@sjcrh/proteinpaint-server 2.43.1 → 2.43.2

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Files changed (5) hide show
  1. package/package.json +1 -1
  2. package/routes/termdb.singlecellSamples.ts +10 -9
  3. package/server.js +1 -1
  4. package/server.js.map +1 -1
  5. package/src/serverconfig.js +9 -4
package/server.js CHANGED
@@ -1,2 +1,2 @@
1
- (()=>{var e={5037:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>c});var s=n(9157),r=n(1017),o=n.n(r),i=n(334),a=n.n(i),l=n(3345);const c={endpoint:"burden",methods:{get:{init:({genomes:e})=>async(t,n)=>{try{const r=e[t.query.genome];if(!r)throw`invalid q.genome=${t.query.genome}`;const i=t.query,c=r.datasets[i.dslabel];if(!c)throw`invalid q.genome=${t.query.dslabel}`;if(!c.cohort.cumburden?.files)throw"missing ds.cohort.cumburden.files";const f=await async function(e,t){const n=o().join(a().cachedir,Math.random().toString()+".json");for(const t in e.query)e.query[t]=Number(e.query[t]);const r=Object.assign({},u,e.query);await(0,l.Sf)(n,JSON.stringify(r));const{fit:i,surv:c,sample:f}=t.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}`],p=await(0,s.default)(o().join(a().binpath,"utils/burden.R"),[],d),m=JSON.parse(p[0]);return m}(t,c),{keys:d,rows:p}=function(e){const t=Object.keys(e[0]),n=[],s=[];for(const e of t)if("chc"==e)s.push(e),n.push(e);else{const t=Number(e.slice(1).split(",")[0]);t<=60&&t%2==0&&(s.push(e),n.push(`burden${t}`))}const r=[];for(const t of e)r.push(s.map((e=>t[e])));return{keys:n,rows:r}}(f);n.send({status:"ok",keys:d,rows:p})}catch(e){n.send({status:"error",error:e.message||e})}},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:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>f,maxTotalSizeCompressed:()=>u});var s=n(1017),r=n.n(s),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:e}){return async(t,n)=>{try{const s=e.hg38;if(!s)throw"hg38 missing";const o=s.datasets.GDC;if(!o)throw"hg38 GDC missing";const a=await async function(e,t){const n={op:"and",content:[{op:"=",content:{field:"data_format",value:"MAF"}},{op:"=",content:{field:"experimental_strategy",value:e.experimentalStrategy}},{op:"=",content:{field:"analysis.workflow_type",value:c}},{op:"=",content:{field:"access",value:"open"}}]},s={op:"and",content:[]};e.filter0&&s.content.push(e.filter0);const{host:o,headers:a}=t.getHostHeaders(e),d={filters:n,case_filters:s,size:l,fields:["id","file_size","cases.project.project_id","cases.submitter_id","cases.samples.sample_type"].join(",")},p=await i().post(r().join(o.rest,"files"),{headers:a,body:JSON.stringify(d)});let m;try{m=JSON.parse(p.body)}catch(e){throw"invalid JSON from "+f.endpoint}if(!Number.isInteger(m.data?.pagination?.total))throw"re.data.pagination.total is not int";if(!Array.isArray(m.data?.hits))throw"re.data.hits[] not array";const h=[];for(const e of m.data.hits){const t=e.cases?.[0];if(!t)throw"h.cases[0] missing";const n={id:e.id,project_id:t.project.project_id,file_size:e.file_size};n.case_submitter_id=t.submitter_id,t.samples&&(n.sample_types=t.samples.map((e=>e.sample_type)).sort()),h.push(n)}return{files:h,filesTotal:m.data.pagination.total,maxTotalSizeCompressed:u}}(t.query,o);n.send(a)}catch(e){n.send({status:"error",error:e.message||e})}}},request:{typeId:"GdcMafRequest"},response:{typeId:"GdcMafResponse"},examples:[{request:{body:{experimentalStrategy:"WXS",embedder:"localhost"}},response:{header:{status:200}}}]}}}},86:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>f});var s=n(6452),r=n.n(s),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:e}){return async(t,n)=>{try{const s=e.hg38;if(!s)throw"hg38 missing";const o=s.datasets.GDC;if(!o)throw"hg38 GDC missing";await async function(e,t,n){const s=Date.now(),{host:o,headers:l}=n.getHostHeaders(e),f=await async function(e,t,n){if(0==e.length)throw"fileIdLst[] not array or blank";const s={filters:{op:"in",content:{field:"file_id",value:e}},size:1e4,fields:"file_size"},o=await r().post(i().join(t.rest,"files"),{headers:n,body:JSON.stringify(s)});let a;try{a=JSON.parse(o.body)}catch(e){throw"invalid json from getFileLstUnderSizeLimit"}if(!Array.isArray(a.data?.hits))throw"re.data.hits[] not array";const l=[];let c=0;for(const e of a.data.hits){if(c>=u.maxTotalSizeCompressed)break;if(!e.id)throw".id missing";if(!Number.isInteger(e.file_size))throw".file_size not integer";c+=e.file_size,l.push(e.id)}if(0==l.length)throw"no file available";return l}(e.fileIdLst,o,l);c().debugmode&&console.log(`${f.length} out of ${e.fileIdLst.length} input MAF files accepted by size limit`,Date.now()-s);const d={fileIdLst:f,columns:e.columns,host:i().join(o.rest,"data")},p=(0,a.run_rust_stream)("gdcmaf",JSON.stringify(d));t.setHeader("Content-Type","application/octet-stream"),t.setHeader("Content-Disposition","attachment; filename=cohort.maf.gz"),p.pipe(t),p.on("end",(()=>{c().debugmode&&console.log("rust gdcmaf",Date.now()-s),t.end()})),p.on("error",(e=>{console.error(e),t.statusCode=500,t.end("Internal Server Error")}))}(t.query,n,o)}catch(e){e.stack&&console.log(e.stack),n.send({status:"error",error:e.message||e})}}},request:{typeId:"GdcMafBuildRequest"},response:{typeId:null}}}}},889:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>l});var s=n(2273),r=n(6452),o=n.n(r),i=n(334),a=n.n(i);const l={endpoint:"gdc/topMutatedGenes",methods:{all:{init:function({genomes:e}){return async(t,n)=>{const r=t.query,i=e.hg38;if(!i)throw"hg38 missing";const l=i.datasets.GDC;if(!l)throw"hg38 GDC missing";try{const e=await async function(e,t){let n,r;const{host:i,headers:l}=t.getHostHeaders(e);a().features?.geneExpHost?(n=c.query,r=c.getVariables(e)):(n=u.query,r=u.getVariables(e));const f=await o().post(i.graphql,{headers:l,body:JSON.stringify({query:n,variables:r})}),d=JSON.parse(f.body),p=[];for(const e of d.data.genesTableViewer.explore.genes.hits.edges){if("object"!=typeof e.node)throw"node missing from re.data.genesTableViewer.explore.genes.hits.edges[]";const t=[];Number.isInteger(e.node.case_cnv_gain?.hits?.total)&&e.node.case_cnv_gain.hits.total>0&&t.push({class:s.mclasscnvgain,count:e.node.case_cnv_gain.hits.total}),Number.isInteger(e.node.case_cnv_loss?.hits?.total)&&e.node.case_cnv_loss.hits.total>0&&t.push({class:s.mclasscnvloss,count:e.node.case_cnv_loss.hits.total}),Number.isInteger(e.node.ssm_case?.hits?.total)&&e.node.ssm_case.hits.total>0&&t.push({dt:s.dtsnvindel,count:e.node.ssm_case.hits.total}),p.push({gene:e.node.symbol,mutationStat:t})}return 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}},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: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:u,request:{typeId:"HicdataRequest"},response:{typeId:"HicdataResponse"}},post:{alternativeFor:"get",init:u}}};function u(){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 u=["log(oe)"==e.matrixType?"oe":e.matrixType?e.matrixType:"observed",e.nmeth||"NONE",a,e.pos1,e.pos2,e.isfrag?"FRAG":"BP",e.resolution],f=(0,r.spawn)(l().hicstraw,u),d=i().createInterface({input:f.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])})),f.stderr.on("data",(e=>m.push(e))),f.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:()=>u});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 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(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 u=Number(j());let f=[];const d=1e5;if(8==l||7==l){let t=await q(e,u,d);const n=t.getInt32(0,!0);n>0&&(t=await q(e,u+n+4,d),f=await x(t,u+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);f=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=f,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 f("string");r.push(e),8==l||7==l?(e=await f("string"),c(4),c(8*await f("int32")),c(12*await f("int32"))):9==l&&(i+=4,e=await f("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&&u(),i+=e}async function u(){t=await q(e,n+i,d),n+=i,i=0}async function f(e){let n;if("string"==e){let e,s="";for(;i<t.byteLength&&0!=(e=t.getUint8(i++));)i>d&&await u(),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 u(),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 u=c.buffer;return u.buffer.slice(u.byteOffset,u.byteOffset+u.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},u=await(0,r.Yu)(c,o,i);if(u.error)throw u.error;const f=[];if("geneVariant"==e.type){const t=u.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)f.push({dt:e,classes:t})}else{const t=new Map;for(const n in u.samples){const s=u.samples[n][e.tid];s&&("key"in s&&t.set(s.key,1+(t.get(s.key)||0)))}for(const[n,s]of t)f.push({samplecount:s,key:n,label:u.refs?.byTermId?.[e.tid]?.events?.find((e=>e.event===n)).label||l?.values?.[n]?.label||n})}const d=(0,s.Tt)(l,u.refs?.byTermId?.[e.tid]?.bins||[],u.refs?.byTermId?.[e.tid]?.events,e.term1_q);d.length&&f.sort(((e,t)=>d.indexOf(e.label)-d.indexOf(t.label)));t.send({lst:f,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),u=n.n(c),f=n(4555),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 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f=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 f){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);u().debugmode&&console.log("clustering done:",Date.now()-c,"ms");return{clustering:f,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(u().tpmasterdir)||(e.file=r().join(u().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,f.