i=Number.parseInt(e[n+1]);if(Number.isNaN(i))throw t+" majorchr invalid chr size for "+o+" ("+e[n+1]+")";s[o]=i,r.push(o)}n.majorchr=s,n.majorchrorder=r}n.chrlookup={};for(const e in n.majorchr)n.chrlookup[e.toUpperCase()]={name:e,len:n.majorchr[e],major:!0};if(n.minorchr){if("string"==typeof n.minorchr){const e=n.minorchr.trim().split(/[\s\t\n]+/),s={};for(let n=0;n<e.length;n+=2){const r=Number.parseInt(e[n+1]);if(Number.isNaN(r))throw t+" minorchr invalid chr size for "+e[n]+" ("+e[n+1]+")";s[e[n]]=r}n.minorchr=s}for(const e in n.minorchr)n.chrlookup[e.toUpperCase()]={name:e,len:n.minorchr[e]}}if(n.genedb){if(!n.genedb.dbfile)throw t+": .genedb.dbfile missing";try{console.log("Connecting",n.genedb.dbfile),n.genedb.db=F.sE(n.genedb.dbfile)}catch(e){throw`Cannot connect genedb: ${n.genedb.dbfile}: ${e}`}n.genedb.getnamebynameorisoform=n.genedb.db.prepare("select name from genes where name=? or isoform=?"),n.genedb.getnamebyisoform=n.genedb.db.prepare("select distinct name from genes where isoform=?"),n.genedb.getjsonbyname=n.genedb.db.prepare("select isdefault,genemodel from genes where name=?"),n.genedb.getjsonbyisoform=n.genedb.db.prepare("select isdefault,genemodel from genes where isoform=?"),n.genedb.getnameslike=n.genedb.db.prepare("select distinct name from genes where name like ? limit 20");const e=(0,vs.jj)(n.genedb.db);e.has("genealias")&&(n.genedb.getNameByAlias=n.genedb.db.prepare("select name from genealias where alias=?"),n.genedb.getAliasByName=n.genedb.db.prepare("select alias from genealias where name=?")),e.has("gene2coord")&&(n.genedb.getCoordByGene=n.genedb.db.prepare("select * from gene2coord where name=?")),e.has("ideogram")?(n.genedb.hasIdeogram=!0,n.genedb.getIdeogramByChr=n.genedb.db.prepare("select * from ideogram where chromosome=?")):n.genedb.hasIdeogram=!1,e.has("gene2canonicalisoform")&&(n.genedb.get_gene2canonicalisoform=n.genedb.db.prepare("select isoform from gene2canonicalisoform where gene=?")),e.has("buildDate")&&(n.genedb.get_buildDate=n.genedb.db.prepare("select date from buildDate")),n.genedb.hasTable_refseq2ensembl=e.has("refseq2ensembl"),n.genedb.sqlTables=[...e],n.genedb.tableSize={};for(const t of e)"buildDate"!=t&&(n.genedb.tableSize[t]=n.genedb.db.prepare(`select count(*) as size from ${t}`).get().size)}if(n.termdbs)for(const e in n.termdbs)(0,vs.JV)(n.termdbs[e],Lr),console.log(`${e} initiated as ${t}-level termdb`);for(const t of n.tracks)if(t.__isgene){if(!t.file)throw"Tabix file missing for gene track: "+JSON.stringify(t);try{await F.LC(y().join(e.tpmasterdir,t.file))}catch(e){throw"Error with "+t.file+": "+e}}if(n.proteindomain){if(!n.proteindomain.dbfile)throw t+".proteindomain: missing dbfile for sqlite db";if(!n.proteindomain.statement)throw t+".proteindomain: missing statement for sqlite db";let e;try{console.log("Connecting",n.proteindomain.dbfile),e=F.sE(n.proteindomain.dbfile)}catch(e){throw"Error with "+n.proteindomain.dbfile+": "+e}n.proteindomain.getbyisoform=e.prepare(n.proteindomain.statement)}if(n.snp){if(!n.snp.bigbedfile)throw t+".snp: missing bigBed file";n.snp.bigbedfile=y().join(e.tpmasterdir,n.snp.bigbedfile),await F.Ic(n.snp.bigbedfile)}if(n.fimo_motif){if(!n.fimo_motif.db)throw t+".fimo_motif: db file missing";if(n.fimo_motif.db=y().join(e.tpmasterdir,n.fimo_motif.db),n.fimo_motif.annotationfile){const[t,s]=To(h().readFileSync(y().join(e.tpmasterdir,n.fimo_motif.annotationfile),{encoding:"utf8"}).trim());n.fimo_motif.tf2attr={};for(const e of s)n.fimo_motif.tf2attr[e.Model.split("_")[0]]=e}}if(n.hicenzymefragment){if(!Array.isArray(n.hicenzymefragment))throw"hicenzymefragment should be an array";for(const t of n.hicenzymefragment){if(!t.enzyme)throw".enzyme missing for one element of hicenzymefragment[]";if(!t.file)throw".file missing for one element of hicenzymefragment[]";try{await F.LC(y().join(e.tpmasterdir,t.file))}catch(e){throw"Error with "+t.file+": "+e}}}if(n.hicdomain){if(!n.hicdomain.groups)throw".groups{} missing from hicdomain";for(const t in n.hicdomain.groups){const s=n.hicdomain.groups[t];if(!s.name)throw".name missing from hicdomain "+t;if(!s.sets)throw".set{} missing from hicdomain "+t;for(const n in s.sets){const r=s.sets[n];if(!r.name)throw".name missing from hicdomain "+t+" > "+n;if(!r.file)throw".file missing from hicdomain "+t+" > "+n;r.file=y().join(e.tpmasterdir,r.file);try{await F.LC(r.file)}catch(e){throw"Error with "+r.file+": "+e}}}}if(n.rawdslst){n.datasets={};for(const e of n.rawdslst){if(e.skip)continue;if(!e.name)throw"a nameless dataset from "+t;if(n.datasets[e.name])throw t+" has duplicating dataset name: "+e.name;if(!e.jsfile)throw"jsfile not available for dataset "+e.name+" of "+t;const s=y().join(process.cwd(),e.jsfile),r=require(h().existsSync(s)?s:e.jsfile),o="function"==typeof r?r($):"function"==typeof r?.default?r.default($):r.default||r;if(ws(o,e),o.noHandleOnClient=e.noHandleOnClient,o.label=e.name,o.genomename=t,n.datasets[o.label]=o,o.isMds3)try{await Ms(o,n,0,Jr,Hr)}catch(e){throw e.stack&&console.log(e.stack),"Error with mds3 dataset "+o.label+": "+e}else if(o.isMds)try{await Fo(o,n,e)}catch(e){throw"Error with mds dataset "+o.label+": "+e}else Io(o,n)}Oo(),delete n.rawdslst}}}async function Oo(){const e=await h().promises.readdir(r().cachedir_massSession);try{e.forEach((async e=>{const t=(await h().promises.stat(y().join(r().cachedir_massSession,e))).birthtime,n=new Date,s=new Date(t),o=r().features.massSessionDuration||30;Math.round((n.getTime()-s.getTime())/864e5)>o&&(await h().promises.copyFile(y().join(r().cachedir_massSession,e),y().join(r().cachedir_massSessionTrash,e)),await h().promises.unlink(y().join(r().cachedir_massSession,e)),console.log("File deleted: ",e,t))}))}catch(e){throw`Error: ${e}`}}function Io(e,t){if(e.dbfile)try{console.log("Connecting",e.dbfile),e.newconn=F.sE(e.dbfile)}catch(t){throw"Error with "+e.dbfile+": "+t}if(e.snvindel_attributes)for(const t of e.snvindel_attributes)if(t.lst)for(const e of t.lst)e.get=e.get.toString();else t.get=t.get.toString();if(e.cohort){if(e.cohort.levels){if(!Array.isArray(e.cohort.levels))throw"cohort.levels must be array for "+e.genomename+"."+e.label;if(0==e.cohort.levels.length)throw"levels is blank array for cohort of "+e.genomename+"."+e.label;for(const t of e.cohort.levels)if(!t.k)throw".k key missing in one of the levels, .cohort, in "+e.genomename+"."+e.label}if(e.cohort.fromdb){if(!e.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+e.genomename+"."+e.label;const t=e.newconn.prepare(e.cohort.fromdb.sql).all();delete e.cohort.fromdb,e.cohort.raw=t,console.log(t.length+" rows retrieved for "+e.label+" sample annotation")}if(e.cohort.files){let t=[];for(const n of e.cohort.files){if(!n.file)throw".file missing from one of cohort.files[] for "+e.genomename+"."+e.label;const s=h().readFileSync(y().join(r().tpmasterdir,n.file),"utf8").trim();if(!s)throw n.file+" is empty for "+e.genomename+"."+e.label;t=[...t,...ee(s)]}delete e.cohort.files,e.cohort.raw?e.cohort.raw=[...e.cohort.raw,...t]:e.cohort.raw=t,console.log(t.length+" rows retrieved for "+e.label+" sample annotation")}if(e.cohort.tosampleannotation){if(!e.cohort.tosampleannotation.samplekey)throw".samplekey missing from .cohort.tosampleannotation for "+e.genomename+"."+e.label;if(!e.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+e.genomename+"."+e.label}}if(!e.queries)throw".queries missing from dataset "+e.label+", "+e.genomename;if(!Array.isArray(e.queries))throw e.label+".queries is not array";for(const n of e.queries){const s=Ro(n,e,t);if(s)throw'Error parsing a query in "'+e.label+'": '+s}if(e.vcfinfofilter){const t=$.validate_vcfinfofilter(e.vcfinfofilter);if(t)throw e.label+": vcfinfofilter error: "+t}if(e.url4variant)for(const t of e.url4variant){if(!t.makelabel)throw"makelabel() missing for one item of url4variant from "+e.label;if(!t.makeurl)throw"makeurl() missing for one item of url4variant from "+e.label;t.makelabel=t.makelabel.toString(),t.makeurl=t.makeurl.toString()}}async function Eo(e){const t=y().join(r().cachedir,e);try{await h().promises.stat(t)}catch(e){if("ENOENT"!=e.code)throw"error stating dir";try{await h().promises.mkdir(t)}catch(e){throw"cannot make dir"}}return t}function Ro(e,t,n){if(!e.name)return".name missing";if(e.dsblocktracklst){if(!Array.isArray(e.dsblocktracklst))return"dsblocktracklst not an array in "+t.label;for(const n of e.dsblocktracklst){if(!n.type)return"missing type for a blocktrack of "+t.label;if(!n.file&&!n.url)return"neither file or url given for a blocktrack of "+t.label}}else if(e.vcffile){const t=N().execSync(Gr+" -H "+y().join(r().tpmasterdir,e.vcffile),{encoding:"utf8"}).trim();if(""==t)return"no meta lines in VCF file "+e.vcffile+" of query "+e.name;const[s,o,i,a]=D.e(t.split("\n"));if(a)return"error parsing VCF meta lines of "+e.vcffile+": "+a.join("; ");e.vcf={vcfid:Math.random().toString(),info:s,format:o,samples:i},e.hlinfo&&(e.vcf.hlinfo=e.hlinfo,delete e.hlinfo),e.infopipejoin&&(e.vcf.infopipejoin=e.infopipejoin,delete e.infopipejoin);const l=N().execSync(Gr+" -l "+y().join(r().tpmasterdir,e.vcffile),{encoding:"utf8"}).trim();if(""==l)return"tabix -l found no chromosomes/contigs in "+e.vcffile+" of query "+e.name;e.vcf.nochr=$.contigNameNoChr(n,l.split("\n"));let c=0;if(s)for(const e in s)c++;console.log("Parsed vcf meta from "+e.vcffile+": "+c+" INFO, "+i.length+" sample, "+(e.vcf.nochr?'no "chr"':'has "chr"'))}else{if(!e.makequery)return"do not know how to parse query: "+e.name;if(e.isgeneexpression){if(!e.config)return"config object missing for gene expression query of "+e.name;e.config.maf&&(e.config.maf.get=e.config.maf.get.toString())}}}async function Fo(e,t,n){if((e.isMds2||e.isMds3||e.isMds)&&ws(e,n),e.assayAvailability){if(!e.assayAvailability.file)throw".assayAvailability.file missing";if(!e.assayAvailability.assays)throw".assayAvailability.assays[] missing";Object.freeze(e.assayAvailability.assays),e.assayAvailability.samples=new Map;for(const t of h().readFileSync(y().join(r().tpmasterdir,e.assayAvailability.file),{encoding:"utf8"}).trim().split("\n")){const[n,s]=t.split("\t");e.assayAvailability.samples.set(n,JSON.parse(s))}console.log(e.assayAvailability.samples.size+" samples with assay availability ("+e.label+")")}if(e.gene2mutcount){if(!e.gene2mutcount.dbfile)throw".gene2mutcount.dbfile missing";try{console.log("Connecting",e.gene2mutcount.dbfile),e.gene2mutcount.db=F.sE(e.gene2mutcount.dbfile),console.log("DB connected for "+e.label+": "+e.gene2mutcount.dbfile)}catch(t){throw`Error connecting db at ${e.gene2mutcount.dbfile}`}}if(e.sampleAssayTrack){if(!e.sampleAssayTrack.file)throw".file missing from sampleAssayTrack";e.sampleAssayTrack.samples=new Map;let t=0,n=new Set;for(const s of h().readFileSync(y().join(r().tpmasterdir,e.sampleAssayTrack.file),{encoding:"utf8"}).trim().split("\n")){if(!s)continue;if("#"==s[0])continue;const[r,o,i]=s.split("\t");if(!o||!i)continue;if(!e.sampleAssayTrack.samples.has(r)){if(e.cohort&&e.cohort.annotation&&!e.cohort.annotation[r]){n.add(r);continue}e.sampleAssayTrack.samples.set(r,[])}const a=JSON.parse(i);if(!$.tkt[a.type])throw"invalid type from a sample track: "+i;a.name||(a.name=r+" "+o),a.assayName=o,e.sampleAssayTrack.samples.get(r).push(a),t++}console.log(t+" assay-tracks from "+e.sampleAssayTrack.samples.size+" samples ("+e.label+")"),n.size&&console.log("Error: "+n.size+" samples with assay tracks are unannotated: "+[...n].join(" "))}if(e.singlesamplemutationjson){const t=e.singlesamplemutationjson;if(!t.file)throw".file missing from singlesamplemutationjson";t.samples={};let n=0;for(const e of h().readFileSync(y().join(r().tpmasterdir,t.file),{encoding:"utf8"}).trim().split("\n")){if(!e)continue;if("#"==e[0])continue;const[s,r]=e.split("\t");s&&r&&(n++,t.samples[s]=r)}console.log(n+" samples for disco plot")}if(e.cohort&&e.cohort.db&&e.cohort.termdb&&await Xs(e,Jr,Hr),e.cohort&&e.cohort.files){if(!Array.isArray(e.cohort.files))throw".cohort.files is not array";if(!e.cohort.tohash)throw".tohash() missing from cohort";if("function"!