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 a=i.datasets[t.query.dslabel];if(!a)throw"invalid dataset name";await async function(e,t,n){const o=n.cohort.termdb.q.termjsonByOneid(e.tid);if(!o)throw"invalid termid";if("float"!=o.type&&"integer"!=o.type)throw"not numerical term";const i=e.getpercentile,a=[],l=[],c=await s.J4({ds:n,key:e.tid,filter:e.filter?"string"==typeof e.filter?JSON.parse(e.filter):e.filter:null});for(const{value:e}of c)o.values&&o.values[e]&&o.values[e].uncomputable||o.skip0forPercentile&&0==e||l.push(Number(e));for(const e of i){const t=(0,r.Z)(l,e);a.push(t)}t.send({values:a})}(o,n,a)}catch(e){n.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}}},7095:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>r});var s=n(2826);const 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:()=>f,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),u=n(4555);const f={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,u.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 o=i().join(c().tpmasterdir,n.folder,s.toString());try{await r().promises.stat(o)}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"}const l=await(0,a.b5)(o);return{mlst:JSON.parse(l)}}}}},5707:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>s});const s={endpoint:"termdb/singlecellData",methods:{get:{init:r,request:{typeId:"TermdbSinglecellDataRequest"},response:{typeId:"TermdbSinglecellDataResponse"}},post:{alternativeFor:"get",init:r}}};function r({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?.singleCell)throw"no singlecell data on this dataset";r=await n.queries.singleCell.data.get(s)}catch(e){e.stack&&console.log(e),r={status:e.status||400,error:e.message||e}}n.send(r)}}},7934:(e,t,n)=>{"use 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n=t.cohort.termdb.q.getAllValues4term(e.isSampleTerm);if(0==n.size)throw"no samples found that are identified by isSampleTerm";const s=[];for(const e of n.keys())s.push({sample:t.cohort.termdb.q.id2sampleName(e),sampleid:e});if(e.sampleColumns)for(const n of e.sampleColumns){const e=t.cohort.termdb.q.getAllValues4term(n.termid);for(const t of s)e.has(t.sampleid)&&(t[n.termid]=e.get(t.sampleid))}for(const e of s)delete e.sampleid;e.get=()=>({samples:s})}(n.samples,e)}if("gdcapi"==n.data.src)(0,u.r8)(e,t);else{if("native"!=n.data.src)throw"unknown singleCell.data.src";!function(e,t){const n=new Set;for(const t of e.plots){if(n.has(t.name))throw"duplicate plot.name";n.add(t.name)}const s=[];for(const n of e.termIds){const e=t.cohort.termdb.q.termjsonByOneid(n);if(!e)throw"invalid term id from queries.singleCell.data.termIds[]";s.push(e)}e.get=async t=>{try{const n={};for(const t of e.termIds)n[t]={};const o=[];for(const s of e.plots){const l=i().join(c().tpmasterdir,s.folder,t.sample+s.fileSuffix);try{await r().promises.stat(l)}catch(e){if("ENOENT"==e.code)continue;if("EACCES"==e.code)throw"cannot read file, permission denied";throw"failed to load sc data file"}const u=(await(0,a.b5)(l)).trim().split("\n"),f=[];for(let t=1;t<u.length;t++){const r=u[t].split("\t"),o=r[0],i=Number(r[s.coordsColumns.x]),a=Number(r[s.coordsColumns.y]),l=r[s.colorColumn?.index]||"";if(!o)throw"cell id missing";if(!Number.isFinite(i)||!Number.isFinite(a))throw"x/y not number";f.push({cellId:o,x:i,y:a,category:l});for(const t of e.termIds)n[t][o]=r[1]}o.push({name:s.name,cells:f,colorBy:s.colorColumn?.name,colorMap:s.colorMap})}return 0==o.length?{nodata:!0}:{plots:o,terms:s,tid2cellvalue:n}}catch(e){return e.stack&&console.log(e.stack),{error:e.message||e}}}}(n.data,e)}}}},605:(e,t,n)=>{"use strict";n.r(t),n.d(t,{api:()=>r});var s=n(2826);const 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"+e.sampletype):e.patient&&(e.sample=e.patient+" "+e.sampletype)}else e.patient?e.sample?e.sampletype=e.sample:e.sample=e.sampletype=e.patient:e.sample&&(e.sampletype=e.sample);if(e.origin){switch(e.origin.toLowerCase()){case"r":case"relapse":i=s.moriginrelapse,e.isrim2=!0;break;case"g":case"germline":i=s.morigingermline,e.isrim1=!0;break;case"gp":case"germline pathogenic":i=s.morigingermlinepathogenic,e.isrim1=!0;break;case"gnp":case"germline nonpathogenic":case"germline non-pathogenic":i=s.morigingermlinenonpathogenic,e.isrim1=!0;break;case"s":case"somatic":case"diagnosis":i=s.moriginsomatic}}if(e.origin=i,!e.sample&&!e.patient)return;const a="no patient/individual name";if(e.patient?(t.patient2st[e.patient]||(t.patient2st[e.patient]={}),t.patient2st[e.patient][e.sampletype]=e.sample):(t.patient2st[a]||(t.patient2st[a]={}),t.patient2st[a][e.sampletype]=e.sample),e.sample&&e.disease)if(e.sample in t.sample2disease){if(e.disease!=t.sample2disease[e.sample])return t.snv.badlines.push([n,'conflict of disease types for sample "'+e.sample+'": '+e.disease+", "+t.sample2disease[e.sample],r]),!0}else t.sample2disease[e.sample]=e.disease;return!1}},5494:(e,t,n)=>{"use strict";n.r(t),n.d(t,{parseheader:()=>o,parseline:()=>i});var s=n(2273),r=n(8064);function o(e,t){const n=e.toLowerCase().split("\t");if(n.length<=1)return"invalid file header for snv/indel";const s=(...e)=>{for(const t of e){const e=n.indexOf(t);if(-1!=e)return e}return-1};let r=s("annovar_gene","annovar_sj_gene","gene","genename","gene_symbol","hugo_symbol");return-1==r?"gene missing from header":(n[r]="gene",r=s("annovar_aachange","amino_acid_change","annovar_sj_aachange","aachange","protein_change","variant"),-1==r?"amino_acid_change missing from header":(n[r]="mname",r=s("annovar_class","class","mclass","variant_class","variant_classification","annovar_sj_class"),-1==r?"variant_class missing from header":(n[r]="class",r=s("chromosome","chr"),-1==r?"chromosome missing from 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e={dt:o?r.dtsv:r.dtfusionrna,class:o?r.mclasssv:r.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}}]},t=n.geneToUpper?a.gene2.toUpperCase():a.gene2;n.data[t]||(n.data[t]=[]),n.data[t].push(e)}}}else c.push([e,"missing position2",i])}function a(e){const t={};for(const n in e){if("pairlst"==n)continue;const s=e[n];"object"!=typeof s&&(t[n]=s)}if(e.pairlst){t.pairlst=[];for(const n of e.pairlst){const e={};for(const t in n)"a"!=t&&"b"!=t&&"interstitial"!=t&&(e[t]=n[t]);if(n.a){e.a={};for(const t in n.a){const s=n.a[t];"object"!=typeof s&&(e.a[t]=s)}}if(n.b){e.b={};for(const t in n.b){const s=n.b[t];"object"!=typeof s&&(e.b[t]=s)}}if(n.interstitial){e.interstitial={};for(const t in n.interstitial){const 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t=(n.geneToUpper,u.gene.toUpperCase());n.data[t]||(n.data[t]=[]),n.data[t].push(u)}}function a(e){const t=[];for(const n of e){const e={a:{},b:{}};for(const t in n)"a"!=t&&"b"!=t&&(e[t]=n[t]);for(const t in n.a)e.a[t]=n.a[t];for(const t in n.b)e.b[t]=n.b[t];t.push(e)}return t}},8235:(e,t,n)=>{"use strict";n.r(t),n.d(t,{parseheader:()=>o,parseline:()=>i});var s=n(2273),r=n(8064);function o(e,t){const n=e.toLowerCase().split("\t");if(n.length<=1)return"invalid header line for truncation";const s=(...e)=>{for(const t of e){const e=n.indexOf(t);if(-1!=e)return e}return-1};let r=s("gene");if(-1==r)return"gene missing from header";if(n[r]="gene",r=s("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==r)return"isoform missing from header";n[r]="isoform";let o=!1;if(r=s("rnaposition"),-1!=r&&(n[r]="rnaposition",o=!0),r=s("losstype"),-1==r)return"lossType missing from header";n[r]="losstype";let 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F="CNV_loss";q[F]={label:"Copy number loss",color:"#a1d76a",dt:m,desc:"Copy number loss",key:F};const $="CNV_loh";q[$]={label:"LOH",color:"#12EDFC",dt:m,desc:"Loss of heterozygosity",key:$};const D="snv";q[D]={label:"SNV",color:"#92a2d4",dt:f,desc:"Single nucleotide variation",key:D};const L="mnv";q[L]={label:"MNV",color:"#92a2d4",dt:f,desc:"Multiple nucleotide variation",key:L};const P="insertion";q[P]={label:"Sequence insertion",color:"#bd8e91",dt:f,desc:"Sequence insertion",key:P};const G="deletion";q[G]={label:"Sequence deletion",color:"#b5a174",dt:f,desc:"Sequence deletion",key:G};const U={[f]:q.M.color};function B(e={}){if(e.mclass)for(const t in e.mclass){q[t]||(q[t]={});for(const n in e.mclass[t])q[t][n]=e.mclass[t][n]}}const z=function(e){const t=e.toLowerCase().split(",");let n=1;return-1!=t.indexOf("transcript_ablation")?[y,N,n]:(n++,-1!=t.indexOf("splice_acceptor_variant")?[f,"L",n]:(n++,-1!=t.indexOf("splice_donor_variant")?[f,"L",n]:(n++,-1!=t.indexOf("stop_gained")?[f,"N",n]:(n++,-1!=t.indexOf("frameshift_variant")?[f,"F",n]:(n++,-1!=t.indexOf("stop_lost")?[f,"N",n]:(n++,-1!=t.indexOf("start_lost")?[f,"N",n]:(n++,-1!=t.indexOf("transcript_amplification")?[f,T,n]:(n++,-1!=t.indexOf("inframe_insertion")||-1!=t.indexOf("conservative_inframe_insertion")||-1!=t.indexOf("disruptive_inframe_insertion")?[f,"I",n]:(n++,-1!=t.indexOf("inframe_deletion")||-1!=t.indexOf("conservative_inframe_deletion")||-1!=t.indexOf("disruptive_inframe_deletion")?[f,"D",n]:(n++,-1!=t.indexOf("missense_variant")?[f,"M",n]:(n++,-1!=t.indexOf("protein_altering_variant")?[f,"N",n]:(n++,-1!=t.indexOf("splice_region_variant")?[f,"P",n]:(n++,-1!=t.indexOf("incomplete_terminal_codon_variant")?[f,"N",n]:(n++,-1!=t.indexOf("stop_retained_variant")?[f,"S",n]:(n++,-1!=t.indexOf("synonymous_variant")?[f,"S",n]:(n++,-1!=t.indexOf("coding_sequence_variant")?[f,T,n]:(n++,-1!=t.indexOf("mature_mirna_variant")?[f,"E",n]:(n++,-1!=t.indexOf("5_prime_utr_variant")?[f,j,n]:(n++,-1!=t.indexOf("3_prime_utr_variant")?[f,C,n]:(n++,-1!=t.indexOf("non_coding_transcript_exon_variant")?[f,"E",n]:(n++,-1!