=typeof e.cohort.tohash)throw".cohort.tohash is not function";if(!e.cohort.samplenamekey)throw".samplenamekey missing";if(e.cohort.annotation={},e.cohort.mutation_signature){const t=e.cohort.mutation_signature;if(!t.sets)throw".mutation_signature.sets missing";for(const n in t.sets){const s=t.sets[n];if(s.name||(s.name=n),!s.signatures)throw".signatures{} missing from a signature set";if(s.samples){if(!s.samples.file)throw".samples.file missing from a signature set";const[t,n]=To(h().readFileSync(y().join(r().tpmasterdir,s.samples.file),{encoding:"utf8"}).trim());s.samples.map=new Map;for(const t of n){const n=t[e.cohort.samplenamekey];if(!n)throw e.cohort.samplenamekey+" missing in file "+s.samples.file;s.samples.map.set(n,t);for(const e in s.signatures)if(t[e]){const r=Number.parseFloat(t[e]);if(Number.isNaN(r))throw"mutation signature value is not float: "+t[e]+" from sample "+n;s.samples.skipzero&&0==r?delete t[e]:t[e]=r}}}}}if(e.cohort.attributes){if(!e.cohort.attributes.lst)throw".lst[] missing for cohort.attributes";if(!Array.isArray(e.cohort.attributes.lst))return".cohort.attributes.lst is not array";for(const t of e.cohort.attributes.lst){if(!t.key)throw".key missing from one of the .cohort.attributes.lst[]";if(!t.label)throw".label missing from one of the .cohort.attributes.lst[]";if(!t.values)throw".values{} missing from "+t.label+" of .cohort.attributes.lst";for(const e in t.values)if(!t.values[e].label)throw".label missing from one value of "+t.label+" in .cohort.attributes.lst"}if(e.cohort.attributes.defaulthidden)for(const t in e.cohort.attributes.defaulthidden){const n=e.cohort.attributes.lst.find((e=>e.key==t));if(!n)throw"invalid defaulthidden key: "+t;for(const s in e.cohort.attributes.defaulthidden[t])if(!n.values[s])throw"invalid defaulthidden value "+s+" for "+t}}if(e.cohort.hierarchies){if(!e.cohort.hierarchies.lst)throw".lst[] missing from .cohort.hierarchies";if(!Array.isArray(e.cohort.hierarchies.lst))throw".cohort.hierarchies.lst is not array";for(const t of e.cohort.hierarchies.lst){if(!t.name)throw".name missing from one hierarchy";if(!t.levels)throw".levels[] missing from one hierarchy";if(!Array.isArray(t.levels))throw".levels is not array from one hierarchy";for(const e of t.levels)if(!e.k)throw".k missing from one level in hierarchy "+t.name}}if(e.cohort.sampleAttribute){if(!e.cohort.sampleAttribute.attributes)throw"attributes{} missing from cohort.sampleAttribute";for(const t in e.cohort.sampleAttribute.attributes){const n=e.cohort.sampleAttribute.attributes[t];if(!n.label)throw".label missing for key "+t+" from cohort.sampleAttribute.attributes";if(n.values)for(const e in n.values){const t=n.values[e];if("object"!=typeof t)throw'value "'+e+'" not pointing to {} from sampleAttribute';t.name||(t.name=e)}if(n.showintrack&&!n.isinteger&&!n.isfloat)throw n.label+": .showintrack requires .isinteger or .isfloat"}}if(e.cohort.scatterplot){if(!e.cohort.sampleAttribute)throw".sampleAttribute missing but required for .cohort.scatterplot";const t=e.cohort.scatterplot;if(!t.querykey)throw".querykey missing from .cohort.scatterplot";{if(!e.queries)throw".cohort.scatterplot.querykey in use but ds.queries{} missing";const n=e.queries[t.querykey];if(!n)throw"unknown query by .cohort.scatterplot.querykey: "+t.querykey;if(n.type!=$.tkt.mdssvcnv)throw"type is not "+$.tkt.mdssvcnv+" of the track pointed to by .cohort.scatterplot.querykey"}if(t.colorbygeneexpression){if(!t.colorbygeneexpression.querykey)throw"querykey missing from .cohort.scatterplot.colorbygeneexpression";if(!e.queries)throw".cohort.scatterplot.colorbygeneexpression in use but ds.queries{} missing";const n=e.queries[t.colorbygeneexpression.querykey];if(!n)throw"unknown query by .cohort.scatterplot.colorbygeneexpression.querykey: "+t.colorbygeneexpression.querykey;if(!n.isgenenumeric)throw"isgenenumeric missing from the track pointed to by .cohort.scatterplot.colorbygeneexpression.querykey"}if(t.tracks,!t.x)throw".x missing from .cohort.scatterplot";if(!t.x.attribute)throw".attribute missing from .cohort.scatterplot.x";const n=e.cohort.sampleAttribute.attributes[t.x.attribute];if(!n)throw"scatterplot.x.attribute is not defined in sampleAttribute";if(!n.isfloat)throw'scatterplot.x is not "isfloat"';if(!t.y)throw".y missing from .cohort.scatterplot";if(!t.y.attribute)throw".attribute missing from .cohort.scatterplot.y";const s=e.cohort.sampleAttribute.attributes[t.y.attribute];if(!s)throw"scatterplot.y.attribute is not defined in sampleAttribute";if(!s.isfloat)throw'scatterplot.y is not "isfloat"';if(t.colorbyattributes)for(const n of t.colorbyattributes){if(!n.key)throw".key missing from one of scatterplot.colorbyattributes";const t=e.cohort.sampleAttribute.attributes[n.key];if(!t)throw"unknown attribute by key "+n.key+" from scatterplot.colorbyattributes";n.label=t.label,n.values=t.values}}for(const t of e.cohort.files){if(!t.file)throw".file missing from one of .cohort.files";const[n,s]=To(h().readFileSync(y().join(r().tpmasterdir,t.file),{encoding:"utf8"}).trim());if(n)throw'cohort annotation file "'+t.file+'": '+n;console.log(e.label+": "+s.length+" samples loaded from annotation file "+t.file),s.forEach((t=>{for(const n in t){let s;e.cohort.sampleAttribute&&(s=e.cohort.sampleAttribute.attributes[n]),s||e.cohort.termdb&&e.cohort.termdb.termjson&&e.cohort.termdb.termjson.map&&(s=e.cohort.termdb.termjson.map.get(n)),s&&(s.isfloat?t[n]=Number.parseFloat(t[n]):s.isinteger&&(t[n]=Number.parseInt(t[n])))}e.cohort.tohash(t,e)}))}if(e.cohort.annorows=Object.values(e.cohort.annotation),console.log(e.label+": total samples from sample table: "+e.cohort.annorows.length),e.cohort.survivalplot){const t=e.cohort.survivalplot;if(!t.plots)throw".plots{} missing from survivalplot";t.init={plottypes:[]};for(const e in t.plots){const n=t.plots[e];if(!n.name)throw".name missing from survivalplot "+e;if(!n.serialtimekey)throw".serialtimekey missing from survivalplot "+e;if(!n.iscensoredkey)throw".iscensoredkey missing from survivalplot "+e;if(!n.timelabel)throw".timelabel missing from survivalplot "+e;n.key=e,t.init.plottypes.push({key:e,name:n.name,timelabel:n.timelabel})}if(t.samplegroupattrlst){t.init.samplegroupings=[];for(const n of t.samplegroupattrlst){if(!n.key)throw".key missing from an attr of samplegroupattrlst for survival";const s=e.cohort.sampleAttribute.attributes[n.key];if(!s)throw'unknown attribute key "'+n.key+'" from survival samplegroupattrlst';const r=new Map;for(const s in e.cohort.annotation){const o=e.cohort.annotation[s],i=o[n.key];if(null==i)continue;let a=!1;for(const e in t.plots)if(null!=o[t.plots[e].serialtimekey]){a=!0;break}a&&(r.has(i)?r.set(i,r.get(i)+1):r.set(i,1))}if(0==r.size)throw'no value found for "'+n.key+'" from survival samplegroupattrlst';const o=[];for(const[e,t]of r)o.push({value:e,count:t});t.init.samplegroupings.push({key:n.key,label:s.label,values:o})}}}}if(e.mutationAttribute){if(!e.mutationAttribute.attributes)throw"attributes{} missing from mutationAttribute";for(const t in e.mutationAttribute.attributes){const n=e.mutationAttribute.attributes[t];if(!n.label)throw".label missing for key "+t+" from mutationAttribute.attributes";if(!n.appendto_link&&n.values)for(const e in n.values){if(!n.values[e].name)throw".name missing for value "+e+" of key "+t+" from mutationAttribute.attributes"}}}if(e.alleleAttribute){if(!e.alleleAttribute.attributes)throw"attributes{} missing from alleleAttribute";for(const t in e.alleleAttribute.attributes){const n=e.alleleAttribute.attributes[t];if(!n.label)throw".label missing for key "+t+" from alleleAttribute.attributes";if(!n.isnumeric){if(!n.values)throw".values{} missing for non-numeric key "+t+" from alleleAttribute.attributes";for(const e in n.values){if(!n.values[e].name)throw".name missing for value "+e+" of key "+t+" from alleleAttribute.attributes"}}}}if(e.locusAttribute){if(!e.locusAttribute.attributes)throw"attributes{} missing from locusAttribute";for(const t in e.locusAttribute.attributes){const n=e.locusAttribute.attributes[t];if(!n.label)throw".label missing for key "+t+" from locusAttribute.attributes";if(!n.isnumeric&&!n.appendto_link){if(!n.values)throw".values{} missing for non-numeric key "+t+" from locusAttribute.attributes";for(const e in n.values){if(!n.values[e].name)throw".name missing for value "+e+" of key "+t+" from locusAttribute.attributes"}}}}if(e.queries)for(const s in e.queries){if(n.remove_queries&&-1!=n.remove_queries.indexOf(s)){delete e.queries[s];continue}const r=e.queries[s];if(n.hide_queries&&-1!=n.hide_queries.indexOf(s)&&(r.hideforthemoment=1),r.istrack){if(!r.type)throw".type missing for track query "+s;if(r.viewrangeupperlimit&&!Number.isInteger(r.viewrangeupperlimit))throw".viewrangeupperlimit should be integer for track query 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missing in annotationsampleset2matrix";if("object"!=typeof e.annotationsampleset2matrix.groups)throw"ds.annotationsampleset2matrix.groups{} not an object";for(const t in e.annotationsampleset2matrix.groups){const n=e.annotationsampleset2matrix.groups[t];if(!n.groups||!Array.isArray(n.groups)||0==n.groups.length)throw".groups[] must be nonempty array in "+t;for(const s of n.groups){if(!s.name)throw".name missing from one of .groups[] in "+t;const n=s.matrixconfig;if(!n)throw".matrixconfig missing from one of .groups[] of "+t;if(!n.features)throw".features[] missing from group "+t;if(!Array.isArray(n.features))throw".features[] should be array from group "+t;if(0==n.features.length)throw".features[] zero length from group "+t;for(const s of n.features){if(e.annotationsampleset2matrix.commonfeatureattributes)for(const t in e.annotationsampleset2matrix.commonfeatureattributes)null==s[t]&&(s[t]=e.annotationsampleset2matrix.commonfeatureattributes[t]);if(!s.ismutation)return"unknown feature type from group "+t;if(!s.position)throw"position missing from feature "+JSON.stringify(s)+" from group "+t;if(!s.querykeylst)throw".querykeylst[] missing from ismutation feature from group "+t;if(!Array.isArray(s.querykeylst))throw".querykeylst[] not an array from ismutation feature from group "+t;if(0==s.querykeylst.length)throw".querykeylst[] zero length from ismutation feature from group "+t;for(const n of s.querykeylst)if(!e.queries[n])throw'unknown query key "'+n+'" from ismutation feature of group '+t}if(!n.limitsamplebyeitherannotation)throw".limitsamplebyeitherannotation[] missing from group "+t;if(!Array.isArray(n.limitsamplebyeitherannotation))throw".limitsamplebyeitherannotation[] should be array from group "+t;if(0==n.limitsamplebyeitherannotation.length)throw".limitsamplebyeitherannotation[] zero length from group "+t;for(const e of n.limitsamplebyeitherannotation){if(!e.key)throw"key missing from one of limitsamplebyeitherannotation from group "+t;if(!e.value)throw"value missing from one of limitsamplebyeitherannotation from group "+t}}}delete e.annotationsampleset2matrix.commonfeatureattributes}}function $o(e,t){if(e.groupsamplebyattr){e.groupsamplebyattr.key2group=new Map;for(const n in t.cohort.annotation)fo(n,[],e.groupsamplebyattr.key2group,[],t,e)}}function Do(e,t,n){if(e.readcountCutoff&&(!Number.isInteger(e.readcountCutoff)||e.readcountCutoff<1))return"readcountCutoff must be positive integer";let s;if(e.file){const[t,n]=jo(e.file);if(t)return"tabix file error: "+t;e.file=n,s=n}else{if(!e.url)return"no file or url given for mdsjunction "+e.name;s=e.url}const r={encoding:"utf8"};const o=N().execSync(Gr+" -H "+s,r).trim();if(o){const n=o.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const s=n[0].split("\t");if(s[5]){e.samples=s.slice(5),e.attributeSummary=Lo(e.samples,t),e.hierarchySummary=Po(e.samples,t);for(const t in e.hierarchySummary){let n=0;for(const s in e.hierarchySummary[t])n++;console.log(n+" "+t+" hierarchy levels for "+e.name)}}}{const t=N().execSync(Gr+" -l "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=$.contigNameNoChr(n,t.split("\n"))}if(console.log("(mdsjunction) "+e.name+": "+(e.samples?e.samples.length:0)+" samples, "+(e.nochr?'no "chr"':'has "chr"')),!e.infoFilter)return".infoFilter{} missing";if(!e.infoFilter.lst)return".lst[] missing from .infoFilter";for(const t of e.infoFilter.lst){if(!t.key)return".key missing from one of infoFilter";if(!t.label)return".label missing from one of infoFilter";if(!t.categories)return".categories missing from one of infoFilter";for(const e in t.categories){if(!t.categories[e].label)return".label missing from one category of "+t.label;if(!t.categories[e].color)return".color missing from on category of "+t.label}if(t.hiddenCategories){for(const e in t.hiddenCategories)if(!t.categories[e])return"invalid hidden key "+e+" of "+t.label}else t.hiddenCategories={}}if(!e.singlejunctionsummary)return".singlejunctionsummary missing but is currently required from "+e.name;if(e.singlejunctionsummary.readcountboxplotpercohort){if(!e.singlejunctionsummary.readcountboxplotpercohort.groups)return".groups[] missing from query.singlejunctionsummary.readcountboxplotpercohort for "+e.name;for(const t of e.singlejunctionsummary.readcountboxplotpercohort.groups){if(!t.key)return".key missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups";if(!t.label)return".label missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups"}}}function Lo(e,t){if(!(t.cohort&&t.cohort.annotation&&t.cohort.attributes&&e))return;const n={};for(const s of t.cohort.attributes.lst){const r={};for(const e in s.values)r[e]=0;for(const n of e){const e=t.cohort.annotation[n];if(!e)continue;const o=e[s.key];null!=o&&(o in r&&r[o]++)}n[s.key]=r}return n}function Po(e,t){if(!t.cohort||!t.cohort.annotation||!t.cohort.hierarchies||0==e.length)return;const n=[];for(const s of e){const e=t.cohort.annotation[s];e&&n.push(e)}const s={};for(const e of t.cohort.hierarchies.lst){const t=(0,A.N)(n,e.levels),r=he()(t);r.sum((e=>e.value));const o={};r.eachBefore((e=>{o[e.id]=e.value})),s[e.name]=o}return s}function Go(e,t,n){let s;if(e.file){const[t,n]=jo(e.file);if(t)return"tabix file error: "+t;s=n}else{if(!e.url)return"no file or url given for (mdscnv) "+e.name;s=e.url}const r={encoding:"utf8"};const o=N().execSync(Gr+" -H "+s,r).trim();if(o){const n=o.split("\n");if(1!=n.length)return"mdscnv file has multiple header lines (begin with #), but should have just 1";const s=n[0].split("\t");e.samples=s.slice(5),e.attributeSummary=Lo(e.samples,t),e.hierarchySummary=Po(e.samples,t);for(const t in e.hierarchySummary){let n=0;for(const s in e.hierarchySummary[t])n++;console.log(n+" "+t+" hierarchy levels for "+e.name)}}{const t=N().execSync(Gr+" -l 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n=t.queries[e.expressionrank_querykey];if(!n)return"invalid key by expressionrank_querykey";if(!n.isgenenumeric)return"query "+e.expressionrank_querykey+" not tagged as isgenenumeric"}if(e.vcf_querykey){const n=t.queries[e.vcf_querykey];if(!n)return"invalid key by vcf_querykey";if(n.type!=$.tkt.mdsvcf)return"query "+e.vcf_querykey+" not of mdsvcf type"}if(e.groupsamplebyattr){if(!e.groupsamplebyattr.attrlst)return".attrlst[] missing from groupsamplebyattr";if(0==e.groupsamplebyattr.attrlst.length)return"groupsamplebyattr.attrlst[] empty array";if(!t.cohort)return"groupsamplebyattr in use but ds.cohort missing";if(!t.cohort.annotation)return"groupsamplebyattr in use but ds.cohort.annotation missing";t.cohort.sampleAttribute||(t.cohort.sampleAttribute={}),t.cohort.sampleAttribute.attributes||(t.cohort.sampleAttribute.attributes={},console.log("cohort.sampleAttribute added when groupsamplebyattr is in use"));for(const n of e.groupsamplebyattr.attrlst){if(!n.k)return"k missing from one of 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Date.now()-i<k},y.getPayloadFromHeaderAuth=function(e,t){if(!e.headers?.authorization)return{};const n=x(e.query,t);if(!n)return{};const[s,r]=e.headers.authorization.split(" ");if("bearer"!=s.toLowerCase())throw`unsupported authorization type='${s}', allowed: 'Bearer'`;const o=Buffer.from(r,"base64").toString();return a().verify(o,n.secret)||{}}},getJwtPayload:h,canDisplaySampleIds:(e,t)=>!!t.cohort.termdb.displaySampleIds&&y.userCanAccess(e,t),getDsAuth:()=>[],getForbiddenRoutesForDsEmbedder:()=>[],userCanAccess:()=>!0,getRequiredCredForDsEmbedder:()=>{},getPayloadFromHeaderAuth:()=>({})}},7833:(e,t,n)=>{"use strict";n.r(t);var s=n(7147),r=n.n(s),o=n(1017),i=n.n(o),a=(n(3345),n(334)),l=n.n(a),c=n(8907),f=n(8064),u=n(5494),d=n(6733),p=n(5558),m=n(3602),h=n(6279);const g={snvindel:u,sv:h,fusion:h,svjson:n(8423),cnv:d,itd:m,deletion:p,truncation:n(8235)};function y(e,t,n,s,r,o){for(const i of t.yesSamples){if(o&&!o.includes(i))continue;n.has(i)||n.set(i,{sample:i});const t=n.get(i);s in t||(t[s]={key:s,values:[],label:s}),r?t[s].values.some((t=>t.dt==e&&t.origin==r))||t[s].values.push({dt:parseInt(e),class:"WT",_SAMPLEID_:i,origin:r}):t[s].values.some((t=>t.dt==e))||t[s].values.push({dt:parseInt(e),class:"WT",_SAMPLEID_:i})}for(const i of t.noSamples){if(o&&!o.includes(i))continue;n.has(i)||n.set(i,{sample:i});const t=n.get(i);s in t||(t[s]={key:s,values:[],label:s}),r?t[s].values.some((t=>t.dt==e&&t.origin==r))||t[s].values.push({dt:parseInt(e),class:"Blank",_SAMPLEID_:i,origin:r}):t[s].values.some((t=>t.dt==e))||t[s].values.push({dt:parseInt(e),class:"Blank",_SAMPLEID_:i})}}async function b(e,t){const n=e.cohort;try{if(n.mutationFlagSet)return n.mutationFlagSet;if(!n.mutationset)return;const s={},r=e.sampleName2Id;for(const[e,o]of n.mutationset.entries()){const n=await v(e,o,t);s[Math.random()]=n;for(const e in n.data)for(const t of n.data[e])t._SAMPLENAME_=t.sample.split(";")[0].trim(),t._SAMPLEID_=r.get(t._SAMPLENAME_)||t._SAMPLENAME_}return n.mutationFlagSet=s,s}catch(e){throw e}}async function v(e,t,n){const s=f.Dz(n);if(!s)throw"init_bulk_flag() failed";s.tpsetname=t.name?t.name:"set"+e;for(const e in t){if(!(e in g))throw`unknown mutationset: ${e}`;const n=t[e].startsWith("/")?t[e]:i().join(l().tpmasterdir,t[e]);try{const t=(await r().promises.readFile(n,"utf8")).trim().split(/\r?\n/);if(g[e].parseheader(t[0],s))throw`${e} header line error: herr`;for(let n=1;n<t.length;n++)g[e].parseline(n,t[n],s)}catch(e){throw e}}return s}exports.mayGetGeneVariantData=async function(e,t){const n=this,s=e.term.name,r=await b(n,t.genome),o=new Map;if(!r)return o;let i;t?.filter?.lst.length>0&&(i=[...new Set((await(0,c.cf)(t.filter,n)).map((e=>e.id)))]);for(const e in r){const t=r[e];if(s in t.data){for(const e of t.data[s]){const t=e._SAMPLEID_;if(i&&!i.includes(t))continue;o.has(t)||o.set(t,{sample:t});const n=o.get(t);s in n||(n[s]={key:s,values:[],label:s}),n[s].values.push(e)}if(n.assayAvailability?.byDt)for(const e in n.assayAvailability.byDt){const t=n.assayAvailability.byDt[e];if(t.byOrigin)for(const n in t.byOrigin){y(e,t.byOrigin[n],o,s,n,i)}else y(e,t,o,s,!1,i)}}}return o},exports.getTermTypes=async function(e){const t=this;try{const n="string"==typeof e.ids?JSON.parse(e.ids):e.ids,s=n.map((()=>"?")).join(","),r=`SELECT id, name, type, jsondata, parent_id FROM terms WHERE id IN (${s}) OR name IN (${s})`,o=t.cohort.db.connection.prepare(r).all([...n,...n]),i={};for(const e of o)e.jsondata&&Object.assign(e,JSON.parse(e.jsondata)),i[e.id]=e;const a=n.filter((e=>!i[e])),l=await b(t,e.genome);if(l)for(const e in l){const t=l[e];if(t.data)for(const e of a)e in t.data&&!(e in i)&&(i[e]={name:e,type:"geneVariant"})}return i}catch(e){return e.stack&&console.log(e.stack),{error:e.message||e}}},exports.mayGetMatchingGeneNames=async function(e,t,n,s=25){const r=await b(this,n.genome);if(r)for(const n in r){const o=r[n];for(const n in o.data){if(n.length>s)continue;if(!o.data[n]?.length)continue;const r={name:n,type:"geneVariant",isleaf:!0};n===t?e.equals.push(r):n.startsWith(t)?e.startsWith.push(r):n.includes(" "+t)?e.startsWord.push(r):n.includes(t)?e.includes.push(r):"TP53"==n&&0}}},exports.get_flagset=b},4065:(e,t,n)=>{"use strict";function s(e,t){if(e.genomicNameRegexp.test(t.input))throw"invalid character in gene name";if(t.deep){const n={};let s;{const n=e.genedb.getnamebynameorisoform.get(t.input,t.input);n&&(s=n.name)}if(!s&&e.genedb.getNameByAlias){const n=e.genedb.getNameByAlias.get(t.input);n&&(s=n.name)}if(!s&&e.genedb.get_gene2canonicalisoform&&t.input.toUpperCase().startsWith("ENSG")){const r=e.genedb.get_gene2canonicalisoform.get(t.input);if(r&&r.isoform){const t=r.isoform;n.found_isoform=t;const o=e.genedb.getnamebynameorisoform.get(t,t);if(!o)throw"cannot map enst isoform to symbol";s=o.name}}s||(s=t.input);const r=e.genedb.getjsonbyname.all(s);return n.gmlst=r.map((e=>{const t=JSON.parse(e.genemodel);return e.isdefault&&(t.isdefault=!0),t})),n}const n=t.input.toUpperCase(),s=(n.substr(0,2),e.genedb.getnameslike.all(n+"%"));if(s.length)return s.sort(),{hits:s.map((e=>e.name))};if(e.genedb.getNameByAlias){const t=e.genedb.getNameByAlias.all(n);if(t.length)return{hits:t.map((e=>e.name))}}{const n=e.genedb.getnamebynameorisoform.get(t.input,t.input);if(n)return{hits:[n.name]}}return{hits:[]}}n.d(t,{S:()=>s})},2062:(e,t,n)=>{"use strict";n.d(t,{W:()=>a,A:()=>l});var s=n(334),r=n.n(s),o=n(7147),i=n.n(o);async function a(e){l.deps||async function(){const e=`${process.cwd()}/package.json`;try{if(!i().existsSync(e))return;{const t=i().readFileSync(e,{encoding:"utf8"}),n=JSON.parse(t),s=n?.dependencies["@sjcrh/proteinpaint-server"];s&&(l.deps["@sjcrh/proteinpaint-server"].entry=s);const r=n?.dependencies["@sjcrh/proteinpaint-client"];r&&(l.deps.entry["@sjcrh/proteinpaint-client"]||(l.deps["@sjcrh/proteinpaint-client"]={}),l.deps["@sjcrh/proteinpaint-client"]=r)}}catch(e){console.log(e)}}();const t={status:"ok",genomes:{},versionInfo:l};for(const n in e){const s=e[n],r={};if(s.genedb&&(r.genedb={buildDate:s.genedb.get_buildDate?.get().date||"unknown",tables:s.genedb.tableSize}),s.termdbs){r.termdbs={};for(const e in s.termdbs){const t=s.termdbs[e];r.termdbs[e]={buildDate:t.cohort.termdb.q.get_buildDate?.get().date||"unknown"}}}Object.keys(r).length&&t.genomes&&(t.genomes[n]=r)}return t}const l={pkgver:"2.42.2",codedate:function(){const e=i().existsSync(r().binpath+"/server.js")&&i().statSync(r().binpath+"/server.js").mtime||new Date(0),t=i().existsSync("public/bin/proteinpaint.js")&&i().statSync("public/bin/proteinpaint.js").mtime||new Date(0);return(e>t?e:t).toDateString()}(),launchdate:new Date(Date.now()).toString().split(" ").slice(0,5).join(" "),deps:{}},c=`${r().binpath}/package.json`;if(i().existsSync(c)){const e=JSON.parse(i().readFileSync(c,{encoding:"utf8"}));l.deps["@sjcrh/proteinpaint-server"]={installed:e.version}}const f=c.replace("server","client");if(i().existsSync(f)){const e=JSON.parse(i().readFileSync(f,{encoding:"utf8"}));l.deps["@sjcrh/proteinpaint-client"]={installed:e.version}}},9157:(e,t,n)=>{"use strict";n.r(t),n.d(t,{default:()=>c});var s=n(7147),r=n.n(s),o=(n(1017),n(334)),i=n.n(o),a=n(2081),l=n(2781);async function c(e,t,n=[]){try{await r().promises.stat(e)}catch(t){throw`${e} does not exist`}const s=[],o=[];return new Promise(((r,c)=>{const f=(0,a.spawn)(i().Rscript,[e,...n]);if(t&&t.length>0)try{const e=t.join("\n")+"\n";l.Readable.from(e).pipe(f.stdin)}catch(e){f.kill();let t=e;o.length>0&&(t+=`\nR stderr: ${o.join("").trim()}`),c(t)}f.stdout.on("data",(e=>s.push(e))),f.stderr.on("data",(e=>o.push(e))),f.on("error",(e=>c(e))),f.on("close",(e=>{if(0!==e){let t=`R process exited with non-zero status code=${e}`;s.length>0&&(t+=`\nR stdout: ${s.join("").trim()}`),o.length>0&&(t+=`\nR stderr: ${o.join("").trim()}`),c(t)}if(o.length>0){const e=o.join("").trim();c(`R process emitted standard error\nR stderr: ${e}`)}const t=s.join("").trim().split("\n");r(t)}))}))}},901:(e,t,n)=>{"use strict";n.d(t,{T:()=>r,w:()=>o});var s=n(8907);async function r(e,t,n){if(!t)return;const r=function(e,t){{const t=e.filter||e.filterObj;if(t){if(!Array.isArray(t.lst))throw"filterObj.lst is not array";return 0==t.lst.length?null:t}}if(e.tid2value){if("object"!=typeof e.tid2value)throw"q.tid2value{} not object";return o(e.tid2value,t)}}(e,n);if(!r)return;const i=[...new Set((await(0,s.cf)(r,n)).map((e=>e.id)))];let a;a=Number.isInteger(t[0])?new Set(t):new Set(t.map((e=>e.name)));const l=new Set;for(const e of i)a.has(e)&&l.add(e);return l}function o(e,t){const n={type:"tvslst",in:!0,join:"and",lst:[]};for(const s in e){const r=t.cohort.termdb.q.termjsonByOneid(s);if(!r)continue;const o=e[s];n.lst.push({type:"tvs",tvs:{term:r,values:[{key:o}]}})}return n}},1169:(e,t,n)=>{"use strict";n.d(t,{Ak:()=>h,Z5:()=>v,sV:()=>R,eG:()=>b,r8:()=>D,z7:()=>$,ws:()=>I,nD:()=>T,wm:()=>E,IK:()=>x,CN:()=>w,xq:()=>y,vK:()=>g});var s=n(2273),r=n(4048),o=n(6452),i=n.n(o),a=n(1017),l=n.n(a),c=n(4973);function f(e){const t={op:e.in?"and":"not",content:[]};if(!Array.isArray(e.lst))throw"filter.lst[] not array";for(const n of e.lst){if("tvs"!=n.type)throw'filter.lst[] item.type!="tvs"';if(!n.tvs)throw"item.tvs missing";if(!n.tvs.term)throw"item.tvs.term missing";if(n.tvs.values){const e={op:n.tvs.isnot?"!=":"in",content:{field:u(n.tvs.term.id),value:n.tvs.values.map((e=>e.key))}};t.content.push(e)}else{if(!n.tvs.ranges)throw"unknown tvs structure when converting to gdc filter";for(const e of n.tvs.ranges)e.startunbounded?t.content.push({op:e.stopinclusive?n.tvs.isnot?">":"<=":n.tvs.isnot?">=":"<",content:{field:u(n.tvs.term.id),value:e.stop}}):e.stopunbounded?t.content.push({op:e.startinclusive?n.tvs.isnot?"<":">=":n.tvs.isnot?"<=":">",content:{field:u(n.tvs.term.id),value:e.start}}):n.tvs.isnot?t.content.push({op:"or",content:[{op:"and",content:[{op:e.startinclusive?"<":"<=",content:{field:u(n.tvs.term.id),value:e.start}}]},{op:"and",content:[{op:e.stopinclusive?">":">=",content:{field:u(n.tvs.term.id),value:e.stop}}]}]}):t.content.push({op:"and",content:[{op:e.startinclusive?">=":">",content:{field:u(n.tvs.term.id),value:e.start}},{op:e.stopinclusive?"