=t.indexOf("intron_variant")?[f,"Intron",n]:(n++,-1!=t.indexOf("nmd_transcript_variant")?[f,"S",n]:(n++,-1!=t.indexOf("non_coding_transcript_variant")?[f,"E",n]:(n++,-1!=t.indexOf("upstream_gene_variant")?[f,M,n]:(n++,-1!=t.indexOf("downstream_gene_variant")?[f,M,n]:(n++,-1!=t.indexOf("tfbs_ablation")?[f,M,n]:(n++,-1!=t.indexOf("tfbs_amplification")?[f,M,n]:(n++,-1!=t.indexOf("tf_binding_site_variant")?[f,M,n]:(n++,-1!=t.indexOf("regulatory_region_ablation")?[f,M,n]:(n++,-1!=t.indexOf("regulatory_region_amplification")?[f,M,n]:(n++,-1!=t.indexOf("feature_elongation")?[f,M,n]:(n++,-1!=t.indexOf("regulatory_region_variant")?[f,M,n]:(n++,-1!=t.indexOf("feature_truncation")?[f,M,n]:(n++,-1!=t.indexOf("intergenic_variant")?[f,M,n]:(n++,[f,T,n])))))))))))))))))))))))))))))))))))},J='<circle 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The proportion is indicated by lack of any arc.",legend:'<circle cx="7" cy="12" r="7" fill="#b1b1b1"></circle>'};const V="G";H[V]={label:"Germline",desc:"A constitutional variant found in a normal sample. The proportion is indicated by the span of the solid arc within the whole circle.",legend:J},H.germline=H[V],H.somatic=H[W];const Z="R";H[Z]={label:"Relapse",desc:"A somatic variant found only in a relapse sample. 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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+zt<o.width&&i<o.width&&o.x<i+zt?e.fillRect(i,n,r.len*o.ntwidth+zt,s.stackheight):i+r.len*o.ntwidth+zt<o.width&&o.x>=i?e.fillRect(o.x,n,r.len*o.ntwidth+zt+i-o.x,s.stackheight):i+r.len*o.ntwidth+zt>=o.width&&o.x<i?e.fillRect(i,n,o.width-i,s.stackheight):i+r.len*o.ntwidth+zt>=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 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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:ft)+'">'+e.seq[t.cidx+n]+"</td>"):c.push('<td style="background:'+(r.toUpperCase()==o.toUpperCase()?rt:ft)(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 u=0,f=0,d=[],p=[],m=0;for(const t of e.boxes)u=f,f+=t.len,"S"==t.opr&&(m=1,d.push(u),p.push(f));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 h().promises.stat(t);if(!c.isFile())continue;const u=c.mtimeMs;u<e?(await h().promises.unlink(t),a++,o+=c.size):(n.push({path:t,time:u,size:c.size}),s+=c.size)}if(n.sort(((e,t)=>t.time-e.time)),s>=jn){const e=Date.now()-Tn;for(const t of n){if(t.time>e)break;if(await h().promises.unlink(t.path),t.deleted=!0,a++,o+=t.size,s-=t.size,s<jn)break}}console.log(`deleted ${a} of ${i} cached bam files (${o} bytes deleted, ${s} remaining)`),Mn=void 0,On=0;const l=s&&n.find((e=>!e.deleted));if(l){In(Tn+Math.round(s>=jn?0:Math.max(0,l.time+Cn-Date.now())))}}catch(e){console.error("Error in mayDeleteCacheFiles(): "+e)}}async function Rn(e,t,n,s,o,i){In(Tn);const{host:a,headers:l}=tn(i.query.__genomes).getHostHeaders(i.query);l.compression=!1;const c=y().join(r().cachedir_bam,o),u=a.rest+"/slicing/view/"+s+"?region="+e+":"+t+"-"+n;try{const e=Math.round(Date.now()/1e3);if(await F.yE(c)){if(await tt(v().stream(u,{method:"GET",headers:l}),h().createWriteStream(c)),await F.yE(c))throw"BAM file slice is not found after downloading"}else await h().promises.utimes(c,e,e);const t=c+".bai";if(await F.yE(t)){if(await async function(e){await F.UE({isbam:!0,args:["index",e],callback:()=>{}})}(c),await F.yE(t))throw"index file is missing after indexing"}else await h().promises.utimes(t,e,e);const n=await h().promises.stat(c);return(0,$.bplen)(n.size,!0)}catch(e){throw e.stack&&console.log(e.stack),"Error with BAM slicing: "+(e.message||e)}}r().features?.bamCache&&In(Tn);const Fn="Unannotated";function $n(e){return e.file?e.file:e.file2?e.file2:e.url}function Dn(e,t,n,s){const r=[];for(const o of e.samples)if(Number.isFinite(o.readcount)&&(o.readcount=Math.floor(o.readcount),!(o.readcount<=0||t.readcountCutoff&&o.readcount<t.readcountCutoff))){if(s.samples&&n.cohort&&n.cohort.annotation){const e=s.samples[o.i];if(!e)continue;const r=n.cohort.annotation[e];if(o.anno=r,t.cohortOnlyAttr&&n.cohort&&n.cohort.annotation){if(!r)continue;let e=!1;for(const n in t.cohortOnlyAttr){const 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s=I().createInterface({input:h().createReadStream(e.file,{encoding:"utf8"})}),r=[];let o=!0;s.on("line",(t=>{if(o)return void(o=!1);const n=t.split("\t"),[i,a,l,c,u,f]=n[0].split(/[:,]/);if(i!=e.chr)return;const d=Number.parseInt(a),p=Number.parseInt(u);if(Number.isNaN(d)||Number.isNaN(p))return;const m=d-1,h=p-1;if(m>e.start&&m<e.stop||h>e.start&&h<e.stop){const e=Number.parseInt(n[1]),t=n[2];r.push({chr:i,start:m,stop:h,type:t,rawdata:[e]})}else m>e.stop&&s.close()})),s.on("close",(()=>{t(r)}))}))}const Un=new Set(["-1","0","1","2"]);function Bn(e,t){e[0];const n=Number(e[1]),s=(e[2],e[3].split(".")[0]),r=e[5];if("+"!=r&&"-"!=r)return{name:s};const o="+"==r,i=Number(e[6]),a=Number(e[7]);if(!Number.isInteger(i)||!Number.isInteger(a))return{name:s,strand:r};const l=[],c=[],u=[],f=[],d=[],p=e[15],m=e[17],h=e[20];if(!e[10].includes(",")||!e[11].includes(","))return{name:s,strand:r};const g=e[10].split(",");g.pop();const y=g.map(Number),b=e[11].split(",");b.pop();const 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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,u=0,f=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 e=i._mapping[is+"."+r];e&&("keyword"==e.type?(l.type="categorical",u++):"long"==e.type?(l.type="integer",f++):"double"==e.type?(l.type="float",d++):console.log("GDC !!! ERR !!! 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(us[t.id]){t.bins=us[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 {\n\t\t cases {\n\t\t\taggregations(case_filters: $caseFilters, filters: $filters) {\n\t\t\t\t${n.join("\n")}\n\t\t\t}\n\t\t }\n\t\t}\n\t }\n\t}`,o={caseFilters:{},filters:{},filters2:{op:"range",content:[{ranges:[{from:0,to:1}]}]}};let i=0,a=0;const{host:l,headers:c}=t.getHostHeaders(),{body:u}=await(0,F.fk)(l.graphql,{method:"POST",body:{query:r,variables:o}});if("object"!=typeof u.data?.viewer?.explore?.cases?.aggregations)throw"return not object: re.data.viewer.explore.cases.aggregations{}";for(const[t,n]of s){const s=e.get(n);if(!(t in u.data.viewer.explore.cases.aggregations)){console.log("GDC: no stats object returned for numeric term",n),s.bins=cs,a++;continue}const r=u.data.viewer.explore.cases.aggregations[t].stats;if("object"!=typeof r){console.log("GDC: aggregations[facet].stats{} is not object"),s.bins=cs,a++;continue}if(!Number.isFinite(r.Max)||!Number.isFinite(r.Min)){s.bins=cs,a++;continue}if(r.Max<=r.Min){s.bins=cs,a++;continue}const 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="+u,"integer="+f,"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,r=null,o=null)=>{(e=e.toLowerCase()).includes(" ")&&(e=e.replace(/\s/g,"_"));const i=[];for(const n of t.values())o&&!(0,os.CG)(n,o)||n.id.includes(e)&&i.push(JSON.parse(JSON.stringify(n)));return await s(i,r),i},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=[],u&&e.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),f&&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}}},us={"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 fs=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"))||(!!fs.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 integers";r.push("size="+t),r.push("from="+n)}const{host:o,headers:i}=e.getHostHeaders(),{body:a}=await(0,F.fk)(o.rest+"/cases?"+r.join("&"),{headers:i});if(!Array.isArray(a?.data?.hits))throw"re.data.hits[] not array";for(const t of a.data.hits){const n=t.id;if(!n)throw"h.id (case uuid) missing";e.__gdc.caseIds.add(n);const s=t.submitter_id;if(!s)throw"h.submitter_id missing";if(e.__gdc.caseid2submitter.set(n,s),e.__gdc.map2caseid.cache.set(s,n),Array.isArray(t.samples))for(const s of t.samples){const t=s.submitter_id;if(!t)throw"sample.submitter_id missing";if(e.__gdc.map2caseid.cache.set(t,n),Array.isArray(s.portions))for(const r of s.portions)if(Array.isArray(r.analytes))for(const s of r.analytes)if(Array.isArray(s.aliquots))for(const r of s.aliquots){const s=r.aliquot_id;if(!s)throw"aliquot.aliquot_id missing";e.__gdc.aliquot2submitter.cache.set(s,t),e.__gdc.map2caseid.cache.set(s,n)}}}return a.data?.pagination?.total}var 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,u,f,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,u=l.geneA||l.chrA,f=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,u=l.geneB||l.chrB,f=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,f,c,encodeURIComponent(u)].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:f,pairlstIdx:c,mname:u,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 ${e.label}`)}var s;n.get=async function(t){if(2!=t.samplelst?.groups?.length)throw".samplelst.groups.length!