<=":"<",content:{field:u(n.tvs.term.id),value:e.stop}}]})}}return t}function u(e){const t=e.split(".");return"case"==t[0]&&(t[0]="cases"),t.join(".")}n(3345);var d=n(334),p=n.n(d);function m(...e){p().debugmode&&console.log(e.join(" "))}function h(e,t){e.convertSampleId.get=e=>{const n={};for(const s of e)n[s]=t.__gdc.map2caseid.get(s)||s;return n}}async function g(e,t){const n=["consequence.transcript.is_canonical","consequence.transcript.transcript_id"];e.get=async e=>{if(!e.ssm_id)throw".ssm_id missing";const{host:s,headers:r}=t(e),o=await i()(s.rest+"/ssms/"+e.ssm_id+"?fields="+n.join(","),{method:"GET",headers:r});let a;try{a=JSON.parse(o.body)}catch(e){throw"invalid json in response"}if(!a.data||!a.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(a.data.consequence))throw".data.consequence not array";const l=a.data.consequence.find((e=>e.transcript.is_canonical));return l?l.transcript.transcript_id:a.data.consequence[0].transcript.transcript_id}}function y(e){e.queries.snvindel.byrange.get=async t=>await e.queries.snvindel.byisoform.get(t)}function b(e,t){e.queries.geneExpression.get=async n=>{if(!Array.isArray(n.genes))throw"q.genes[] not array";const s=new Map,r=new Date,o=await v(n,e);if(0==o.length)return{gene2sample2value:s,byTermId:{}};const a=new Date;m(o.length,"cases with exp data:",a-r,"ms");const[l,c]=await async function(e,t,n,s,r){const o=[],a=new Map;for(const n of e){const e=n.gene||n.name;if("string"!=typeof e)continue;if(e.startsWith("ENSG")&&15==e.length){o.push(e),a.set(e,e);continue}const s=t.genedb.getAliasByName.all(e);if(Array.isArray(s))for(const t of s)if(t.alias.startsWith("ENSG")){o.push(t.alias),a.set(t.alias,e);break}if(o.length>100)break}try{const{host:e,headers:t}=s.getHostHeaders(r),l=await i().post(`${e.geneExp}/gene_expression/gene_selection`,{headers:t,body:JSON.stringify({case_ids:n,gene_ids:o,selection_size:o.length})}),c=JSON.parse(l.body);if(!Array.isArray(c.gene_selection))throw"re.gene_selection[] not array";const f=[];for(const e of c.gene_selection){if("string"!=typeof e.gene_id)throw".gene_id missing from one of re.gene_selection[]";f.push(e.gene_id)}return[f,a]}catch(e){throw e}}(n.genes,t,o,e,n);if(0==l.length)return{gene2sample2value:s,byTermId:{}};const f=new Date;m(l.length,"out of",n.genes.length,"genes selected for exp:",f-a,"ms");const u={};for(const e of l){const t=c.get(e);u[t]={gencodeId:e},s.set(t,new Map)}const d=await async function(e,t,n,s,r,o){const{host:a,headers:l}=o.getHostHeaders(e),c=await i().post(`${a.geneExp}/gene_expression/values`,{headers:l,body:JSON.stringify({case_ids:n,gene_ids:t,format:"tsv",tsv_units:"uqfpkm"})});if("string"!=typeof c.body)throw"response.body is not tsv text";const f=c.body.trim().split("\n");if(f.length<=1)throw"less than 1 line from tsv response.body";const u=f[0].split("\t").slice(1);if(u.length!=n.length)throw"sample column length != case_ids.length";const d={};for(const e of u){const t=o.__gdc.caseid2submitter.get(e);if(!t)throw"case submitter id unknown for a uuid";d[e]={label:t}}for(let e=1;e<f.length;e++){const t=f[e].split("\t");if(t.length!=u.length+1)throw"number of fields in gene line does not equal header";const n=t[0];if(!n)throw"ensg l[0] missing from a line";const o=s.get(n);if(!o)throw"symbol missing for "+n;for(const[e,n]of u.entries()){const s=Number(t[e+1]);if(!Number.isFinite(s))throw"non-numeric exp value from gdc";r.get(o)[n]=s}}return d}(n,l,o,c,s,e);return m("gene-case matrix built:",new Date-f,"ms"),{gene2sample2value:s,byTermId:u,bySampleId:d}}}async function v(e,t){const n={op:"and",content:[]};e.filter0&&n.content.push(e.filter0),e.filterObj&&n.content.push(f(e.filterObj)),e.filter&&n.content.push(f(e.filter));const s={size:1e4,fields:"case_id"};n.content.length&&(s.case_filters=n);try{const{host:n,headers:r}=t.getHostHeaders(e),o=await i().post(l().join(n.rest,"cases"),{headers:r,body:JSON.stringify(s)}),a=JSON.parse(o.body);if(!Array.isArray(a.data.hits))throw"re.data.hits[] not array";const c=[];for(const e of a.data.hits)if(e.id&&t.__gdc.casesWithExpData.has(e.id)&&(c.push(e.id),1e3==c.length))break;return c}catch(e){throw e.stack&&console.log(e.stack),e}}function w(e){e.queries.snvindel.byisoform.get=async t=>{const n=_(t,e),r=await async function(e,t){const n=L,s=G,{host:r,headers:o}=t.getHostHeaders(e),a=i().post(l().join(r.rest,n.endpoint),{headers:o,body:JSON.stringify(Object.assign({size:n.size,fields:n.fields.join(",")},n.filters(e)))}),c=i().post(l().join(r.rest,s.endpoint),{headers:o,body:JSON.stringify(Object.assign({size:s.size,fields:s.fields.join(",")},s.filters(e,t)))}),[f,u]=await Promise.all([a,c]);let d,p;try{d=JSON.parse(f.body),p=JSON.parse(u.body)}catch(e){throw"invalid JSON returned by GDC"}if(!d.data||!d.data.hits)throw"query1 did not return .data.hits";if(!p.data||!p.data.hits)throw"query2 did not return .data.hits[]";if(!Array.isArray(d.data.hits)||!Array.isArray(p.data.hits))throw"re.data.hits[] is not array";const m=new Map;for(const t of d.data.hits){if(!t.ssm_id)throw"ssm_id missing from a ssms hit";if(!t.consequence)throw".consequence[] missing from a ssm";if(!Number.isInteger(t.start_position))throw"hit.start_position is not integer";let n;t.csqcount=t.consequence.length,n=e.isoform?t.consequence.find((t=>t.transcript.transcript_id==e.isoform)):t.consequence.find((e=>e.transcript.is_canonical)),t.consequence=n||t.consequence[0],t.cases=[],m.set(t.ssm_id,t)}for(const e of p.data.hits){if(!e.ssm)throw".ssm{} missing from a case";if(!e.ssm.ssm_id)throw".ssm.ssm_id missing from a case";const t=m.get(e.ssm.ssm_id);if(!t)throw"ssm_id not found in ssms query";if(!e.case)throw".case{} missing from a case";t.cases.push(e.case)}return[...m.values()]}(t,e),o=[];for(const e of r){const n={ssm_id:e.ssm_id,dt:s.dtsnvindel,chr:e.chromosome,pos:e.start_position-1,ref:e.reference_allele,alt:e.tumor_allele,isoform:t.isoform,csqcount:e.csqcount};if(k(n,e.consequence),!t.hiddenmclass||!t.hiddenmclass.has(n.class)){n.samples=[];for(const s of e.cases){const e={};if(t.gdcUseCaseuuid){if(e.sample_id=s.case_id,!e.sample_id)throw"gdcUseCaseuuid=true but c.case_id undefined"}else if(e.sample_id=s.observation?.[0]?.sample?.tumor_sample_uuid,!e.sample_id)throw"gdcUseCaseuuid=false but c.observation?.[0]?.sample?.tumor_sample_uuid undefined";n.samples.push(e)}o.push(n)}}if(n){t.isoform=n;for(const e of o)e.isoform=n}return o}}function _(e,t){if(!e.isoform)return;let n;if("N"==e.isoform[0]&&t.refseq2ensembl_query){const s=t.refseq2ensembl_query.get(e.isoform);s&&(n=e.isoform,e.isoform=s.ensembl)}return n}function k(e,t){if(t&&t.transcript.consequence_type){const[n,r,o]=s.vepinfo(t.transcript.consequence_type);e.class=r,e.mname=t.transcript.aa_change}e.mname||(e.mname=e.ref+">"+e.alt),e.class||(s.basecolor[e.ref]&&s.basecolor[e.alt]?e.class=s.mclasssnv:"-"==e.ref?e.class=s.mclassinsertion:"-"==e.alt?e.class=s.mclassdeletion:e.class=s.mclassmnv)}function x(e){const t=["cnv.cnv_change","cnv.gene_level_cn","cnv.consequence.gene.symbol","case.submitter_id","case.case_id"];function n(e){const n=t.slice();if(e.twLst)for(const t of e.twLst){let e=t.term.id;e.startsWith("case.")&&(e="occurrence."+e),n.push(e)}return n.join(",")}function r(e){if(!e.gene&&"string"!=typeof e.gene)throw"p.gene does not provide non-empty string";const t={filters:{op:"and",content:[]},case_filters:{op:"and",content:[]}};return e.gene&&t.filters.content.push({op:"=",content:{field:"cnv.consequence.gene.symbol",value:e.gene.split(",")}}),e.filter0&&t.case_filters.content.push(e.filter0),e.filterObj&&t.case_filters.content.push(f("string"==typeof e.filterObj?JSON.parse(e.filterObj):e.filterObj)),t}e.queries.geneCnv.bygene.get=async t=>{const{host:o,headers:a}=e.getHostHeaders(t),c=await i().post(l().join(o.rest,"cnv_occurrences"),{headers:a,body:JSON.stringify(Object.assign({size:1e5,fields:n(t)},r(t)))}),f=JSON.parse(c.body);if(!Array.isArray(f?.data?.hits))throw"geneCnv response body is not {data:hits[]}";const u={ssm_id:"geneCnvGain",dt:s.dtcnv,class:s.mclasscnvgain,samples:[]},d={ssm_id:"geneCnvLoss",dt:s.dtcnv,class:s.mclasscnvloss,samples:[]};for(const e of f.data.hits){if("object"!=typeof e.cnv)throw"hit.cnv{} not obj";if("object"!=typeof e.case)throw"hit.case{} not obj";if(!e.cnv.gene_level_cn)throw"hit.cnv.gene_level_cn is not true";let n;if("Gain"==e.cnv.cnv_change)n=u;else{if("Loss"!=e.cnv.cnv_change)throw"hit.cnv.cnv_change is not Gain/Loss";n=d}const s={sample_id:e.case.case_id};if(t.twLst)for(const n of t.twLst)S(s,e.case,n);n.samples.push(s)}const p=[];return u.samples.length&&p.push(u),d.samples.length&&p.push(d),p}}function N(e,t){if(!t)return;const n=t.split(",");for(const t of n){const n=t.split("--");if(2==n.length)return e.geneA=n[0].split("(")[0],void(e.geneB=n[1].split("(")[0])}}function S(e,t,n){const s=n.term.id.split(".");if(function t(r,o){const i=s[o];if(o==s.length-1)return void(e[n.term.id]?e[n.term.id].add(r[i]):e[n.term.id]=r[i]);const a=r[i];if(null==a)return;if(Array.isArray(a)){e[n.term.id]=new Set;for(const e of a)t(e,o+1);return}t(a,o+1)}(t,1),e[n.term.id]instanceof Set&&(e[n.term.id]=[...e[n.term.id]][0]),n.term.id in e&&"categorical"==n.term.type){const t=function(e,t){if("custom-groupset"==t.q?.type&&Array.isArray(t.q?.groupsetting?.customset?.groups))for(const n of t.q.groupsetting.customset.groups){if(!Array.isArray(n.values))throw"group.values[] not array from tw.q.groupsetting.customset.groups";if(-1!=n.values.findIndex((t=>t.key==e)))return n.name}if("predefined-groupset"==t.q?.type&&Number.isInteger(t.q.groupsetting?.predefined_groupset_idx)&&t.term.groupsetting?.lst[t.q.groupsetting.predefined_groupset_idx])for(const n of t.term.groupsetting.lst[t.q.groupsetting.predefined_groupset_idx]){if(!Array.isArray(n.values))throw"group.values[] not array from tw.term.groupsetting.lst[]";if(-1!=n.values.findIndex((t=>t.key==e)))return n.name}}(e[n.term.id],n);t&&(e[n.term.id]=t)}}function A(e,t){const n={};for(const s of t)if(("integer"==s.term.type||"float"==s.term.type)&&s.q?.mode)if("discrete"==s.q.mode||"binary"==s.q.mode){const t={};for(const n of e){const e=n[s.term.id];Number.isFinite(e)&&("min"in t?(t.min=Math.min(e,t.min),t.max=Math.max(e,t.max)):(t.min=e,t.max=e))}const o=(0,r.gp)(s.q,(e=>t),s.term.valueConversion);for(const e of o)e.name=e.label;n[s.term.id]={bins:o};for(const t of e){const e=t[s.term.id];Number.isFinite(e)&&(t[s.term.id]=C(o,e))}}else if("continuous"!=s.q.mode)throw"mayApplyBinning: unknown numeric q.mode";return n}function C(e,t){for(const n of e)if(n.startunbounded){if(t<n.stop)return n.label;if(n.stopinclusive&&t==n.stop)return n.label}else if(n.stopunbounded){if(t>n.start)return n.label;if(n.startinclusive&&t==n.start)return n.label}else if((t>n.start||t===n.start&&n.startinclusive)&&(t<n.stop||t===n.stop&&n.stopinclusive))return n.label}function j(e){for(const t of e)if(null==t.id||""==t.id){if(!t?.term?.id)throw"tw.id and tw.term are both missing";t.id=t.term.id}else t.term||(t.term={id:t.id})}async function T(e,t,n,s){if(e.isHierCluster)return await async function(e,t,n){const s={op:"and",content:[]};e.filter0&&s.content.push(e.filter0);e.filterObj&&s.content.push(f(e.filterObj));const r=[];for(const e of t){const t=n.cohort.termdb.q.termjsonByOneid(e.term.id);t&&r.push({term:t,q:e.q})}const o=["case_id"],a=new Map;for(const e of r){const t=e.term.id.replace(/^case\./,"");o.push(t),a.set(t,e.term.id)}const{host:c,headers:u}=n.getHostHeaders(e),d=await i().post(l().join(c.rest,"cases"),{headers:u,body:JSON.stringify({size:n.__gdc.casesWithExpData.size,fields:o.join(","),case_filters:s.content.length?s:void 0})}),p=JSON.parse(d.body);if(!Array.isArray(p?.data?.hits))throw"re.data.hits[] not array";const m=[];for(const e of p.data.hits){if("string"!=typeof e.case_id)throw"h.case_id missing";if(!n.__gdc.casesWithExpData.has(e.case_id))continue;const t={sample_id:e.case_id};for(const n of r)S(t,e,n);m.push(t)}const h=A(m,r);return{byTermId:h,samples:m}}(e,t,n);if(j(t),s){if(!Array.isArray(s))throw"geneTwLst not array";e.isoforms=[];for(const t of s){if(!t?.term?.name)throw"gene tw missing .term.name";if(t.term.isoform)e.isoforms.push(t.term.isoform);else{if("object"!=typeof e.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(!e.genome?.genedb?.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const n=e.genome.genedb.get_gene2canonicalisoform.get(t.term.name);if(!n?.isoform)continue;e.isoforms.push(n.isoform)}}}t.some((e=>"case.observation.sample.tumor_sample_uuid"==e.id))||t.push({term:{id:"case.observation.sample.tumor_sample_uuid"}}),t.some((e=>"case.case_id"==e.id))||t.push({term:{id:"case.case_id"}}),"samples"==e.get&&(e.ssm_id_lst||e.isoform)&&(t.some((e=>"ssm.ssm_id"==e.id))||t.push({term:{id:"ssm.ssm_id"}}),t.some((e=>"case.observation.read_depth.t_alt_count"==e.id))||t.push({term:{id:"case.observation.read_depth.t_alt_count"}}),t.some((e=>"case.observation.read_depth.t_depth"==e.id))||t.push({term:{id:"case.observation.read_depth.t_depth"}}),t.some((e=>"case.observation.read_depth.n_depth"==e.id))||t.push({term:{id:"case.observation.read_depth.n_depth"}}));const r=[];for(const e of t){const t=n.cohort.termdb.q.termjsonByOneid(e.term.id);t&&r.push({term:t,q:e.q})}const o=t.map((e=>e.term.id));e.hiddenmclass&&(o.push("ssm.consequence.transcript.consequence_type"),o.push("ssm.consequence.transcript.transcript_id"),o.push("ssm.consequence.transcript.is_canonical")),e.rglst&&(o.push("ssm.chromosome"),o.push("ssm.start_position"));const a={size:1e4,fields:o.join(",")};_(e,n),Object.assign(a,G.filters(e,n));const{host:u,headers:d}=n.getHostHeaders(e),p=await i().post(l().join(u.rest,G.endpoint),{headers:d,body:JSON.stringify(a)});let m;delete e.isoforms;try{m=JSON.parse(p.body)}catch(e){throw"invalid JSON from GDC for variant2samples query"}if(!m.data||!m.data.hits)throw"variant2samples data structure not data.hits[]";if(!Array.isArray(m.data.hits))throw"variant2samples re.data.hits is not array for query";const h=[];for(const t of m.data.hits){if(!t.case)throw"variant2samples .case{} missing from a hit";const s={};if(t.ssm&&(s.ssm_id=t.ssm.ssm_id),e.hiddenmclass){if(!Array.isArray(t.ssm?.consequence))continue;let n;n=e.isoform?t.ssm.consequence.find((t=>t.transcript.transcript_id==e.isoform)):t.ssm.consequence.find((e=>e.transcript.is_canonical));const s={};if(k(s,n||t.ssm.consequence[0]),e.hiddenmclass.has(s.class))continue}if(e.gdcUseCaseuuid){if(s.sample_id=t.case.case_id,!s.sample_id)throw"querySamples_gdcapi: case.case_id missing"}else{const e=t.case?.observation?.[0]?.sample?.tumor_sample_uuid;if(!e)throw"querySamples_gdcapi: aliquot_id missing";s.sample_id=await n.__gdc.aliquot2submitter.get(e),s.sample_URLid=t.case.case_id+"?bioId="+e}for(const e of r)S(s,t.case,e);M(t.case,s),O(s,n),h.push(s)}const g=A(h,r);if(s){const e={gene:s.map((e=>e.term.name)).join(","),twLst:r},t=await n.queries.geneCnv.bygene.get(e);for(const e of t)for(const t of e.samples)h.push(t)}const y=new Map;for(const e of h)(0,c.z9)([e],y,e.ssm_id);return{byTermId:g,samples:[...y.values()]}}function M(e,t){if(!e.observation)return;const n=e.observation[0];n&&n.read_depth&&(t.formatK2v={TumorAC:n.read_depth.t_depth-n.read_depth.t_alt_count+","+n.read_depth.t_alt_count,NormalDepth:n.read_depth.n_depth})}function O(e,t){const n=e["case.project.project_id"];n&&(e.caseIsOpenAccess=t.__gdc.gdcOpenProjects?.has(n))}async function I(e,t,n,s){j(e);const r=[];for(const t of e)t.term&&"categorical"==t.term.type&&r.push({id:t.id,path:t.id.replace("case.","").replace(/\./g,"__"),type:t.term.type});const o=function(e){const t=[];for(const n of e)if(n.id)if(n.type="categorical")t.push(n.path+" {buckets { doc_count, key }}");else{if("integer"!=n.type&&"float"!=n.type)throw"unknown term type";t.push(n.path+" {stats { count }}")}const n=`query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (case_filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\t${t.join("\n")}\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t}`;return n}(r),a=function(e,t){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};z(e?.tid2value,n.filters.content,t),e&&e.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:e.ssm_id_lst.split(",")}});e.filter0&&n.filters.content.push(e.filter0);e.filterObj&&n.filters.content.push(f(e.filterObj));return n}(t,s),{host:l,headers:c}=s.getHostHeaders(t),u=await i().post(l.graphql,{headers:c,body:JSON.stringify({query:o,variables:a})});let d;try{d=JSON.parse(u.body)}catch(e){throw"invalid JSON from GDC for cohortTotal for query :"+o+" and filter: "+filter}const p=["data","explore","cases","aggregations"];let m=d[p[0]];for(let e=1;e<p.length;e++)if(m=m[p[e]],!m)throw`.${p[e]} missing from data structure of termid2totalsize2 for query :${o} and filter: ${filter}`;for(const e of r){if("categorical"==e.type&&!Array.isArray(m[e.path].buckets))throw p.join(".")+" not array for query :"+o+" and filter: "+filter;if(("integer"==e.type||"float"==e.type)&&"object"!=typeof m[e.path].stats)throw p.join(".")+" not object for query :"+o+" and filter: "+filter}const h=new Map;for(const e of r)if("categorical"==e.type){const t=m[e.path].buckets,n=[];for(const e of t)n.push([e.key.replace(".","__"),e.doc_count]);h.set(e.id,n)}else if("integer"==e.type||"float"==e.type){const t=m[e.path].stats.count;h.set(e.id,{total:t})}return n?[h,n]:h}function E(e){const t=["consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change"];e.queries.snvindel.m2csq.get=async n=>{const{host:s,headers:r}=e.getHostHeaders(n),o=await i()(s.rest+"/ssms/"+n.ssm_id+"?fields="+t.join(","),{method:"GET",headers:r});let a;try{a=JSON.parse(o.body)}catch(e){throw"invalid json in response"}if(!a.data||!a.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(a.data.consequence))throw".data.consequence not array";return a.data.consequence.map((e=>e.transcript))}}function R(e,t){e.queries.singleSampleMutation.get=async t=>{if(t.sample.startsWith("___")){const e=t.sample.substring(3);if(!e)throw"expecting uuid after prefix but got blank";t.case_id=e}else e.__gdc.caseid2submitter.has(t.sample)?t.case_id=t.sample:(t.case_id=e.__gdc.map2caseid.get(t.sample),t.case_id||(t.case_id=await F(t.sample,e)));return await async function(e,t,n){const r={mlst:[],dt2total:[]};{const{host:n,headers:o}=t.getHostHeaders(e),a=await i().post(l().join(n.rest,L.endpoint),{headers:o,body:JSON.stringify({size:1e4,fields:L.fields.join(","),filters:L.filters(e).filters})}),c=JSON.parse(a.body);if(!Number.isInteger(c.data?.pagination?.total))throw"re.data.pagination.total not integer";if(!Array.isArray(c.data?.hits))throw"re.data.hits[] not array";c.data.hits.length<c.data.pagination.total&&r.dt2total.push({dt:1,total:c.data.pagination.total});for(const e of c.data.hits){let t=e.consequence.find((e=>1==e.transcript.is_canonical));t||(t=e.consequence[0]);const n=t.transcript.aa_change||t.transcript.consequence_type,[o,i,a]=s.vepinfo(t.transcript.consequence_type);r.mlst.push({dt:s.dtsnvindel,mname:n,class:i,gene:t.transcript.gene.symbol,chr:e.chromosome,pos:e.start_position,ref:e.reference_allele,alt:e.tumor_allele})}}{const n=await async function(e,t){const{host:n,headers:r}=t.getHostHeaders(e),o=await i().post(l().join(n.rest,"files"),{headers:r,body:JSON.stringify({size:1e4,fields:["cases.samples.sample_type","data_type","file_id","data_format","experimental_strategy","analysis.workflow_type"].join(","),filters:function(e){if(!e.case_id)throw".case_id missing";return{op:"and",content:[{op:"in",content:{field:"cases.case_id",value:[e.case_id]}},{op:"in",content:{field:"data_type",value:["Masked Copy Number Segment","Copy Number Segment","Transcript Fusion"]}}]}}(e)})}),a=JSON.parse(o.body);if(!Array.isArray(a.data.hits))throw"re.data.hits[] not array";let c,f,u;for(const e of a.data.hits)if("BEDPE"!=e.data_format){if("TXT"==e.data_format){if("Genotyping Array"==e.experimental_strategy){const t=e.cases?.[0].samples?.[0]?.sample_type;if(!t)continue;if(t.includes("Normal"))continue;if("Masked Copy Number Segment"!=e.data_type)continue;c=e.file_id;continue}if("WGS"==e.experimental_strategy){if(!e.file_id)continue;if("Copy Number Segment"!=e.data_type)continue;f=e.file_id;continue}}}else{if("RNA-Seq"!=e.experimental_strategy)continue;if("Arriba"!=e.analysis?.workflow_type)continue;if("Transcript Fusion"!=e.data_type)continue;u=e.file_id}const d=[];if(f){const e=(await i()(l().join(n.rest,"data")+"/"+f,{method:"GET",headers:r})).body.split("\n");for(let t=1;t<e.length;t++){const n=e[t].split("\t");if(7!=n.length)continue;const r=Number(n[4]),o=Number(n[5]),i=Number(n[6]);if(Number.isNaN(r)||Number.isNaN(o)||Number.isNaN(i))continue;const a={dt:s.dtcnv,chr:n[1],start:Number(n[2]),stop:Number(n[3]),value:r};!a.chr||Number.isNaN(a.start)||Number.isNaN(a.stop)||(d.push(a),r>0&&0==i&&o>0&&d.push({dt:s.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(c){const e=(await i()(l().join(n.rest,"data")+"/"+c,{method:"GET",headers:r})).body.split("\n");for(let t=1;t<e.length;t++){const n=e[t].split("\t");if(6!=n.length)continue;if(!n[1])continue;const r={dt:s.dtcnv,chr:"chr"+n[1],start:Number(n[2]),stop:Number(n[3]),value:Number(n[5])};Number.isNaN(r.start)||Number.isNaN(r.stop)||Number.isNaN(r.value)||d.push(r)}}if(u)try{const e=(await i()(l().join(n.rest,"data")+"/"+u,{method:"GET",headers:r})).body.split("\n");for(let t=1;t<e.length;t++){const n=e[t].split("\t"),r={dt:s.dtfusionrna,chrA:n[0],posA:Number(n[1]),chrB:n[3],posB:Number(n[4])};r.chrA&&r.chrB&&!Number.isNaN(r.posA)&&!Number.isNaN(r.posB)&&(N(r,n[6]),d.push(r))}}catch(e){}return d}(e,t);r.mlst.push(...n)}return r}(t,e)}}async function F(e,t){const{host:n,headers:s}=t.getHostHeaders(q),r=await i().post(`${n.rest}/cases`,{headers:s,body:JSON.stringify({size:1,fields:"case_id,submitter_id",filters:{op:"or",content:[{op:"=",content:{field:"samples.portions.analytes.aliquots.aliquot_id",value:[e]}},{op:"=",content:{field:"submitter_id",value:[e]}},{op:"=",content:{field:"samples.submitter_id",value:[e]}}]}})}),o=JSON.parse(r.body);for(const e of o.data.hits)if(e.case_id)return e.case_id;throw"cannot convert to case_id (uuid)"}function $(e,t){e.queries.singleCell.samples.get=async t=>{const n={op:"and",content:[]};t.filter0&&n.content.push(t.filter0);const s={filters:{op:"and",content:[{op:"=",content:{field:"data_format",value:"tsv"}},{op:"=",content:{field:"data_type",value:"Single Cell Analysis"}},{op:"=",content:{field:"experimental_strategy",value:"scRNA-Seq"}}]},case_filters:n,size:100,fields:["id","cases.submitter_id","cases.project.project_id","cases.samples.sample_type","cases.samples.submitter_id","cases.primary_site","cases.disease_type"].join(",")},{host:r,headers:o}=e.getHostHeaders(t),a=await i().post(l().join(r.rest,"files"),{headers:o,body:JSON.stringify(s)});let c;try{c=JSON.parse(a.body)}catch(e){throw"invalid JSON from "+api.endpoint}if(!Number.isInteger(c.data?.pagination?.total))throw"re.data.pagination.total is not int";if(!Array.isArray(c.data?.hits))throw"re.data.hits[] not array";const f=new Map;for(const e of c.data.hits){if(!e.id)throw"h.id (fileId) missing";const t=e.id,n=e.cases?.[0];if(!n)throw"h.cases[0] missing";const s=n.submitter_id;if(f.has(s)||f.set(s,{sample:s,primarySite:n.primary_site,diseaseType:n.disease_type,projectId:n.project?.project_id,files:[]}),!n.samples?.[0])throw"h.cases[0].samples[0] missing";f.get(s).files.push({fileId:t,sampleName:n.samples[0].submitter_id,sampleType:n.samples[0].sample_type})}return{samples:[...f.values()],fields:e.queries.singleCell.samples.fields,columnNames:e.queries.singleCell.samples.columnNames}}}function D(e,t){e.queries.singleCell.data.get=async t=>{const{host:n,headers:s}=e.getHostHeaders(t),r=(await i()(l().join(n.rest,"data",t.sample),{method:"GET",headers:s})).body.trim().split("\n"),o={name:"UMAP",cells:[],colorBy:"Cluster"},a={name:"TSNE",cells:[],colorBy:"Cluster"},c={name:"PCA",cells:[],colorBy:"Cluster"},f={id:"cluster",name:"Seurat cluster",type:"categorical",values:{}},u={[f.id]:{}};for(let e=1;e<r.length;e++){const t=r[e],n=t.split("\t"),s=n[0];if(!s)throw"cellId missing from a line: "+t;const i=n[3];if(!i)throw"seuratCluster missing from a line";f.values[i]={label:"Cluster "+i},u[f.id][s]=`Cluster ${i}`;const l=Number(n[4]),d=Number(n[5]),p=Number(n[9]),m=Number(n[10]),h=Number(n[14]),g=Number(n[15]);if(Number.isNaN(l))throw"umap1 is nan";if(Number.isNaN(d))throw"umap2 is nan";if(Number.isNaN(p))throw"tsne1 is nan";if(Number.isNaN(m))throw"tsne2 is nan";if(Number.isNaN(h))throw"pc1 is nan";if(Number.isNaN(g))throw"pc2 is nan";const y=`Cluster ${i}`;o.cells.push({cellId:s,x:l,y:d,category:y}),a.cells.push({cellId:s,x:p,y:m,category:y}),c.cells.push({cellId:s,x:h,y:g,category:y})}return{plots:[a,o,c],terms:[f],tid2cellvalue:u}}}const L={endpoint:"/ssms",size:1e5,fields:["ssm_id","chromosome","start_position","reference_allele","tumor_allele","consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change","consequence.transcript.gene.symbol","consequence.transcript.is_canonical"],filters:e=>{const t={filters:{op:"and",content:[]},case_filters:{op:"and",content:[]}};let n;if(e.rglst&&(n=e.rglst[0],P(n)),e.isoform){if("string"!