=2";if(t.samplelst.groups[0].values?.length<1)throw"samplelst.groups[0].values.length<1";if(t.samplelst.groups[1].values?.length<1)throw"samplelst.groups[1].values.length<1";const s=[];let o=0;for(const r of t.samplelst.groups[0].values){if(!Number.isInteger(r.sampleId))continue;const t=e.cohort.termdb.q.id2sampleName(r.sampleId);t&&(n.allSampleSet.has(t)?s.push(t):o+=1)}const i=[];let a=0;for(const s of t.samplelst.groups[1].values){if(!Number.isInteger(s.sampleId))continue;const t=e.cohort.termdb.q.id2sampleName(s.sampleId);t&&(n.allSampleSet.has(t)?i.push(t):a+=1)}const l=s.length,c=i.length;if(l<1)throw"sample size of group1 < 1";if(c<1)throw"sample size of group2 < 1";const u={case:s.map((e=>e)).join(","),control:i.map((e=>e)).join(","),input_file:n.file,output_path:y().join(r().binpath,"utils")},f=8;let d;if(s.length<=f&&i.length<=f||"edgeR"==t.method){const e=new Date,n=(await async function(e,t){return new Promise(((n,s)=>{y().join(r().Rscript,e);const o=(0,x.spawn)(r().Rscript,[e]),i=[],a=[];try{je.Readable.from(t).pipe(o.stdin)}catch(t){o.kill();let n=t;a.length&&(n+=`killed edgeR('${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(u)),new Date);console.log("Time taken to run 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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 Us(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 zs(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 zs(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],u=Number(o[2]),f=o[3],d=o[4].split(","),p=o[5],m={pos:u-1};(0,gs.H)(n._tk,f,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 Us(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 u=[];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,u.push({chr:e,chrLen:n,xStart:a*(c-n),xStop:a*c})}const f=(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+f(i);p.fillRect(70+a,c,1,1)})),m.on("close",(()=>{!function(){p.strokeStyle="black",p.beginPath();{const e=220-f(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:u})}))}));function g(e){p.fillStyle="black",p.font="12px Arial",p.textAlign="right";const t=o+f(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 zs(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 zs(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 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o=0==s?[{samples:n}]:t[s-1].blocks;r.blocks=qr(o,r.id,e)}}(e,t,n),function(e,t){for(const n of e){const e=t.terms.find((e=>e.id==n.id));n.name=e.name;for(const t of n.blocks)t.samplecount=t.samples.length,delete t.samples,t.value&&(t.color=e.values[t.value].color)}}(t,e),function(e){for(let t=e.length-1;t>=0;t--){const n=e[t];for(const e of n.blocks){let t=0;for(const n of e.children)t+=n.symbolwidth;const n=e.isgap?1:e.samplecount.toString().length;e.symbolwidth=Math.max(n,t)}}let t=0;for(const n of e[0].blocks){n.x=t;let e=t;for(const t of n.children)t.x=e,e+=t.symbolwidth;t+=n.symbolwidth}for(let t=1;t<e.length;t++)for(const n of e[t].blocks){let e=n.x;for(const t of n.children)t.x=e,e+=t.symbolwidth}for(const t of e)delete t.children}(t),t}function qr(e,t,n){const s=[];for(const r of e){const e=new Map,o=[];for(const s of r.samples){const r=n.sample2term.get(s);if(r){const n=r.get(t);null==n?o.push(s):(e.has(n)||e.set(n,[]),e.get(n).push(s))}else o.push(s)}const 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e.filter((e=>l.has(e.name)))}async function Sr(e,t,n,s){const o=n.samplerule.set,i=e.url?await F.d1(e.url,e.indexURL):null,a=new Set,l=new Set,c=new Set;return await F.UE({args:[e.file?y().join(r().tpmasterdir,e.file):e.url,(e.nochr?o.chr.replace("chr",""):o.chr)+":"+o.start+"-"+(o.stop+1)],dir:i,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),i=Number.parseInt(n[2]),u=JSON.parse(n[3]);if(t.has(u.sample)){if(u.dt==$.dtcnv){if(!o.cnv)return;if(o.cnv.focalsizelimit&&i-r>=o.cnv.focalsizelimit)return;if(o.cnv.valuecutoff&&Math.abs(u.value)<o.cnv.valuecutoff)return;return s?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==$.dtloh){if(!o.loh)return;if(o.loh.focalsizelimit&&i-r>=o.loh.focalsizelimit)return;if(o.loh.valuecutoff&&u.segmean<o.loh.valuecutoff)return;return c.add(u.sample),void o.samples_loh.add(u.sample)}if(u.dt==$.dtsv){if(!o.sv)return;return c.add(u.sample),void o.samples_sv.add(u.sample)}if(u.dt==$.dtfusionrna){if(!o.fusion)return;return c.add(u.sample),void o.samples_fusion.add(u.sample)}if(u.dt==$.dtitd){if(!o.itd)return;return c.add(u.sample),void o.samples_itd.add(u.sample)}}}}),s?[a,l]:c}async function Ar(e,t,n,s,o){const i=o.samplerule.set,a=t.url?await F.d1(t.url,t.indexURL):null;await F.UE({args:[t.file?y().join(r().tpmasterdir,t.file):t.url,(t.nochr?i.chr.replace("chr",""):i.chr)+":"+i.start+"-"+(i.stop+1)],dir:a,callback:r=>{if(t.type==$.mdsvcftype.vcf){const[o,a,l]=D.S(r,{nochr:t.nochr,samples:t.samples,info:e.info,format:t.format});for(const e of a)if(e.sampledata&&!(i.snvindel.ref&&(e.ref!=i.snvindel.ref||e.alt!=i.snvindel.alt)||i.snvindel.hiddenclass&&($.vcfcopymclass(e,{}),i.snvindel.hiddenclass[e.class])))for(const t of e.sampledata)n.has(t.sampleobj.name)&&(s.add(t.sampleobj.name),i.samples_snvindel.add(t.sampleobj.name))}}})}async function Cr(e,t,n){if(!n.queries)throw".queries{} missing from ds";let s;for(const e in n.queries)n.queries[e].isgenenumeric&&(s=n.queries[e]);if(!s)throw"no gene numeric query from ds";const o=s.url?await F.d1(s.url,s.indexURL):null,i=t.samplerule.set,a=new Map;await F.UE({args:[s.file?y().join(r().tpmasterdir,s.file):s.url,i.chr+":"+i.start+"-"+i.stop],dir:o,callback:e=>{const t=JSON.parse(e.split("\t")[3]);t.sample&&Number.isFinite(t.value)&&t.gene==i.gene&&a.set(t.sample,t.value)}});const l=[];for(const t of e)a.has(t.name)&&(t.genevalue=a.get(t.name),l.push(t));return l.sort(((e,t)=>e.genevalue-t.genevalue)),[s,l]}function jr(e){e.lst.sort(((e,t)=>e.serialtime-t.serialtime));let t=e.lst.length,n=[],s=0;e.steps=[];for(const r of e.lst){if(0==r.censored){n.push(r.serialtime);continue}const o=1*(1-s)/(t-n.length);e.steps.push({x:r.serialtime,y:s,drop:o,censored:n}),s+=o,t-=n.length+1,n=[]}n.length>0&&e.steps.push({x:e.lst[e.lst.length-1].serialtime,y:s,drop:0,censored:n})}exports.do_plot=jr;const Tr={};function Mr(e,t,n){const s=+new Date;if(e.ip in Tr||(Tr[e.ip]={time:s,count:0}),s-Tr[e.ip].time>3e4)delete Tr[e.ip];else{if(Tr[e.ip].count>10)return void t.send({error:"busy"});Tr[e.ip].count++}throw t.send({error:n}),new Date+" "+n}const Or={genome(e){if("string"!=typeof e)throw"genome should be a non-empty string";if(/\s+/.test(e))throw"invalid genome character";return e},chr(e){if("string"!=typeof e)throw"chr should be a string";if(/\s+/.test(e))throw"invalid chr character";return e},start:e=>Number(e),term(e){const t="string"==typeof e?JSON.parse(e):e;if(!("id"in t))throw"missing termWrapper.id";if(!("q"in t))throw"missing termWrapper.q";return t}},Ir=require("cookie-parser");var Er=n.n(Ir),Rr=n(2062);function Fr(e){return!isNaN(parseFloat(e))&&isFinite(e)&&""!==e}var $r=n(5708);const Dr=e=>e.startsWith("[E::idx_test_and_fetch]"),Lr=(new Map,Object.freeze(r().features||{})),Pr={},Gr=r().tabix,Ur=r().samtools,Br=r().bcftools,zr=(r().bigwigsummary,r().hicstraw,"Unannotated"),Jr=i()();Jr.disable("x-powered-by"),r().users&&Jr.use(ve()({users:r().users,challenge:!0}));const Hr=r().basepath||"";function Wr(e){e.header("Vary","Origin"),e.header("Access-Control-Allow-Origin","*"),e.header("Access-Control-Allow-Methods","GET, POST, DELETE, OPTIONS, HEAD"),e.header("Access-Control-Allow-Headers","Origin, X-Requested-With, Content-Type, Accept, Authorization, origin, x-requested-with, content-type, accept, authorization, X-Auth-Token, X-Ds-Access-Token, X-SjPPDs-Sessionid, x-auth-token, x-ds-access-token, x-sjppds-sessionid")}if(!r().backend_only){const e=i().static(y().join(process.cwd(),"./public"),{setHeaders:Wr});Jr.use(e)}function Vr(e){const t={};for(const n in e.query)"jwt"!=n&&(t[n]=e.query[n]);console.log("%s\t%s\t%s\t%s",c().parse(e.url).pathname,new Date,e.header("x-forwarded-for")||e.connection.remoteAddress,JSON.stringify(t).replace(/\\"/g,'"'))}async function Zr(){try{if(r().preListenScript){const{cmd:e,args:t}=r().preListenScript,n=N().spawnSync(e,t,{encoding:"utf-8"});if(n.stderr.trim())throw n.stderr.trim();console.log(n.stdout)}r().appEnable&&r().appEnable.forEach((e=>Jr.enable(e)));const e=r().port,t=`STANDBY AT PORT ${e}`;if(r().ssl){const n={key:h().readFileSync(r().ssl.key),cert:h().readFileSync(r().ssl.cert)},s=await p().createServer(n,Jr);return s.listen(e,"0.0.0.0",(()=>{console.log(`HTTPS ${t}`)})),s}{const n=await f().createServer(Jr);return n.listen(e,"0.0.0.0",(()=>{process.send&&process.send("ready"),console.log(t)})),n}}catch(e){throw e}}function Kr(e){const 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]&&$.basecolor[e.alt]&&e.sampledata&&l.push(e)}return l}(o,t,n,s),l=[];for(const e in o.checkrnabam.samples){const n=o.checkrnabam.samples[e];n.hetsnps=[];for(const t of a){const s=ho(t,e,o.checkrnabam);s&&s.dnacount.ishet&&n.hetsnps.push(s)}if(n.url?n.dir=await 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t.sampledata)s.has(n.sampleobj.name)&&e.push(n);if(0==e.length)continue;t.sampledata=e}for(const e of t.sampledata)delete e.allele2readcount;delete t._m,delete t.vcf_ID,delete t.name,t.dt=$.dtsnvindel,l.push(t)}}else console.error("type not one of mdsvcftype: "+t.type)}));const u=[];c.stderr.on("data",(e=>u.push(e))),c.on("close",(e=>{const t=u.join("");!t||Dr(t)?i(l):a(t)}))}))));o.push(i)}return[null,Promise.all(o).then((t=>{const n=[];for(const e of t)for(const t of e)n.push(t);return{id:e.id,items:n}}))]}function jo(e){if(!e.endsWith(".gz"))return["no .gz suffix (file should be compressed by bgzip)"];const t=y().join(r().tpmasterdir,e);return h().existsSync(t)?h().existsSync(t+".tbi")||h().existsSync(t+".csi")?[null,t]:[".tbi/.csi index missing"]:[".gz file not found"]}Jr.use(q()()),Jr.use(((e,t,n)=>{"POST"==e.method.toUpperCase()&&(e.headers["content-type"]="application/json");try{e.query.encoding;!function(e){const t=e.encoding;for(const[n,s]of 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s={};e.body&&"POST"==e.method&&(s=e.body);const o=s.jwt?s.jwt:e.headers&&e.headers.authorization&&e.headers.authorization.startsWith("Bearer ")?e.headers.authorization.split(" ")[1]:null;if(!o)return t.send({error:"json web token missing"});R().verify(o,r().jwt.secret,((e,s)=>e?t.send({error:"Invalid token"}):s[r().jwt.permissioncheck]?void n():t.send({error:"Not authorized"})))}))),function(){if(!r().routeSetters)return;for(const e of r().routeSetters)if(e.endsWith(".js")){require(e)(Jr,Hr)}}(),mr.i.maySetAuthRoutes(Jr,Hr,r()),Jr.get(Hr+"/cardsjson",(async function(e,t){try{if(e.query.datafile&&e.query.tabixCoord)return new Promise(((n,s)=>{const o=(0,x.spawn)(Gr,[y().join(r().tpmasterdir,e.query.datafile),e.query.tabixCoord]),i=[],a=[];o.stdout.on("data",(e=>i.push(e))),o.stderr.on("data",(e=>a.push(e))),o.on("close",(e=>{""!=a.join("").trim()&&s("error querying bedj file");const 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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 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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 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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=[],u=[],f=[];if(e.alleleAlreadyUpdated)o=e.leftflankseqs,i=e.rightflankseqs,u=e.refseqs,f=e.altseqs,a=e.refalleles,l=e.altalleles,c=e.ref_positions,0!=u[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="",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(e.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 t=(await F.Kf(e.genome,o.chr+":"+o.pos+"-"+o.pos)).split("\n").slice(1).join("").toUpperCase();i=t+o.ref,u=t,o.pos-=1}else u=o.alt,i=o.ref;const f=o.pos,d=i.toUpperCase(),p=u.toUpperCase();0==r?(t=f-s,n=f+i.length+1+s):(f-s<t&&(t=f-s),f+i.length+1+s>n&&(n=f+i.length+1+s)),a.push(d),l.push(p),c.push(f),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),u.push(m),f.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:u[e],altseq:f[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:u,altseqs:f,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 u=[];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,u.push(t))}return{groups:u}}(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=fn(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=fn(e,s);r=mn(s,e,r),await pn(s,e,r),await un(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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function(e){const{gdc_id:t,filter0:n}=e,s={file_metadata:[],isCaseSample:"",numFilesSkippedByWorkflow:0},r=await Ze(t,s,n,e);if(!r.data.hits.length){if(s.isCaseSample)throw`No bam files available for this ${s.isCaseSample}.`;if(n){if((await Ze(t,s,null,e)).data.hits.length)throw"Case not in current cohort.";throw"Invalid input ID."}throw"Invalid input ID."}for(const e of r.data.hits){if(e.analysis.workflow_type==Je){s.numFilesSkippedByWorkflow++;continue}const t={};t.file_uuid=e.id,t.file_size=Ge(e.file_size),t.experimental_strategy=e.experimental_strategy,t.entity_id=e.associated_entities[0].entity_submitter_id,t.case_id=e.associated_entities[0].case_id,t.sample_type=e.cases[0].samples[0].sample_type,s.file_metadata.push(t)}return s}(t.query);await async function(e,t,n){if(!e.file_metadata?.length)return;const s=t.cookies.sessionid;if(!s)return;try{await Qe(e.file_metadata[0].file_uuid,n,t.query)}catch(t){"Permission denied"==t&&(e.userHasNoAccess=!0)}}(e,t,r),n.send(e)}else{const 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t={},n=e.split(" ").filter((function(e){return""!=e}))[0].split("\t");t.query_match=n[0],t.query_startpos=(parseInt(n[11])+1).toString(),t.query_stoppos=n[12],t.query_strand=n[8],t.query_totallen=n[10],t.query_alignlen=Math.abs(parseInt(n[11])-parseInt(n[12])).toString(),t.ref_chr=n[13],t.ref_startpos=(parseInt(n[15])+1).toString(),t.ref_stoppos=n[16],t.ref_alignlen=Math.abs(n[16]-n[15]).toString(),t.ref_totallen=n[14],c.push(t)}return c.sort(((e,t)=>t.query_match-e.query_match)),{hits:c}}(s,t.query.seq,t.query.soft_starts,t.query.soft_stops))}catch(e){n.send({error:e.message||e}),e.stack&&console.log(e.stack)}}}(Pr)),Jr.all(Hr+"/mds3",function(e){return async(t,n)=>{try{if(!t.query.genome)throw".genome missing";const s=e[t.query.genome];if(!s)throw"invalid genome";const r=function(e,t){const n=e.query;e.get("X-Auth-Token")&&(n.token=e.get("X-Auth-Token"));(0,F.Y5)(n,e.cookies),n.hiddenmclasslst&&(n.hiddenmclass=new Set(n.hiddenmclasslst.split(",")),delete n.hiddenmclasslst);return n}(t),o=await async function(e,t){if(e.dslabel){if(!t.datasets)throw".datasets{} missing from genome";const n=t.datasets[e.dslabel];if(!n)throw"invalid dslabel";return n}const n={queries:{}};if(e.bcffile||e.bcfurl){const[s,r,o]=(0,F.ZX)({query:{file:e.bcffile,url:e.bcfurl}});if(s)throw s;const i={};o?(i.url=r,i.indexURL=e.bcfindexURL):i.file=r,n.queries.snvindel={byrange:{_tk:i}},n.queries.snvindel.byrange.get=await Fs(n,t)}return n}(r,s);!function(e,t){if(e.filter0){const n="object"==typeof e.filter0?e.filter0:JSON.parse("string"==typeof e.filter0&&e.filter0.startsWith("%")?decodeURIComponent(e.filter0):e.filter0);e.filter0=t.validate_filter0(n)}e.filterObj&&"string"==typeof e.filterObj&&(e.filterObj=JSON.parse("string"==typeof e.filterObj&&e.filterObj.startsWith("%")?decodeURIComponent(e.filterObj):e.filterObj));if(e.skewerRim){if("format"!=e.skewerRim.type)throw"unknown skewerRim.type";if(!e.skewerRim.formatKey)throw"skewerRim.formatKey missing when 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function(e,t){if(e.singleSampleGenomeQuantification){if(!t.queries.singleSampleGenomeQuantification)throw"not supported on this dataset";const n=t.queries.singleSampleGenomeQuantification[e.singleSampleGenomeQuantification.dataType];if(!n)throw"invalid dataType";return await n.get(e.singleSampleGenomeQuantification.sample,e.devicePixelRatio)}if(e.singleSampleGbtk){if(!t.queries.singleSampleGbtk)throw"not supported on this dataset";const n=t.queries.singleSampleGbtk[e.singleSampleGbtk.dataType];if(!n)throw"invalid dataType";return await n.get(e.singleSampleGbtk.sample)}if(e.ssm2canonicalisoform){if(!t.ssm2canonicalisoform)throw"ssm2canonicalisoform not supported on this dataset";return{isoform:await t.ssm2canonicalisoform.get(e)}}if(e.variant2samples){if(!t.variant2samples)throw"not supported by server";return{variant2samples:await t.variant2samples.get(e)}}if(e.m2csq){if(t.queries&&t.queries.snvindel&&t.queries.snvindel.m2csq)return{csq:await t.queries.snvindel.m2csq.get(e)};throw"m2csq not supported on this dataset"}if(e.forTrack){const n={};if(e.skewer){if(n.skewer=[],t.queries.snvindel){const s=await async function(e,t){if(e.isoform&&t.queries.snvindel.byisoform)return await t.queries.snvindel.byisoform.get(e);if(e.rglst){if(!t.queries.snvindel.byrange)throw"q.rglst[] provided but .byrange{} is missing";return await t.queries.snvindel.byrange.get(e)}throw"insufficient query parameters for snvindel"}(e,t);n.skewer.push(...s)}if(t.queries.svfusion){const s=await async function(e,t){if(e.rglst){if(!t.queries.svfusion.byrange)throw"q.rglst provided but svfusion.byrange missing";return await t.queries.svfusion.byrange.get(e)}throw"insufficient query parameters for svfusion"}(e,t);n.skewer.push(...s)}if(t.queries.geneCnv){const s=await async function(e,t){if(e.gene){if(!t.queries.geneCnv.bygene)throw"q.gene provided but geneCnv.bygene missing";return await t.queries.geneCnv.bygene.get(e)}}(e,t);n.geneCnv=s}t.queries.cnv&&(n.cnv=await async function(e,t){if(e.rglst){if(!t.queries.cnv.byrange)throw"q.rglst provided but cnv.byrange missing";return await t.queries.cnv.byrange.get(e)}throw"insufficient query parameters for cnv"}(e,t)),function(e,t){if(t.skewer){const n=[];for(const s of t.skewer)e.rglst&&!e.rglst.find((e=>s.chr==e.chr&&s.pos>=e.start&&s.pos<=e.stop))||n.push(s);t.skewer=n}t.genecnvAtsample}(e,n),n.mclass2variantcount=function(e){const t=new Map;for(const n of e){const e=n.class||n.dt;t.set(e,1+(t.get(e)||0))}return[...t].sort(((e,t)=>t[1]-e[1]))}(n.skewer)}return function(e,t,n){const s=new Set;if(n.skewer)for(const r of n.skewer)if(r.samples){r.occurrence=r.samples.length,Ws(r,e,t),Vs(r,t);for(const e of r.samples)s.add(e.sample_id);delete r.samples}if(n.cnv)for(const e of n.cnv)if(e.samples)for(const n of e.samples)if(s.add(n.sample_id),t.cohort?.termdb?.q?.id2sampleName){const e=t.cohort.termdb.q.id2sampleName(n.sample_id);e&&(n.sample_id=e)}s.size&&(n.sampleTotalNumber=s.size)}(e,t,n),n}throw"do not know what client wants"}(r,o);n.send(i)}catch(e){n.send({error:e.message||e}),e.stack&&console.log(e.stack)}}}(Pr)),Jr.get(Hr+"/tkbampile",(async function(e,t){try{const[n,s,r]=F.ZX(e);if(n)throw n;let o=e.query.usegrade;const i=Number(e.query.allheight),a=Number(e.query.fineheight),l=Number(e.query.fineymax),c=Number(e.query.midpad),u=Number(e.query.regionspace),f=Number(e.query.width);if(!Number.isInteger(i))throw"allheight is not integer";if(!Number.isInteger(a))throw"fineheight is not integer";if(!Number.isInteger(l))throw"fineymax is not integer";if(!Number.isInteger(c))throw"midpad is not integer";if(!Number.isInteger(u))throw"regionspace is not integer";if(!Number.isFinite(f))throw"width is not a number";const d="string"==typeof e.query.rglst?JSON.parse(e.query.rglst):e.query.rglst;if(!d)throw"no rglst[]";if(!Array.isArray(d))throw"rglst is not an 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e=0;for(const n in t.data[o])e+=t.data[o][n];v=Math.max(v,e)}const w="#ededed";let _=0;const k=i/v,q=a/l;for(const e of d){const t=e.width/(e.stop-e.start);for(const n of e.items){const s=n.data[o];if(!s)continue;const r=e.scale(n.pos);let a=0;const u=[];for(const e in s)u.push({nt:e,v:s[e]}),a+=s[e];y.fillStyle=w;const f=k*(v-a);if(y.fillRect(_+r,f,t,k*a),u.length>1){u.sort(((e,t)=>t.v-e.v));for(let e=1;e<u.length;e++){let n=0;for(let t=0;t<e;t++)n+=u[t].v;y.fillStyle=$.basecolor[u[e].nt],y.fillRect(_+r,f+k*n,t,k*u[e].v)}}y.fillStyle=w;const d=i+c+q*(l-Math.min(a,l));if(y.fillRect(_+r,d,t,q*Math.min(a,l)),u.length>1)for(let e=1;e<u.length;e++){let n=0;for(let t=0;t<e;t++)n+=u[t].v;y.fillStyle=$.basecolor[u[e].nt],y.fillRect(_+r,d+q*(l-Math.min(l,a-n)),t,q*Math.min(l,u[e].v))}}_+=e.width+u}t.send({src:h.toDataURL(),allgrades:b,usegrade:o,allmax:v})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/dsdata",(async function(e,t){try{if(!Pr[e.query.genome])throw"invalid genome";if(!e.query.dsname)throw".dsname missing";const n=Pr[e.query.genome].datasets[e.query.dsname];if(!n)throw"invalid dsname";const s=[];for(const t of n.queries)if((!e.query.expressiononly||t.isgeneexpression)&&!