=typeof e.isoform)throw".isoform value not string";t.filters.content.push({op:"=",content:{field:"consequence.transcript.transcript_id",value:[e.isoform]}}),n&&(t.filters.content.push({op:">=",content:{field:"start_position",value:n.start}}),t.filters.content.push({op:"<=",content:{field:"start_position",value:n.stop}}))}else if(n)t.filters.content.push({op:"=",content:{field:"chromosome",value:n.chr}}),t.filters.content.push({op:">=",content:{field:"start_position",value:n.start}}),t.filters.content.push({op:"<=",content:{field:"start_position",value:n.stop}});else{if(!e.case_id)throw".isoform, .rglst, and .case_id are all missing";if("string"!=typeof e.case_id)throw".case_id value not string";t.filters.content.push({op:"=",content:{field:"cases.case_id",value:[e.case_id]}})}if(e.set_id){if("string"!=typeof e.set_id)throw".set_id value not string";t.case_filters.content.push({op:"in",content:{field:"cases.case_id",value:[e.set_id]}})}return e.filter0&&t.case_filters.content.push(e.filter0),e.filterObj&&t.case_filters.content.push(f(e.filterObj)),t}};function P(e){if("object"!=typeof e)throw"p.rglst[0] not object";if("string"!=typeof e.chr||!e.chr||!Number.isInteger(e.start)||!Number.isInteger(e.stop))throw"p.rglst[0] not valid {chr,start,stop}"}const G={endpoint:"/ssm_occurrences",size:1e5,fields:["ssm.ssm_id","case.case_id","case.submitter_id","case.observation.sample.tumor_sample_uuid"],filters:(e,t)=>{const n={filters:{op:"and",content:[]},case_filters:{op:"and",content:[]}};let s=!1;if(e.ssm_id_lst){if("string"!=typeof e.ssm_id_lst)throw"ssm_id_lst not string";n.filters.content.push({op:"=",content:{field:"ssm.ssm_id",value:e.ssm_id_lst.split(",")}}),s=!0}else if(e.isoform)n.filters.content.push({op:"=",content:{field:"ssms.consequence.transcript.transcript_id",value:[e.isoform]}}),s=!0;else if(e.isoforms){if(!Array.isArray(e.isoforms))throw".isoforms[] not array";n.filters.content.push({op:"in",content:{field:"ssms.consequence.transcript.transcript_id",value:e.isoforms}}),s=!0}{let t;if(e.rglst&&(t=e.rglst[0],P(t)),s)t&&(n.filters.content.push({op:">=",content:{field:"ssms.start_position",value:t.start}}),n.filters.content.push({op:"<=",content:{field:"ssms.start_position",value:t.stop}}));else{if(!t)throw".ssm_id_lst, .isoform, .isoforms, .rglst[] are all missing";n.filters.content.push({op:"=",content:{field:"ssms.chromosome",value:t.chr}}),n.filters.content.push({op:">=",content:{field:"ssms.start_position",value:t.start}}),n.filters.content.push({op:"<=",content:{field:"ssms.start_position",value:t.stop}})}}if(e.set_id){if("string"!=typeof e.set_id)throw".set_id value not string";n.case_filters.content.push({op:"in",content:{field:"cases.case_id",value:[e.set_id]}})}return e.filter0&&n.case_filters.content.push(e.filter0),e.filterObj&&n.case_filters.content.push(f(e.filterObj)),z(e.tid2value,n.case_filters.content,t),n}};function z(e,t,n){if(e)for(const s in e){const r=n.cohort.termdb.q.termjsonByOneid(s);if(!r)continue;const o=s.replace(/^case\./,"cases.");if("categorical"==r.type)t.push({op:"in",content:{field:o,value:[e[s]]}});else if("integer"==r.type)for(const n of e[s])t.push({op:n.op,content:{field:o,value:n.range}})}}},4973:(e,t,n)=>{"use strict";n.d(t,{z9:()=>p,dq:()=>u,uK:()=>d});var s=n(1881),r=n(1169),o=n(8877),i=n(7011);async function a(e,t){const n=[];let s=null,r=null;for(const o of t.map((t=>t[e.id]))){if(e.values?.[o]?.uncomputable)continue;const t=Number(o);Number.isFinite(t)&&(n.push(t),null===s?s=r=t:(s=Math.min(s,t),r=Math.max(r,t)))}const a=(0,o.Z)().domain([s,r]).range([10,510]),l=(0,i.q)(a,{values:n},!0,20);if(!Array.isArray(l.bins))throw"getBinsDensity does not return []";if(0==l.bins.length)throw"getBinsDensity returns an empty array";return{minvalue:s,maxvalue:r,densityMax:l.densityMax,density:l.bins,samplecount:n.length,unit:e.unit,ticks:20}}n(3345);var l=n(2273),c=n(4065),f=n(2974);const u=".";function d(e){const t=e.variant2samples;if(t){if(t.type_samples="samples",t.type_sunburst="sunburst",t.type_summary="summary",!t.variantkey)throw".variantkey missing from variant2samples";if(-1==["ssm_id"].indexOf(t.variantkey))throw"invalid value of variantkey";if(t.twLst){if(!Array.isArray(t.twLst))throw"variant2samples.twLst[] is not array";if(0==t.twLst.length)throw"variant2samples.twLst[] empty array";if(!e.cohort||!e.cohort.termdb)throw"ds.cohort.termdb missing when variant2samples.twLst is in use";for(const n of t.twLst){if(!n.id)throw"tw.id missing from one of variant2samples.twLst[]";const t=e.cohort.termdb.q.termjsonByOneid(n.id);if(!t)throw"term not found for one of variant2samples.twLst: "+n.id;if(n.term=t,!n.q)throw"tw.q{} missing for one of variant2samples.twLst: "+n.id}}if(t.sunburst_twLst){if(!Array.isArray(t.sunburst_twLst))throw".sunburst_twLst[] not array from variant2samples";if(0==t.sunburst_twLst.length)throw".sunburst_twLst[] empty array from variant2samples";if(!e.cohort||!e.cohort.termdb)throw"ds.cohort.termdb missing when variant2samples.sunburst_twLst is in use";for(const n of t.sunburst_twLst){if(!n.id)throw"tw.id missing from one of variant2samples.sunburst_twLst[]";const t=e.cohort.termdb.q.termjsonByOneid(n.id);if(!t)throw"term not found for one of variant2samples.sunburst_twLst: "+n.id;if(n.term=t,!n.q)throw"tw.q{} missing for one of variant2samples.sunburst_twLst: "+n.id}}if(t.gdcapi);else{let t=!1;if(e.queries?.snvindel?.byrange?._tk?.samples&&(t=!0),e.queries?.svfusion?.byrange?.samples&&(t=!0),!t)throw"cannot find a sample source from ds.queries{}"}t.get=async t=>await async function(e,t){!function(e,t){if("samples"==e.get){const n=t.queries?.snvindel?.byrange;n&&(n.bcffile||n.chr2bcffile)&&n._tk.format&&(e.addFormatValues=!0)}}(e,t);const n=await async function(e,t){const n=e.twLst?e.twLst.slice():[];if(t.variant2samples.gdcapi)return await(0,r.nD)(e,n,t,e.geneTwLst);if(e.ssm_id_lst)return await async function(e,t,n){const s=new Map;for(const t of e.ssm_id_lst.split(",")){const r=t.split(u);if(4!=r.length){if(6!=r.length)throw"unknown format of ssm id";{if(!n.queries.svfusion||!n.queries.svfusion.byrange)throw"queries.svfusion.byrange missing when id has 6 fields";const[t,o,i,a,c,f]=r,u=decodeURIComponent(f),d=Number(t);if(d!=l.dtsv&&d!=l.dtfusionrna)throw"dt not sv/fusion";const m=Number(i);if(Number.isNaN(m))throw"position not integer";const h=Number(c);if(Number.isNaN(h))throw"pairlstIdx not integer";const g=Object.assign({},e,{rglst:[{chr:o,start:m,stop:m+1}]}),y=await n.queries.svfusion.byrange.get(g);for(const e of y)e.dt==d&&e.pos==m&&e.strand==a&&e.pairlstIdx==h&&e.mname==u&&p(e.samples,s,e.ssm_id)}}else{if(!n.queries.snvindel||!n.queries.snvindel.byrange)throw"queries.snvindel.byrange missing when id has 4 fields";const[t,o,i,a]=r,l=Number(o);if(Number.isNaN(l))throw"no integer position for snvindel from ssm id";const c=Object.assign({},e,{rglst:[{chr:t,start:l,stop:l}]}),f=await n.queries.snvindel.byrange.get(c);for(const e of f)e.pos==l&&e.ref==i&&e.alt==a&&p(e.samples,s,e.ssm_id)}}return m(s,t,n),{samples:[...s.values()]}}(e,n,t);if(e.rglst)return await h(e,n,t);if(e.geneTwLst){if("object"!=typeof e.genome)throw"serverside genome obj needed";e.rglst=[];for(const t of e.geneTwLst)if(t.term.chr&&t.term.start&&t.term.stop)e.rglst.push({chr:t.term.chr,start:t.term.start,stop:t.term.stop});else{const n=c.S(e.genome,{deep:1,input:t.term.name});if(n.gmlst){const t=n.gmlst[0];e.rglst.push({chr:t.chr,start:t.start,stop:t.stop})}}const s=await h(e,n,t);return delete e.rglst,{samples:s}}if(!t?.cohort?.termdb)throw"unable to do sql query: .cohort.termdb missing for ds";const s={ds:t,filter:e.filter||e.filterObj},o=await(0,f.gh)(s,e.twLst),i=[];for(const t in o.samples){const n=o.samples[t];n.sample_id=n.sample,delete n.sample;for(const t of e.twLst)n[t.term.id]&&(n[t.term.id]=n[t.term.id].key);i.push(n)}return{samples:i}}(e,t);if(e.get==t.variant2samples.type_samples)return!e.useIntegerSampleId&&t?.cohort?.termdb?.q?.id2sampleName&&n.samples.forEach((e=>e.sample_id=t.cohort.termdb.q.id2sampleName(e.sample_id))),n;if(e.get==t.variant2samples.type_sunburst)return n.nodes=await async function(e,t,n){const r=(0,s.N)(e,n.twLst.map((e=>({k:e.id}))));for(const e of r)delete e.lst;if(t?.cohort?.termdb?.termid2totalsize2){const e=await async function(e,t,n,s){if(0==e.length)throw"zero terms for crosstab";if(e.length>3)throw"crosstab will not work with more than 3 levels";const r=[],o=new Map;for(const t of e)o.set(t.id,new Set);const i=!s;if(s)for(const n of 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I(e,t,n){const[s,r]=t.groups;M(e,n,s);const o=n.map((e=>e.nm_axis_value));M(e,n,r);for(const[e,t]of n.entries())t.nm_axis_value=o[e]-t.nm_axis_value}function E(e,t,n,s){const r=[];for(const o of t.groups)if("info"!=o.type)if("filter"!=o.type){if("population"!=o.type)throw"unknown group.type";{if(!o.key)throw"group.key missing for type=population";const t=e.queries.snvindel.populations.find((e=>e.key==o.key));if(!t)throw"invalid group.key for population";const i=new Map;for(const e of t.sets)i.set(e.key,{ACraw:Number(n.info[e.infokey_AC]||0),ANraw:Number(n.info[e.infokey_AN]||0)});let a=0,l=0;if(o.adjust_race)[a,l]=R(i,s);else for(const e of i.values())l+=e.ACraw,a+=e.ANraw-e.ACraw;r.push({altCount:l,refCount:a})}}else r.push({altCount:n._altCount,refCount:n._refCount});else{if(!o.key)throw"group.key missing for type=info";r.push({value:n.info[o.key]})}return r}function R(e,t){let n=0;for(const t of e.values())n+=t.ANraw;let s=0,r=0;for(const[o,i]of 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async function(e,t,n,s,r){const o={equals:[],startsWith:[],startsWord:[],includes:[]},i=decodeURIComponent(e.findterm).toUpperCase(),a=[];try{if("snp"==e.targetType){if(!s.queries?.snvindel?.allowSNPs)throw"this dataset does not support snp search";const e=await(0,D.SC)({byName:!0,lst:[i.toLowerCase()]},r);for(const t of e)a.push({type:"geneVariant",name:t.name,subtype:"snp",chr:t.chrom,start:t.chromStart,stop:t.chromEnd,alleles:t.alleles})}else{const t=(0,q.CG)({type:"geneVariant"},e.usecase).has("plot");if(s.mayGetMatchingGeneNames&&t&&await s.mayGetMatchingGeneNames(o,i,e),s.queries?.defaultBlock2GeneMode&&t)try{const e=(0,$.S)(r,{input:i});if(Array.isArray(e.hits))for(let t=0;t<7&&e.hits[t];t++)a.push({name:e.hits[t],type:"geneVariant"})}catch(e){}}const l=await n.q.findTermByName(i,L,e.cohortStr,e.treeFilter,e.usecase,o);a.push(...l.map(z));a.forEach((e=>{"geneVariant"!=e.type&&(e.__ancestors=n.q.getAncestorIDs(e.id),e.__ancestorNames=n.q.getAncestorNames(e.id))})),t.send({lst:a})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}}(s,n,l,o,r);if(s.getterminfo)return function(e,t,n){if(!e.tid)throw"no term id";t.send({terminfo:n.q.getTermInfo(e.tid)})}(s,n,l);if(s.phewas)return s.update?await f.update_image(s,n):s.getgroup?await f.getgroup(s,n):await f.trigger(s,n,o);if(s.gettermdbconfig)return a(s,n,o,r);if(s.getcohortsamplecount)return n.send({count:o.cohort.termdb.q.getcohortsamplecount(s.cohort)});if(s.getsamplecount)return n.send(await async function(e,t,n){const s=i.i.canDisplaySampleIds(e,n);if("list"==t.getsamplecount){return await c.cf(t.filter,n,s)}return await c.B9(t,n)}(t,s,o));if(s.getsamples)return await async function(e,t,n){const s=await c.cf(e.filter,n),r=s.map((e=>n.cohort.termdb.q.id2sampleName(e)));t.send({samples:r})}(s,n,o);if(s.getcuminc)return await async function(e,t,n){const s=await(0,u.g)(e,n);t.send(s)}(s,n,o);if(s.getsurvival)return await async function(e,t,n){const s=await v(e,n);t.send(s)}(s,n,o);if(s.getregression)return await async function(e,t,n){const s=await(0,_.j)(e,n);t.send(s)}(s,n,o);if(s.validateSnps)return n.send(await(0,k.G)(s,l,o,r));if(s.getvariantfilter)return function(e,t){if(t.track)return void e.send(t.track.variant_filter);e.send(t?.queries?.snvindel?.variant_filter||{})}(n,o);if(s.getLDdata)return await async function(e,t,n){if(!e.ldtkname)throw".ldtkname missing";if(!t.queries?.ld?.tracks)throw"no ld tk";const s=t.queries.ld.tracks.find((t=>t.name==e.ldtkname));if(!s)throw"unknown ld tk";if("object"!=typeof e.m)throw"q.m{} not object";if(!e.m.chr)throw"q.m.chr missing";if(!Number.isInteger(e.m.pos))throw"q.m.pos not integer";if(!e.m.ref||!e.m.alt)throw"q.m{} invalid alleles";const r=e.m.ref+"."+e.m.alt,o=(s.nochr?e.m.chr.replace("chr",""):e.m.chr)+":"+e.m.pos+"-"+(e.m.pos+1),i=[];await(0,h.UE)({args:[s.file,o],dir:s.dir,callback:t=>{const n=t.split("\t"),s=Number.parseInt(n[1]),o=Number.parseInt(n[2]),a=n[3],l=n[4],c=Number.parseFloat(n[5]);s==e.m.pos&&a==r?i.push({pos:o,alleles:l,r2:c}):o==e.m.pos&&l==r&&i.push({pos:s,alleles:a,r2:c})}}),n.send({lst:i})}(s,o,n);if(s.genesetByTermId)return function(e,t,n){if(!n.termMatch2geneSet)throw"this feature is not enabled";if("string"!=typeof e.genesetByTermId||0==e.genesetByTermId.length)throw"invalid query term id";const s=n.q.getGenesetByTermId(e.genesetByTermId);t.send(s)}(s,n,l);if(s.getSampleScatter&&(s.for="scatter"),"scatter"==s.for)return await(0,x.uR)(t,s,n,o,r);if(s.getLowessCurve)return await(0,x.v8)(t,s,n);if(s.getCohortsData)return await async function(e,t,n){const s=function(e){const t=e.cohort.db.connection.prepare("select * from features").all();return{cohorts:e.cohort.db.connection.prepare("select * from cohorts where cohort in (select distinct(cohort) from cohort_features)\n\t\t order by sample_count desc").all(),features:t,cfeatures:e.cohort.db.connection.prepare("select * from cohort_features").all()}}(n);t.send(s)}(0,n,o);if("mds3queryDetails"==s.for)return function(e,t){const n={},s=t.queries||{};s.snvindel&&(n.snvindel={},s.snvindel.details&&(n.snvindel.details=s.snvindel.details),s.snvindel.populations&&(n.snvindel.populations=s.snvindel.populations));s.trackLst&&(n.trackLst=s.trackLst);if(s.ld){n.ld=JSON.parse(JSON.stringify(s.ld));for(const e of n.ld.tracks)delete e.file}e.send(n)}(n,o);if("termTypes"==s.for)return n.send(await o.getTermTypes(s));if("matrix"==s.for)return await async function(e,t,n,s,r){if(e.getPlotDataByName){if(!s.cohort?.matrixplots?.plots)throw"ds.cohort.matrixplots.plots missing for the dataset";const t=s.cohort.matrixplots.plots.find((t=>t.name===e.getPlotDataByName));if(!t)throw"invalid name of premade matrix plot";return void n.send(t.matrixConfig)}const o=await(0,m.Yu)(e,s,r);if(i.i.canDisplaySampleIds(t,s))for(const e of Object.values(o.samples))e.sampleName=s.sampleId2Name.get(e.sample);n.send(o)}(s,t,n,o,r);if("getSamplesPerFilter"==s.for)return await(0,m.fZ)(s,o,n);if("mds3variantData"==s.for)return await A(s,n,o);if(s.for,"convertSampleId"==s.for)return function(e,t,n){if(!n.convertSampleId)throw"not supported on this ds";if(!Array.isArray(e.inputs))throw"q.inputs[] not array";t.send({mapping:n.convertSampleId.get(e.inputs)})}(s,n,l);if("singleSampleData"==s.for)return async function(e,t,n,s,r){const o=i.i.canDisplaySampleIds(t,s);let a=[];if(o)try{a=r.q.getSingleSampleData(e.sampleId,e.term_ids),n.send(a)}catch(e){n.send({error:e.message||e})}else n.send({error:"Requires sign in to access the sample data"})}(s,t,n,o,l);if("getProfileFacilities"==s.for)return async function(e,t,n,s,r){const o=i.i.canDisplaySampleIds(t,s);let 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q(e,t,n){if(!e.q.restrictAncestry)return;if(!("name"in e.q.restrictAncestry))throw".name missing from tw.q.restrictAncestry";if(!n.cohort.termdb.restrictAncestries)throw"ds.cohort.termdb.restrictAncestries missing";const s=n.cohort.termdb.restrictAncestries.find((t=>t.name==e.q.restrictAncestry.name));if(!s)throw"unknown ancestry for restriction: "+e.q.restrictAncestry.name;if(s.pcs)e.q.restrictAncestry.pcs=s.pcs;else{if(!s.PCBySubcohort)throw"unknown way of accessing pcs from ds.cohort.termdb.restrictAncestries: "+e.q.restrictAncestry.name;{if(!t.filter)throw"q.filter missing while trying to access subcohort for PCBySubcohort";const n=I(t.filter,"cohortFilter");if(!n)throw"tvs by tag=cohortFilter missing from q.filter.lst[] while trying to access subcohort for PCBySubcohort";const r=n.tvs.values.map((e=>e.key)).sort().join(","),o=s.PCBySubcohort[r];if(!o)throw"unknown key for PCBySubcohort: "+r;if(!o.pcs)throw"pcs Map() missing from PCBySubcohort[]: 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t={},[s,r]=e.shift().split(":");t.term1=n[s],t.term2=n[r],t.lst=e,o.data.type3.interactions.push(t)}else{const t=n[e.shift()];o.data.type3.terms[t]||(o.data.type3.terms[t]=e)}if(o.data.type3.label="Type III statistics",i.totalSnpEffect){if(1!=i.totalSnpEffect.rows.length)throw"total SNP effect table should have 1 row";o.data.totalSnpEffect={header:i.totalSnpEffect.header.slice(0,4)};const e=i.totalSnpEffect.rows[0].slice(0,4),t=i.totalSnpEffect.rows[0][4].split(";"),s=t.findIndex((e=>!e.includes(":"))),r=t.splice(s,1)[0];o.data.totalSnpEffect.snp=n[r];const a=[];for(const e of t){if(!e.includes(":"))throw"expected interaction";const[t,s]=e.split(":");a.push({term1:n[t],term2:n[s]})}o.data.totalSnpEffect.interactions=a,o.data.totalSnpEffect.lst=e,o.data.totalSnpEffect.label="Total SNP effect"}i.tests&&(o.data.tests=i.tests,o.data.tests.label="Statistical tests"),o.data.other=i.other,o.data.other.label="Other summary statistics";for(const t of 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l(e){if(!e.cohort)throw"ds.cohort missing";if(!e.cohort.db)throw"ds.cohort.db missing";if(!e.cohort.termdb)throw"ds.cohort.termdb missing";const t=e.cohort.db.file_fullpath||e.cohort.db.file;if(!t)throw"both file and file_fullpath missing";let n;try{console.log("Connecting",t),n=(0,o.sE)(t),console.log(`DB connected for ${e.label}: ${t}`)}catch(e){throw`Cannot connect db ${t}: ${e.message||e}`}e.cohort.db.connection=n;const s=c(n),l=["cohorts","sampleidmap","terms","ancestry","alltermsbyorder","termhtmldef","category2vcfsample","chronicevents","precomputed_chc_grade","precomputed_chc_child","precomputed_cuminc","precomputed_cox","subcohort_terms","subcohort_samples","survival","features","cohort_features","anno_integer","anno_float","anno_categorical","buildDate"];for(const e of l)s.has(e)||console.log(`${e} table missing!!!!!!!!!!!!!!!!!!!!`);if(!s.has("terms"))throw"terms table missing";if(!s.has("ancestry"))throw"ancestry table 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u.getcohortsamplecount=()=>o}if(s.has("category2vcfsample")){const e=n.prepare("SELECT * FROM category2vcfsample");let t;u.getcategory2vcfsample=()=>{if(t)return t;t=e.all();for(const e of t)e.q=JSON.parse(e.q),e.categories=JSON.parse(e.categories);return t}}if(s.has("alltermsbyorder")){const e=n.prepare("SELECT * FROM alltermsbyorder");let t;u.getAlltermsbyorder=()=>{if(t)return t;const n=e.all();t=[];for(const e of n){const n=u.termjsonByOneid(e.id);n&&t.push({group_name:e.group_name,term:n})}return t}}{const e=n.prepare("SELECT name, jsondata FROM terms WHERE id=?"),t=new Map;u.termjsonByOneid=n=>{if(t.has(n))return t.get(n);const s=e.get(n);if(s){const e=JSON.parse(s.jsondata);return e.id=n,e.name=s.name||e.name,t.set(n,e),e}}}{const e=n.prepare("select id from terms where parent_id=?"),t=new Map;u.termIsLeaf=n=>{if(t.has(n))return t.get(n);let s=!0;const r=e.get(n);return r&&r.id&&(s=!1),t.set(n,s),s}}{const e=n.prepare("SELECT id, name, jsondata, s.included_types, 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n&&(s=u.termjsonByOneid(n)),e.set(t,s),s}}}{const e=n.prepare("SELECT id, name, type, jsondata, s.included_types, s.child_types \n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=? \n\t\t\tWHERE id IN (SELECT id FROM terms WHERE parent_id=?)\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),t=new Map;u.getTermChildren=(n,s="")=>{const r=n+";;"+s;if(t.has(r))return t.get(r);const o=e.all([s,n]);let i;return o&&(i=o.map((e=>{const t=JSON.parse(e.jsondata);return t.id=e.id,t.name=e.name||t.name,t.included_types=e.included_types?e.included_types.split(","):[],t.child_types=e.child_types?e.child_types.split(","):[],t}))),t.set(r,i),i}}{const e=n.prepare("SELECT id, name, jsondata, s.included_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE name LIKE ?");u.findTermByName=(t,n=10,s="",r=null,o=null,a=null)=>{const l=e.all([s,"%"+t+"%"]);if(l){const e=a||{equals:[],startsWith:[],startsWord:[],includes:[]};for(const n of l){if(!n.jsondata)continue;const s=n.name.toLowerCase(),r=JSON.parse(n.jsondata);r.id=n.id,r.name=n.name||r.name,r.included_types=n.included_types?n.included_types.split(","):[],o&&!(0,i.CG)(r,o).has("plot")||(s===t?e.equals.push(r):s.startsWith(t)?e.startsWith.push(r):s.includes(" "+t)?e.startsWord.push(r):e.includes.push(r))}return[...e.equals,...e.startsWith,...e.startsWord,...e.includes].slice(0,n)}}}{const e=n.prepare("SELECT MAX(value) AS v FROM anno_integer WHERE term_id=?"),t=n.prepare("SELECT MAX(value) AS v FROM anno_float WHERE term_id=?"),s=new Map;u.findTermMaxvalue=(n,r)=>{if(s.has(n))return s.get(n);const o=(r?e:t).get(n);return o?(s.set(n,o.v),o.v):void 0}}{const e={float:n.prepare("SELECT sample,value FROM anno_float WHERE term_id=?"),integer:n.prepare("SELECT sample,value FROM anno_integer WHERE term_id=?"),categorical:n.prepare("SELECT sample,value FROM anno_categorical WHERE term_id=?")};u.getAllValues4term=t=>{const n=u.termjsonByOneid(t);if(!n)return;const s=e[n.type];if(!s)return;const r=s.all(t);if(!r||0==r.length)return;const o=new Map;for(const e of r)o.set(e.sample,e.value);return o}}{const e=n.prepare("SELECT ancestor_id FROM ancestry WHERE term_id=?"),t=new Map;u.getAncestorIDs=n=>{if(t.has(n))return t.get(n);const s=e.all(n).map((e=>e.ancestor_id));return t.set(n,s),s}}{const e=n.prepare("SELECT t.name FROM ancestry as a, terms as t WHERE a.term_id=? AND t.id=a.ancestor_id"),t=new Map;u.getAncestorNames=n=>{if(t.has(n))return t.get(n);const s=e.all(n).map((e=>e.name));return t.set(n,s),s}}{const e={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=?")},t={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=? AND sample=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=? AND sample=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=? AND sample=?")},s={categorical:n.prepare("SELECT value FROM anno_categorical a,sampleidmap s WHERE term_id=? AND s.name=?"),integer:n.prepare("SELECT value FROM anno_integer a,sampleidmap s WHERE term_id=? AND s.name=?"),float:n.prepare("SELECT value FROM anno_float a, sampleidmap s WHERE term_id=? AND s.name=?")};u.getSample2value=(n,r=null)=>{const o=u.termjsonByOneid(n);return r?"string"==typeof r?s[o.type].all(n,r):t[o.type].all(n,r):e[o.type].all(n)}}if(s.has("termhtmldef")){const e=n.prepare("SELECT jsonhtml FROM termhtmldef WHERE id=?"),t=new Map;u.getTermInfo=n=>{if(t.has(n))return t.get(n);const s=e.get(n);if(s){const e=JSON.parse(s.jsonhtml);return e.id=n,t.set(n,e),e}}}u.getSupportedChartTypes=t=>{f(e);r().dsCredentials?.[e.label];const n={},s={};for(const o of e.cohort.termdb.termtypeByCohort)if(o.type){if(!(o.cohort in n)){n[o.cohort]=new Set(["regression","summary"]),e.cohort.scatterplots&&n[o.cohort].add("sampleScatter"),s[o.cohort]=0,e.cohort.allowedChartTypes?.includes("matrix")&&n[o.cohort].add("matrix");const r=a.i.getForbiddenRoutesForDsEmbedder(e.label,t);r.includes("termdb")||r.includes("*")||(n[o.cohort].add("dataDownload"),n[o.cohort].add("sampleView"),e.queries?.singleCell&&n[o.cohort].add("singleCellPlot"))}r().features?.draftChartTypes&&n[o.cohort].add(...r().features.draftChartTypes),"survival"!=o.type||n[o.cohort].has("survival")||n[o.cohort].add("survival"),"condition"!=o.type||n[o.cohort].has("cuminc")||n[o.cohort].add("cuminc"),"float"!=o.type&&"integer"!=o.type||(s[o.cohort]+=o.samplecount)}for(const e in s)s[e]>1&&n[e].add("sampleScatter");for(const e in n)n[e]=[...n[e]];if(e.cohort.allowedChartTypes)for(const t in n)n[t]=n[t].filter((t=>e.cohort.allowedChartTypes.includes(t)));if(e.queries){if(e.queries.snvindel||e.queries.trackLst)for(const e in n)n[e].push("genomeBrowser");if(e.queries.geneExpression)for(const e in n)n[e].push("hierCluster");if(e.queries.rnaseqGeneCount)for(const e in n)n[e].push("DEanalysis")}return n},u.getSingleSampleData=function(e,t=[]){const s=t.length?`and term_id in (${t.map((e=>"?")).join(",")})`:"",r=`select term_id, value, jsondata from ( select term_id, value \n\t\tfrom anno_categorical \n\t\twhere sample=? ${s}\n\t\tunion all \n\t\tselect term_id, \n\t\tvalue from anno_float \n\t\twhere sample=? ${s}\n\t\tunion all  \n\t\tselect term_id, value \n\t\tfrom anno_integer \n\t\twhere sample=? ${s}\n\t\tunion all \n\t\tselect term_id, (min_years_to_event || ' ' || value) as value \n\t\tfrom precomputed_chc_grade \n\t\twhere max_grade=1 and sample=? ${s}\n\t\tunion all \n\t\tselect term_id, (tte || ' ' || exit_code) as value \n\t\tfrom survival \n\t\twhere sample=? ${s}) join terms on terms.id = term_id`;return n.prepare(r).all([e,...t,e,...t,e,...t,e,...t,e,...t])},u.getProfileFacilities=function(){return n.prepare("select name from sampleidmap join \n\t\tanno_categorical on sampleidmap.id = anno_categorical.sample\n\t\twhere term_id = 'sampleType' and value = 'Facility'").all()}}function c(e){const t=e.