(e.query.noexpression&&t.isgeneexpression||t.dsblocktracklst))if(t.vcffile){const n=await no(t,e);s.push(n)}else{if(!t.makequery)throw"unknow type from one of ds.queries[]";{const r=to(n,t,e);s.push(r)}}t.send({data:s})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Jr.post(Hr+"/tkbigwig",(async function(e,t){try{let n,s,o,i,a=!1,l=!1;const[c,u,f]=F.ZX(e);if(c)throw c;if(u.endsWith(".gz")&&(l=!0,f&&(i=await F.d1(u,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 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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 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Set,u=(i?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop;await F.UE({args:[s,u],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=z.parseheader(n[0],t,!0);if(s)throw"sv header line error: "+s;for(let e=1;e<n.length;e++)z.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=z.parseheader(n[0],t,!1);if(s)throw"fusion header line error: "+s;for(let e=1;e<n.length;e++)z.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=U.parseheader(n[0],t);if(s)throw"deletion header line error: "+s;for(let e=1;e<n.length;e++)U.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 u=c.split("\t"),f=Number.parseInt(u[1]),d=Number.parseInt(u[2]);if(n.file2){u[3];const t=u[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:f,stop:d,info:{type:{lst:[{attrValue:n}]}}},l=[];for(let e=5;e<u.length;e++){const t=u[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{u[3],u[4];if(!(f>=s.start&&f<=s.stop||d>=s.start&&d<=s.stop))return;o++;const c={chr:s.chr,start:f,stop:d,info:{type:{lst:[]}}},p=JSON.parse(u[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}),u=I().createInterface({input:a.stdout}),f=(t.stop-t.start)/t.width,d=[];for(let e=0;e<t.width;e++)d.push({positive:0,negative:0});u.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][zr]){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(t.start,r),p=Math.min(t.stop,i);let m,h;t.reverse?(m=Math.floor((t.stop-p)/f),h=Math.floor((t.stop-u)/f)):(m=Math.floor((u-t.start)/f),h=Math.floor((p-t.start)/f));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"),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",s/2,e.query.gain.barheight),u.src=r.toDataURL(),void t.send(u);for(const e of n)for(const t of e)u.maxvalue=Math.max(u.maxvalue,t.positive,t.negative);const f=e.query.maxvalue||u.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(f,n.positive)/f),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(f,n.negative)/f),s=e.query.gain.barheight;a.fillRect(d,s,1,t)}d++}d+=e.query.regionspace}if(u.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([zr,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}u.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++}u.hierarchySummary=n}}t.send(u)})).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,u,f;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=$.mdsvcftype.vcf,o.checkvcf={info:n.info,tracks:[n]}}if(e.query.checkrnabam){if(!e.query.checkrnabam.samples)return t.send({error:"samples{} missing from checkrnabam"});let n=0;for(const t in e.query.checkrnabam.samples)n++;if(n>13)return t.send({error:"no more than 13 BAM files allowed"});const s=fo(e.query.checkrnabam);if(s)return t.send({error:s});o.checkrnabam=e.query.checkrnabam}}else{if(n=Pr[e.query.genome],!n)return t.send({error:"invalid genome"});if(!n.datasets)return t.send({error:"genome is not equipped with datasets"});if(s=n.datasets[e.query.dslabel],!s)return t.send({error:"invalid dslabel"});if(e.query.getsample4disco)return function(e,t,n,s){if(e.query.iscustom)return t.send({error:"not for custom track"});if(!s.singlesamplemutationjson)return t.send({error:"singlesamplemutationjson not available for this dataset"});const o=e.query.getsample4disco,i=s.singlesamplemutationjson.samples[o];if(!i)return t.send({error:"no data"});const a=y().join(r().tpmasterdir,i);h().readFile(a,{encoding:"utf8"},((e,n)=>{if(e)return t.send({error:"error getting data for this sample"});t.send({text:n})}))}(e,t,0,s);if(e.query.gettrack4singlesample)return function(e,t,n){const s=e.query.gettrack4singlesample;if(e.query.iscustom)return t.send({error:"no server-side config available for custom track"});if(!n.sampleAssayTrack)return t.send({});return t.send({tracks:n.sampleAssayTrack.samples.get(s)})}(e,t,s);if(e.query.findsamplename)return function(e,t,n){if(e.query.iscustom)return t.send({error:"cannot search sample by name in custom track"});const s=e.query.findsamplename.toLowerCase(),r=[];if(!n.cohort.__samplelst){n.cohort.__samplelst=[];for(const e in n.cohort.annotation)n.cohort.__samplelst.push({name:e,low:e.toLowerCase()})}o(n.cohort.__samplelst);for(const e in n.queries){const t=n.queries[e];if(t.type==$.tkt.mdssvcnv&&t.groupsamplebyattr)for(const e of r){const s=n.cohort.annotation[e.name];if(!s)continue;const r=[];for(const 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Set(e.samplegroups[0].samples.map((e=>e.samplename))),n=new Set;for(const[e,r]of s)for(const e of r.samples.keys())t.has(e)||n.add(e);for(const t of n)e.samplegroups[0].samples.push({samplename:t,items:[]})}for(const n of e.samplegroups){const e=new Map;for(const[r,o]of s){e.set(r,[]);for(const[s,i]of o.samples)if(n.attributes&&t.cohort&&t.cohort.annotation){const o=t.cohort.annotation[s];if(!o)continue;let a=!0;for(const e of n.attributes)if(o[e.k]!=e.kvalue){a=!1;break}a&&e.get(r).push(i)}else e.get(r).push(i)}for(const[t,n]of e)n.sort(((e,t)=>e.value-t.value));for(const t of n.samples){t.expressionrank={};for(const[n,r]of e){const e=s.get(n).samples.get(t.samplename);if(null==e)continue;const o=vo(e.value,r);t.expressionrank[n]={rank:o};for(const s in e)t.expressionrank[n][s]=e[s]}}}}}(w,s,p,m);(function(e,t){if(e.cohort&&e.cohort.sampleAttribute&&e.cohort.sampleAttribute.attributes&&e.cohort.annotation){t.sampleannotation={};const n=[];for(const t in e.cohort.sampleAttribute.attributes){e.cohort.sampleAttribute.attributes[t].clientnoshow||n.push(t)}for(const s of t.samplegroups)for(const r of s.samples){const s=e.cohort.annotation[r.samplename];if(s){const e={};let o=!1;for(const t of n){const n=s[t];null!=n&&(o=!0,e[t]=n)}o&&(t.sampleannotation[r.samplename]=e)}}}})(s,w),t.send(w)})),Jr.post(Hr+"/mdsgenecount",(async function(e,t){try{const n=Pr[e.query.genome];if(!n)throw"invalid genome";if(!n.datasets)throw"no datasets from genome";const s=n.datasets[e.query.dslabel];if(!s)throw"invalid dataset";if(!s.gene2mutcount)throw"not supported on this dataset";if(!e.query.samples)throw".samples missing";let r,o;r=e.query.selectedMutTypes?e.query.selectedMutTypes.join("+"):"total",o=e.query.nGenes?e.query.nGenes:15;const i=`WITH\n\tfiltered AS (\n\t\tSELECT gene, ${r} AS total FROM genecount\n\t\tWHERE sample IN (${JSON.stringify(e.query.samples).replace(/[[\]\"]/g,"").split(",").map((e=>"'"+e+"'")).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=s.gene2mutcount.db.prepare(i).all(),l=[];for(const e of a){const t=n.genedb.getCoordByGene.get(e.gene);t&&(t.gene=e.gene,t.count=e.count,delete t.name,l.push(t))}t.send({genes:l})}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Jr.post(Hr+"/mds2",function(e){return async(t,n)=>{const s=t.query;try{const t=e[s.genome],r=await async function(e,t){if(!t)throw"invalid genome";if(e.dslabel){const n=t.datasets[e.dslabel];if(!n)throw"invalid dslabel";if(!n.track)throw"no mds2 track found for dataset";return n}const n={iscustom:1,track:{}};e.vcf&&(n.track.vcf=e.vcf,await F._H(n.track.vcf,t));e.ld;return n}(s,t);if(s.trigger_overlayld)return await async function(e,t,n){if(!e.ldtkname)throw".ldtkname missing";const s=t.track.ld.tracks.find((t=>t.name==e.ldtkname));if(!s)throw"ld tk not found by name: "+e.ldtkname;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 F.