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(t.map((e=>e.name)))}function f(e){if(e.cohort.termdb.termtypeByCohort){if(!Array.isArray(e.cohort.termdb.termtypeByCohort))throw"termtypeByCohort is not array"}else{if(!e.cohort?.db?.connection)throw"termtypeByCohort[] not set but cohort.db.connection missing";e.cohort.termdb.termtypeByCohort=e.cohort.db.connection.prepare("WITH c AS (\n\t\t\tSELECT cohort, term_id\n\t\t\tFROM subcohort_terms s\n\t\t\tGROUP BY cohort, term_id\n\t\t) \n\t\tSELECT cohort, type, count(*) as samplecount\n\t\tFROM terms t\n\t\tJOIN c ON c.term_id = t.id\n\t\tGROUP BY cohort, type").all()}}},3795:(e,t,n)=>{"use strict";n.d(t,{G:()=>g,u:()=>y});var s=n(7147),r=n.n(s),o=n(1017),i=n.n(o),a=n(3345),l=n(8907),c=(n(2826),n(4521),n(334)),f=n.n(c),u=n(3625);const d="%CHROM\t%POS\t%REF\t%ALT[\t%TGT]\n",p="%POS\t%ID\t%REF\t%ALT\t%INFO[\t%TGT]\n",m="./.",h=1e3;async function g(e,t,n,s){try{if(e.sumSamples)return await async 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i)l.push({allele:e,count:i[e],isRef:e==s});d.push({snpid:n,alleles:l,gt2count:a})}return{numOfSampleWithAnyValidGT:u.size,snps:d}}(e,0,n);if(e.snptext)return await async function(e,t,n){if(!n.snp)throw"snp not supported by genome";if(!e.snptext)throw".snptext missing";const s=function(e){const t=[];for(const n of e.trim().split("\n")){const[e,s]=n.trim().split(/[\s\t]/);if(e&&e.startsWith("rs")){if(t.find((t=>t.rsid==e)))continue;const n={rsid:e,snpid:e};s&&(n.effectAllele=s),t.push(n)}else t.push({rsid:e,snpid:e,invalid:"INVALID RSID"})}return t}(e.snptext);if(!s.length)throw"no snps";await async function(e,t){for(const n of e)if(!n.invalid)if(n.chr&&"string"==typeof n.chr){const e=t.chrlookup[n.chr.toUpperCase()];if(!e){n.invalid=!0;continue}if(!Number.isInteger(n.pos)){n.invalid=!0;continue}if(n.pos<=0||n.pos>=e.len){n.invalid=!0;continue}}else if(n.rsid){const e=await a.mr(t.snp.bigbedfile,n.rsid),s=[];for(const n of e){const e=n.split("\t"),r=t.chrlookup[e[0].toUpperCase()];r&&r.major&&s.push(e)}if(0==s.length){n.invalid=!0;continue}const r=s[0];n.chr=r[0],n.pos=Number.parseInt(r[1]),n.dbsnpRef=r[4],n.dbsnpAlts=r[6].split(",").filter(Boolean)}else n.invalid=!0;if(!e.find((e=>!e.invalid)))throw"no valid variants"}(s,n);const o=await async function(e,t,n){let s;if(n.track){if(s=n.track.vcf,!s)throw"ds.track.vcf missing"}else s=n.queries.snvindel.byrange._tk;const o=new Set,l=[];for(const e of t){if(e.invalid)continue;let t;if(s.chr2files){if(t=s.chr2files?.[e.chr].file,!t)throw"chr not in chr2files"}else if(s.chr2bcffile){if(t=s.chr2bcffile[e.chr],!t)throw"chr not in chr2bcffile"}else t=s.file||s.url;o.add(t);const n=(s.nochr?e.chr.replace("chr",""):e.chr)+"\t"+(e.pos+1);l.push(n)}const c=i().join(f().cachedir,await a.tG(l.join("\n"))),u=i().join(f().cachedir,await a.tG([...o].join("\n")));await a.UE({isbcf:!0,args:["query","-R",c,"-f",d,"-v",u],dir:s.dir,callback:e=>{const n=e.split("\t"),r=(s.nochr?"chr":"")+n[0],o=n[1],i=n[2],a=n[3].split(","),l=t.find((e=>{if(e.chr==r&&e.pos===o-1&&e.dbsnpRef==i&&e.dbsnpAlts.some((e=>a.includes(e))))return e}));if(l){l.referenceAllele=i,l.altAlleles=a,l.gtlst=[];for(let e=4;e<n.length;e++)l.gtlst.push(n[e]==m?"":n[e])}}}),r().unlink(c,(()=>{})),r().unlink(u,(()=>{}));const p=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((e=>e.name)).join("\t")];for(const e of t)e.invalid||e.gtlst&&(p.push(e.snpid+"\t"+e.chr+"\t"+e.pos+"\t"+e.referenceAllele+"\t"+e.altAlleles.join(",")+"\t"+(e.effectAllele||"")+"\t"+e.gtlst.join("\t")),delete e.gtlst);const h=e.genome+"_"+e.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random());return await a.Sf(i().join(f().cache_snpgt.dir,h),p.join("\n")),h}(e,s,t);return{snps:s,cacheid:o}}(e,n,s);if(e.chr)return await async function(e,t,n){const s=Number(e.start),r=Number(e.stop);if(!Number.isInteger(s)||!Number.isInteger(r))throw"start/stop are not integers";if(s>r||s<0)throw"invalid start/stop coordinate";let o,l;if(t.track){if(o=t.track.vcf,!o)throw"ds.track.vcf missing";if(l=o.chr2bcffile[e.chr],!l)throw"chr not in chr2bcffile"}else if(o=t.queries.snvindel.byrange._tk,l=o.chr2files?o.chr2files?.[e.chr].file:o.file||o.url,!l)throw"no bcf file";const c=(o.nochr?e.chr.replace("chr",""):e.chr)+":"+s+"-"+r,d=["query",l,"-r",c,"-f",p];e.variant_filter&&y(e.variant_filter,d);const g={snps:[]},b=["snpid\tchr\tpos\tref\talt\teff\t"+o.samples.map((e=>e.name)).join("\t")];return await a.UE({isbcf:!0,args:d,dir:o.dir,callback:(t,n)=>{if(g.snps.length>=h)return n.kill(),void(g.reachedVariantLimit=!0);const s=t.split("\t"),r=Number(s[0])-1,i=s[1],a=s[2],l=s[3].split(","),c=i&&"."!=i?i:r+"."+a+"."+l.join(","),f={snpid:c,chr:e.chr,pos:r};(0,u.H)(o,a,l,f,s[4],s[1]);for(const e of f.mlst)e.vcf_id&&(e.mname=e.vcf_id);g.snps.push(f);const d=[c,e.chr,r,a,l.join(","),""];for(let e=5;e<s.length;e++)d.push(s[e]==m?"":s[e]);b.push(d.join("\t"))}}),g.cacheid=e.genome+"_"+e.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random()),await a.Sf(i().join(f().cache_snpgt.dir,g.cacheid),b.join("\n")),g}(e,n);throw"unknown how to validate"}catch(e){return e.stack&&console.log(e.stack),{error:e.message||e}}}function y(e,t){const n=[];for(const t of e.lst)if(t.tvs.values){const e=t.tvs.isnot?"!=":"=";for(const s of t.tvs.values){const r=isNaN(s.key)?`"${s.key}"`:Number(s.key);n.push(`INFO/${t.tvs.term.id}${e}${r}`)}}else{if(!t.tvs.ranges)throw`unknown tvs spec for info_field: type=${t.type}, term.id=${t.tvs.term.id}`;for(const e of t.tvs.ranges)"start"in e&&n.push(`INFO/${t.tvs.term.id} ${e.startinclusive?">=":">"} ${e.start}`),"stop"in e&&n.push(`INFO/${t.tvs.term.id} ${e.stopinclusive?"<=":"<"} ${e.stop}`)}0!=n.length&&t.push("-i",n.join(" && "))}},8907:(e,t,n)=>{"use strict";n.d(t,{yT:()=>C,YG:()=>T,g5:()=>S,J4:()=>N,B9:()=>q,cf:()=>k,tt:()=>x,Bi:()=>A,ig:()=>M});var s={};n.r(s),n.d(s,{binary:()=>u,continuous:()=>l,cubicSpline:()=>c,discrete:()=>f});var r={};n.r(r),n.d(r,{groupset:()=>m,values:()=>d});var o={};n.r(o),n.d(o,{binary:()=>g,cox:()=>b,cuminc:()=>y,discrete:()=>h});var i=n(4048),a=n(5257);const l={getCTE(e,t,n,s,r,o,i){r.push(t.id);const a=C(t,s);return r.push(...a.values),{sql:`${e} AS (\n\t\t\t\tSELECT \n\t\t\t\t\tsample,\n\t\t\t\t\tvalue as key, \n\t\t\t\t\tvalue\n\t\t\t\tFROM anno_${t.type}\n\t\t\t\tWHERE term_id=? ${a.clause}\n\t\t\t)`,tablename:e}}},c=l,f={getCTE(e,t,n,s,r,o,i){r.push(t.id);const a=T(s,t,n,o,i),l=[],c=new Map;s.bin_size;for(const e of a)!("name"in e)&&e.label&&(e.name=e.label),c.set(e.name,e),l.push(`SELECT '${e.name}' AS name,\n\t\t\t\t${null==e.start?0:e.start} AS start,\n\t\t\t\t${null==e.stop?0:e.stop} AS stop,\n\t\t\t\t0 AS unannotated,\n\t\t\t\t${e.startunbounded?1:0} AS startunbounded,\n\t\t\t\t${e.stopunbounded?1:0} AS stopunbounded,\n\t\t\t\t${e.startinclusive?1:0} AS 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("+f.join(",")+") AND":""}\n\t\t\t\t\t\t(\n\t\t\t\t\t\t\tb.startunbounded = 1\n\t\t\t\t\t\t\tOR value > b.start\n\t\t\t\t\t\t\tOR (b.startinclusive=1 AND value = b.start)\n\t\t\t\t\t\t)\n\t\t\t\t\t\tAND\n\t\t\t\t\t\t(\n\t\t\t\t\t\t\tb.stopunbounded\n\t\t\t\t\t\t\tOR value < b.stop\n\t\t\t\t\t\t\tOR (b.stopinclusive=1 AND value = b.stop)\n\t\t\t\t\t\t)\n\t\t\t\t\t)\n\t\t\t\tWHERE\n\t\t\t\tterm_id=? ${d.clause}\n\t\t\t)`,tablename:e,name2bin:c,bins:a}}},u=f,d={getCTE(e,t,n,s,r){r.push(t.id);const o=C(t,s);return r.push(...o.values),{sql:`${e} AS (\n\t\t\t\tSELECT sample,value as key, value as value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id=? ${o.clause}\n\t\t\t)`,tablename:e}}};let p=0;const m={async getCTE(e,t,n,s,r,o){if(!o.groups)throw`.groups[] missing from a group-set, term.id='${t.id}'`;const i=[],a=[];for(const e of o.groups)if("values"==e.type)i.push(`SELECT sample, ? as key, value\n\t\t\t\t\tFROM anno_categorical a\n\t\t\t\t\tWHERE term_id=?\n\t\t\t\t\t\tAND value IN (${e.values.map((e=>"?")).join(",")})\n\t\t\t\t`),r.push(e.name,t.id,...e.values.map((e=>e.key.toString())));else{if("filter"!=e.type)throw`unsupported groupset type='${e.type}'`;if(!("activeCohort"in s.groupsetting)||!e.filter4activeCohort)throw`activeCohort error: cannot construct filter statement for group name='${e.name}', term.id=${t.id}`;{const o=e.filter4activeCohort[s.groupsetting.activeCohort],l=await getFilterCTEs(o,n,"xf"+p++);if(!l)throw`unable to construct a group='${e.name}' filter for term.id='${t.id}'`;a.push(l.filters),r.push(...l.values.slice(),e.name,e.name),i.push(`SELECT sample, ? AS key, ? AS value\n\t\t\t\t\t\tFROM ${l.CTEname}`)}}return{sql:`${a.length?a.join("\n,")+",":""}\n\t\t\t${e} AS (\n\t\t\t\t${i.join("\nUNION ALL\n")}\n\t\t\t)`,tablename:e}}},h={getCTE(e,t,n,s,r){if(s.breaks&&s.breaks.length>0)return w(e,t,s,r);{const[n,o]=v(s);r.push(t.id);const i=C(t,s);return r.push(...i.values),{sql:`${e} AS (\n\t\t\t\t\tSELECT\n\t\t\t\t\t\tsample,\n\t\t\t\t\t\tvalue as key,\n\t\t\t\t\t\tvalue\n\t\t\t\t\tFROM\n\t\t\t\t\t\t${"grade"==n?"precomputed_chc_grade":"precomputed_chc_child"}\n\t\t\t\t\tWHERE\n\t\t\t\t\t\tterm_id = ?\n\t\t\t\t\t\tAND ${o} = 1\n\t\t\t\t\t\t${i.clause}\n\t\t\t\t)`,tablename:e}}}},g={getCTE(e,t,n,s,r){if(1!=s.breaks?.length)throw"binary mode requires one break";return w(e,t,s,r)}},y={getCTE(e,t,n,s,r){if(1!=s.breaks?.length)throw"cuminc mode requires one break";return r.push(t.id,s.breaks[0]),{sql:`${e} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tevent AS key,\n\t\t\t\t\ttime AS value\n\t\t\t\tFROM\n\t\t\t\t\tprecomputed_cuminc\n\t\t\t\tWHERE\n\t\t\t\t\tterm_id = ?\n\t\t\t\t\tAND grade_cutoff = ?\n\t\t\t)`,tablename:e}}},b={getCTE(e,t,n,s,r){if(1!=s.breaks?.length)throw"cox mode requires one break";r.push(t.id,s.breaks[0]);const o=Object.keys(t.values).map(Number),i=Math.max(...o);return{sql:`${e} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tevent AS key,\n\t\t\t\t\tjson_object('age_start', age_start, 'age_end', age_end) AS value\n\t\t\t\tFROM\n\t\t\t\t\tprecomputed_cox\n\t\t\t\tWHERE\n\t\t\t\t\tterm_id = ?\n\t\t\t\t\tAND grade_cutoff = ?\n\t\t\t)`,tablename:e,events:[{event:1,label:`Event (grade ${s.breaks[0]===i?s.breaks[0]:`${s.breaks[0]}-${i}`})`},{event:0,label:"Censored/death"},{event:-1,label:"Event before entry into the cohort"}]}}};function v(e){const t=e.bar_by_children?"child":e.bar_by_grade?"grade":"";if(!t)throw"must set the bar_by_grade or bar_by_children query parameter";const n=e.value_by_max_grade?"max_grade":e.value_by_most_recent?"most_recent":e.value_by_computable_grade?"computable_grade":"";if(!n)throw"must set a valid value_by_*";return[t,n]}function w(e,t,n,s){const[r,o]=v(n);if("grade"!=r)throw"breaks must be used on grade values";const i=[];for(const e of n.groups)i.push(`SELECT sample, ? as key, value\n\t\t\tFROM precomputed_chc_grade\n\t\t\tWHERE\n\t\t\t\tterm_id=?\n\t\t\t\tAND ${o}=1\n\t\t\t\tAND value IN (${e.values.map((e=>"?")).join(",")})\n\t\t`),s.push(e.name,t.id,...e.values.map((e=>e.toString())));return{sql:`${e} AS (\n\t\t\t${i.join("\nUNION ALL\n")}\n\t\t)`,tablename:e}}const _={getCTE(e,t,n){let s,r,o="";for(const[e,i]of t.q.groups.entries())"in"in i||(i.in=!0),s=i.values.map((e=>e.sampleId)),r=s.map((()=>"?")).join(","),o+=`SELECT id as sample, ? as key, ? as value\n\t\t\t\tFROM sampleidmap\n\t\t\t\tWHERE sample ${i.in?"":"NOT"} IN (${r})\n\t\t\t`,e!=t.q.groups.length-1&&(o+="UNION ALL "),n.push(i.name,i.name,...s);return{sql:`${e} AS (${o})`,tablename:e}}};n(334),n(3345);async function k(e,t,n=!1){const s=await(0,a.w)(e,t),r=t.cohort.db.connection.prepare(s?`WITH ${s.filters} SELECT sample as id, name FROM ${s.CTEname} join sampleidmap on sample = sampleidmap.id`:"SELECT id, name FROM sampleidmap");let o;if(o=s?r.all(s.values):r.all(),n)return o;for(const e of o)delete e.name;return o}async function q(e,t){if(!e.filter)throw"filter missing";let n;if("object"==typeof e.filter)n=e.filter;else{if("string"!=typeof e.filter)throw"q.filter not obj or str";n=JSON.parse(e.filter)}const s=await(0,a.w)(n,t),r=`WITH ${s.filters}\n\t\tSELECT 'FILTERED_COHORT' as subcohort, count(distinct sample) as samplecount \n\t\tFROM ${s.CTEname}`;return t.cohort.db.connection.prepare(r).all(s.values)}async function x(e){const t=e.ds.cohort.termdb.q.termjsonByOneid(e.term_id);if("integer"!=t.type&&"float"!=t.type)throw"term is not numeric";if(!t.values)return[];const n=await(0,a.w)(e.filter,e.ds),s=n?n.values.slice():[];s.push(e.term_id);const r=[];for(const e in t.values)r.push("?"),s.push(Number(e));const o=`\n\t\t${n?"WITH "+n.filters:""}\n\t\tSELECT count(sample) AS samplecount,value\n\t\tFROM anno_${t.type}\n\t\tWHERE term_id=?\n\t\t${n?"AND sample IN "+n.CTEname:""}\n\t\tAND value IN (${r.join(",")})\n\t\tGROUP BY value`;return e.ds.cohort.db.connection.prepare(o).all(s)}async function N(e){if(!e.key)throw".key missing";if(!e.ds)throw".ds{} missing";const t=await(0,a.w)(e.filter,e.ds),n=t?t.values.slice():[],s=e.ds.cohort.termdb.q.termjsonByOneid(e.key);n.push(e.key);const r=`\n\t\t${t?"WITH "+t.filters:""}\n\t\tSELECT sample, value\n\t\tFROM anno_${s.type}\n\t\tWHERE term_id=?\n\t\t${t?" 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