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,r,n);s.hidden_mclass&&(s.hidden_mclass=new Set(s.hidden_mclass));const o={mclass2count:{}};if(s.info_fields){o.info_fields={};for(const e of s.info_fields)if(e.iscategorical)o.info_fields[e.key]={value2count:{}};else if(e.isnumerical)o.info_fields[e.key]={filteredcount:0};else{if(!e.isflag)throw"unknown info type";o.info_fields[e.key]={count_yes:0,count_no:0}}}if(s.trigger_mafcovplot&&await async function(e,t,n,s){try{if(!n.track)throw"ds.track missing";const t=n.track.vcf;if(!t)throw"ds.track.vcf missing";if(n.iscustom)t.plot_mafcov={show_samplename:1};else if(!t.plot_mafcov)throw"maf-cov plot is not supported on this track";if(!e.m)throw".m{} missing";if(!t.AD)throw"vcf.AD{} missing";const r=(t.AD.nochr?e.m.chr.replace("chr",""):e.m.chr)+":"+(e.m.pos+1)+"-"+(e.m.pos+1),o=t.AD.chr2bcffile[e.m.chr];if(!o)throw"chr not in tk.AD.chr2bcffile";let i;if(await F.UE({isbcf:!0,args:["query","-r",r,"-f",fr,o],dir:t.AD.dir,callback:n=>{const[s,r,o]=D.S(n,t.AD);for(const t of r)if(t.pos==e.m.pos&&t.ref==e.m.ref&&t.alt==e.m.alt)return void(i=t)}}),!i)throw"variant not found";if(s.plotgroups=function(e,t,n){const s=[],r={name:"?",lst:[]};for(const s of e.sampledata){const o=s.AD[e.ref]||0,i=s.AD[e.alt]||0,a=o+i,l={mut:i,total:o+i,maf:0==a?0:i/a};t.plot_mafcov.show_samplename&&(l.sampleobj={name:n.cohort.termdb.q.id2sampleName(s.sampleobj.name)}),r.lst.push(l)}return s.push(r),s}(i,t,n),e.overlay_term){const t=await bs.g5({ds:n,term1_id:e.overlay_term,term1_q:e.overlay_term_q}),r=new Map;for(const e of t.lst)r.set(e.sample,e.key1);const o=(0,lr.Z)(cr),i=new Map;let a=0;for(const e of s.plotgroups)for(const 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=ur}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:ur,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=[],u=[];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&&u.push(t.sampleobj.name)}const f=Math.random().toString();s.ssid=f,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(u.length){const e="Homozygous alternative";s.groups[e]={size:u.length},d.push(e+"\t"+u.join(","))}await F.Sf(y().join(tr.cachedir_ssid,f),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}),u=I().createInterface({input:c.stdout}),f=new Map;u.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 f.has(r.gene)||f.set(r.gene,{chr:o,start:a,stop:l,allvalues:[]}),f.get(r.gene).thisvalue=r.value,void(r.ase&&(f.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),f.has(r.gene)||f.set(r.gene,{chr:o,start:a,stop:l,allvalues:[]}),f.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(f)}))})));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 u=c.join(", ");if(!a.has(u)){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(u,t)}a.get(u).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 u=[];for(const[e,t]of a)u.push({name:e,values:t.samples,attributes:t.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 e=u[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 f=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(u[0]){const e=u[0].values;if(e.sort(((e,t)=>t.value-e.value)),f)for(const t of e){const e=f.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 u){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(f){if(o.query.svcnv.usegain){const t=e.values.filter((e=>f.has(e.sample)&&f.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=>f.has(e.sample)&&f.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=>f.has(e.sample)&&f.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),u=i[a-1].genevalue,f=i[l-1].genevalue,d=i[c-1].genevalue;return[{name:r.gene+" "+o.datatype+" from 1st quartile (n="+a+", value<"+u+")",lst:i.slice(0,a),isfirstquartile:!0},{name:r.gene+" "+o.datatype+" from 2nd quartile (n="+(l-a)+", "+u+"<=value<"+f+")",lst:i.slice(a,l)},{name:r.gene+" "+o.datatype+" from 3rd quartile (n="+(c-l)+", "+f+"<=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 u;c.length>1&&(u=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 f={samplesets:c,pvalue:u};s.samplerule.set&&s.samplerule.set.mutation&&(f.count_snvindel=s.samplerule.set.samples_snvindel.size,f.count_cnv=s.samplerule.set.samples_cnv.size,f.count_loh=s.samplerule.set.samples_loh.size,f.count_sv=s.samplerule.set.samples_sv.size,f.count_fusion=s.samplerule.set.samples_fusion.size,f.count_itd=s.samplerule.set.samples_itd.size),n.send(f)}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,u=0;const f=[];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):u=Math.min(u,n.logpvaluediff),f.push(n));return{items:f,valuemin:u,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 u=!0,f=0,d=0;c.on("line",(i=>{if(u)return void(u=!1);const a=i.split(e.delimiter),c=[];for(const t of e.getpcd.coord)c.push(a[t]),f=Math.max(f,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(f),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 u=[],f=(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=f(t),u.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(u.filter((e=>e.category==t.value))[0])}for(const t of e.getgeneboxplot.cat_values)t.order||p.push(u.filter((e=>e.category==t.value))[0]);for(const t of u){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=u;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("")}(),u=JSON.stringify(e.body),f=s?hr(n,l):r().cachedir_massSession;await h().promises.access(f).then((()=>!0)).catch((()=>!1))||h().mkdirSync(f,{recursive:!0}),await F.Sf(y().join(f,c),u),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 u;try{u=(await h().promises.stat(c)).birthtime}catch(e){throw"invalid session"}const f=await F.b5(c),d=JSON.parse(f);if(e.query.route)return void t.send({state:d});const p=new Date,m=new Date(u),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=fo(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[u,f,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 u={info:i,format:a,samples:l},f=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 f||[]){const[n,s,r]=D.S(t,u);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,u,f);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,u=!1;n-t<=e.width?(u=!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 f=Number.parseInt(s[2]);if(!Number.isInteger(f))return;const d=e.rnabarheight*Math.min(f,r)/r,p=u?(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(),f>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:u,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 u=0;for(const n of t)n.dnacount&&(n.pos<r||n.pos>o||(n.__x=e.width*(n.pos-r)/(o-r),u=Math.max(u,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)/u;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 "+s;if(r.type==$.tkt.mdsjunction){const n=Do(r,e,t);if(n)throw s+" (mdsjunction) error: "+n}else if(r.type==$.tkt.mdscnv){const n=Go(r,e,t);if(n)throw s+" (mdscnv) error: "+n}else if(r.type==$.tkt.mdssvcnv){const n=Uo(r,e,t);if(n)throw s+" (svcnv) error: "+n}else{if(r.type!=$.tkt.mdsvcf)throw"unknown track type for a query: "+r.type+" "+s;{const n=await zo(r,e,t);if(n)throw s+" (vcf) error: "+n}}$o(r,e)}else{if(!r.isgenenumeric)throw"unknown type of query from "+s;{const n=Bo(r,e,t);if(n)throw s+" (genenumeric) error: "+n}}}if(e.track&&await Ys(e,t),e.annotationsampleset2matrix){if(!e.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!e.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!e.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!e.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!e.annotationsampleset2matrix.groups)throw".groups{} 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 $o(e,t){if(e.groupsamplebyattr){e.groupsamplebyattr.key2group=new Map;for(const n in t.cohort.annotation)uo(n,[],e.groupsamplebyattr.key2group,[],t,e)}}function Do(e,t,n){if(e.readcountCutoff&&(!Number.isInteger(e.readcountCutoff)||e.readcountCutoff<1))return"readcountCutoff must be positive integer";let s;if(e.file){const[t,n]=jo(e.file);if(t)return"tabix file error: "+t;e.file=n,s=n}else{if(!e.url)return"no file or url given for mdsjunction "+e.name;s=e.url}const r={encoding:"utf8"};const o=N().execSync(Gr+" -H "+s,r).trim();if(o){const n=o.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const s=n[0].split("\t");if(s[5]){e.samples=s.slice(5),e.attributeSummary=Lo(e.samples,t),e.hierarchySummary=Po(e.samples,t);for(const t in e.hierarchySummary){let n=0;for(const s in e.hierarchySummary[t])n++;console.log(n+" "+t+" hierarchy levels for "+e.name)}}}{const t=N().execSync(Gr+" -l "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=$.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 "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=$.contigNameNoChr(n,t.split("\n"))}console.log("("+e.type+") "+e.name+": "+(e.samples?e.samples.length:"no")+" samples, "+(e.nochr?'no "chr"':'has "chr"'))}function Uo(e,t,n){let s;if(e.file){const[t,n]=jo(e.file);if(t)return"tabix file error: "+t;s=n}else{if(!e.url)return"no file or url given for (svcnv) "+e.name;s=e.url}const r={encoding:"utf8"};const o=N().execSync(Gr+" -H "+s,r).trim();if(o){const n=new Set;for(const e of o.split("\n"))for(const t of e.split(" ").slice(1))n.add(t);if(0==n.size)return"no samples from the header line";if(e.samples=[...n],t.cohort&&t.cohort.annotation){const n=new Set;for(const s of e.samples)t.cohort.annotation[s]||n.add(s);n.size&&console.log("mdssvcnv unannotated samples: "+(e.noprintunannotatedsamples?n.size:[...n].join(" ")))}}{const t=N().execSync(Gr+" -l "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=$.contigNameNoChr(n,t.split("\n"))}if(e.expressionrank_querykey){const 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 groupsamplebyattr.attrlst[]";t.cohort.sampleAttribute.attributes[n.k]||(t.cohort.sampleAttribute.attributes[n.k]={label:n.label||n.k})}if(e.groupsamplebyattr.sortgroupby){if(!e.groupsamplebyattr.sortgroupby.key)return".key missing from .sortgroupby";if(!e.groupsamplebyattr.sortgroupby.order)return".order[] missing from .sortgroupby";if(!Array.isArray(e.groupsamplebyattr.sortgroupby.order))return".order must be an array"}e.groupsamplebyattr.attrnamespacer||(e.groupsamplebyattr.attrnamespacer=", ")}console.log("("+e.type+") "+e.name+": "+(e.samples?e.samples.length:"no")+" samples, "+(e.nochr?'no "chr"':'has "chr"'))}function Bo(e,t,n){if(!e.datatype)return"datatype missing";if(e.viewrangeupperlimit&&Number.isNaN(e.viewrangeupperlimit))return"invalid value for viewrangeupperlimit";let s;if(!e.file)return"file missing";{const[t,n]=jo(e.file);if(t)return"tabix file error: "+t;s=n}const r={cwd:null,encoding:"utf8"};{const t=N().execSync(Gr+" -H "+s,r).trim();if(!t)return"no header line (#sample <sample1> ...)";const n=new Set;for(const e of t.split("\n")){const t=e.split(" ");for(let e=1;e<t.length;e++)n.add(t[e])}if(0==n.size)return"no sample names from header line";e.samples=[...n],console.log("(genenumeric) "+e.name+": "+e.samples.length+" samples")}if(e.boxplotbysamplegroup){if(!e.boxplotbysamplegroup.attributes)return"boxplotbysamplegroup.attributes missing";if(!Array.isArray(e.boxplotbysamplegroup.attributes))return"boxplotbysamplegroup.attributes should be array";for(const t of e.boxplotbysamplegroup.attributes)if(!t.k)return"k missing from one of boxplotbysamplegroup.attributes[]"}}async function zo(e,t,n){if(!e.tracks)return"tracks[] missing";if(!Array.isArray(e.tracks))return"tracks should be array";e.info={};for(const s of e.tracks){if(!s.file)return"file missing from a track (url not supported yet)";const[r,o]=jo(s.file);if(r)return"tabix file error: "+r;if(s.type!=$.mdsvcftype.vcf)return"invalid track type: "+s.type;{s.cwd;const t=await F.ZD(o,s.cwd);if(0==t.length)return"no meta/header lines for "+o;const[n,r,i,a]=D.e(t);if(a)return"error parsing vcf meta for "+o+": "+a.join("\n");if(0==i.length)return"vcf file has no sample: "+o;for(const t in n)e.info[t]=n[t];if(s.format=r,s.samplenameconvert){if("function"!=typeof s.samplenameconvert)return".samplenameconvert must be function";for(const e of i)e.name=s.samplenameconvert(e.name)}s.samples=i}if(t.cohort&&t.cohort.annotation){const e=[];for(const n of s.samples)t.cohort.annotation[n.name]||e.push(n.name);e.length&&console.log(t.label+": VCF "+s.file+" has unannotated samples: "+e.join(","))}{const e=[];if(await F.UE({args:["-l",o],dir:s.cwd,callback:t=>{e.push(t)}}),0==e.length)return"no chr from "+o;s.nochr=$.contigNameNoChr(n,e)}console.log("("+e.type+") "+o+": "+s.samples.length+" samples, "+(s.nochr?"no chr":"has chr"))}if(e.singlesamples){if(!e.singlesamples.tablefile)return".singlesamples.tablefile missing for the VCF query";e.singlesamples.samples={};let t=0;for(const n of h().readFileSync(y().join(r().tpmasterdir,e.singlesamples.tablefile),{encoding:"utf8"}).trim().split("\n")){if(!n)continue;if("#"==n[0])continue;const s=n.split("\t");s[0]&&s[1]&&(e.singlesamples.samples[s[0]]=s[1],t++)}console.log(t+" single-sample VCF files")}}},6191:(e,t,n)=>{"use strict";n.d(t,{i:()=>y});var s=n(7147),r=n(1017),o=n.n(r),i=n(9344),a=n.n(i),l=n(8088);async function c(e,t){!function(e){for(const t in e){const n=e[t];if("login"==n.type){if(n.embedders)throw"unexpected 'embedders' property";n["*"]={"*":{type:"basic",password:n.password,secret:n.secret}},delete n.type,delete n.password}else if("jwt"==n.type){for(const e in n.embedders)n.termdb={[e]:Object.assign({type:n.type},n.embedders[e])},n.headerKey&&(n.termdb[e].headerKey=n.headerKey);delete n.type,delete n.embedders,delete n.headerKey}else if(n.type)throw`unknown legacy credentials type='${n.type}'`}}(e);const n="secrets";if("string"==typeof e[n]){const t=await s.promises.readFile(e[n],"utf8");e[n]=JSON.parse(t)}for(const t in e){const n=e[t];n["*"]&&(n["/**"]=n["*"],delete n["*"]);const s=n.headerKey||"x-ds-access-token";delete n.headerKey;for(const r in n){const o=n[r];for(const n in o){o[n]=JSON.parse(JSON.stringify(o[n]));const i=o[n],a="string"==typeof i?e.secrets[i]:i;if("basic"==a.type)a.secret||(a.secret=a.password),a.authRoute="/dslogin";else if("jwt"==a.type)a.authRoute="/jwt-status",a.headerKey||(a.headerKey=s);else if("forbidden"!=a.type&&"open"!=a.type)throw`unknown cred.type='${a.type}' for dsCredentials[${t}][${n}][${r}]`;a.dslabel=t,a.route=r,a.cookieId="termdb"==r&&a.headerKey||`${t}-${r}-${n}-Id`}}}}const u={termdb:["matrix"],samples:["singleSampleData","getAllSamples","scatter","convertSampleId","getAllSamplesByName"]};function f(e,t){return e.cookies?.[`${t?.cookieId}`]||e.cookies?.[`${e.query.dslabel}SessionId`]||e.headers?.["x-sjppds-sessionid"]||e.query?.["x-sjppds-sessionid"]}async function d(e,t,n,r,o,i,l=""){if(r.secret)try{const c=Date.now(),u=Math.floor(c/1e3),f={dslabel:t.dslabel,id:n,iat:u,time:c,ip:e.ip,embedder:t.embedder,route:r.route,exp:u+Math.floor(o/1e3),email:l};r.dsnames&&(f.datasets=r.dsnames.map((e=>e.id)));const d=a().sign(f,r.secret);return await s.promises.appendFile(i,`${t.dslabel}\t${n}\t${c}\t${l}\t${e.ip}\t${t.embedder}\t${r.route}\n`),d}catch(e){throw e}}function p(e,t,n,s,r){if(!s.headers.authorization||n&&e[t]?.[n])return;if(!r.secret)throw{status:"error",error:`no credentials set up for this embedder='${s.query.embedder}'`,code:403};const[o,i]=s.headers.authorization.split(" ");if("bearer"!=o.toLowerCase())throw`unsupported authorization type='${o}', allowed: 'Bearer'`;const c=Buffer.from(i,"base64").toString();try{const o=a().verify(c,r.secret);if(n&&o.id!=n&&s.headers?.["x-sjppds-sessionid"]!=o.id)return;e[t]||(e[t]={});const i="/"!=s.path[0]||r.route.startsWith("/")?s.path:s.path.slice(1);if((0,l.isMatch)(i,r.route)||"authorizedActions"==i)return e[t][o.id]=o,o.id}catch(e){return}}async function m(e,t,n,r,o,i,a){const l=Date.now(),c=Math.random().toString()+"."+l.toString().slice(4),u=i.ip;return n[e.dslabel]||(n[e.dslabel]={}),n[e.dslabel][c]={id:c,time:l,email:o,ip:u},await s.promises.appendFile(r,`${e.dslabel}\t${c}\t${l}\t${o}\t${u}\t${e.embedder}\t${a.route}\n`),a.cookieMode&&"set-cookie"!=a.cookieMode||t.header("Set-Cookie",`${a.cookieId}=${c}; HttpOnly; SameSite=None; Secure`),c}function h(e,t,n,s,r=null){if(!n)return;if(!e.embedder)throw"missing q.embedder";const o=n.secret;if(!o)throw{status:"error",error:"no credentials set up for this embedder",code:403};const i=Math.floor((s||Date.now())/1e3),l=t[n.headerKey];if(!l)throw`missing header['${n.headerKey}']`;const c=n.processor?require(n.processor):{},u=c.handleToken?.(l)||l,f=a().verify(u,o);if(r)return{iat:f.iat,email:f.email,ip:f.ip};if(c.handlePayload)try{c.handlePayload(n,f,i)}catch(e){if("bad decrypt"==e.reason)throw`Please login again to access this feature. (${e.reason})`;throw e}if(i>f.exp)throw"Please login again to access this feature. (expired token)";const d=(n.dsnames||[e.dslabel]).filter((e=>!f.datasets?.includes(e.id))).map((e=>e.id));if(d.length)throw{error:"Missing access",linkKey:d.join(",")};return{iat:f.iat,email:f.email,ip:f.ip}}function g(e,t,n){if(!n.looseIpCheck||!e.ip?.includes(":")&&t){if(!t)throw"Server error: missing ip address in saved session";if(e.ip!=t&&e.ips?.[0]!=t&&e.connection?.remoteAddress!=t)throw"Your connection has changed, please refresh your page or sign in again."}}const y={maySetAuthRoutes:async function(e,t="",r=null){const i=r||n(334),b=i.features?.sessionTracking||"",v=o().join(i.cachedir,"dsSessions"),w=o().join(i.cachedir,"authorizedActions"),_=i.dsCredentials||{};delete i.dsCredentials;const k=i.maxSessionAge||576e5;let q;if(!_||!Object.keys(_).length)return y.getDsAuth=()=>[],y.getForbiddenRoutesForDsEmbedder=()=>[],y.userCanAccess=()=>!0,y.getRequiredCredForDsEmbedder=()=>{},void(y.getPayloadFromHeaderAuth=()=>({}));try{c(_)}catch(e){throw e}function x(e,t,n){if(!e.dslabel)return;const s=_[e.dslabel]||_["*"];if(s){if("/jwt-status"==t){const t=s[e.route]||s.termdb||s["/**"];return t&&(t[e.embedder]||t["*"])}if("/dslogin"==t){const t=s[e.route]||s["/**"];return t&&(t[e.embedder]||t["*"])}if(t.startsWith("/termdb")&&s.termdb){const t=s.termdb;return(n||u.termdb).includes(e.for)&&(t[e.embedder]||t["*"])}if(t.startsWith("/burden")&&s.burden)return s.burden[e.embedder]||s.burden["*"]}for(const n in _){if(n!=e.dslabel&&"*"!=n)continue;const s=_[n];for(const n in s){const r=s[n].routePattern||n;if(!(0,l.isMatch)(t,r))continue;const o=s[n];for(const t in o)if(t==e.embedder||"*"==t)return o[t]}}}e.use(((e,t,n)=>{if("/dslogin"==e.path||"/jwt-status"==e.path||"/dslogout"==e.path)return void n();const s=e.query,r=x(s,e.path);if(!r)return void n();let o;"jwt-only"==b&&(q={});try{const i=f(e,r);let a;if(!i){if("OPTIONS"==e.method.toUpperCase())return t.status(204),void t.send();if(a=p(q,s.dslabel,i,e,r),!a)throw o=401,"missing session cookie"}a||(a=p(q,s.dslabel,i,e,r));const l=q[s.dslabel]?.[i]||q[s.dslabel]?.[a];if(!l)throw o=401,"unestablished or expired browser session";g(e,l.ip,r);const c=Date.now();if(c-l.time>k){const{iat:t}=h(s,e.headers,r,l),n=c-t;if(n>k)throw delete q[s.dslabel][i],"Please login again to access this feature. 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authorization route, use '${r.authRoute}'`;if(!e.headers.authorization)throw"missing authorization header";const[o,i]=e.headers.authorization.split(" ");if("basic"!=o.toLowerCase())throw`unsupported authorization type='${o}', allowed: 'Basic'`;if(Buffer.from(i,"base64").toString()!=r.password)throw"invalid password";const a=await m(s,t,q,v,"",e,r);n=401;const l=await d(e,s,a,r,k,v);t.send({status:"ok",jwt:l,route:r.route})}catch(e){t.status(n),t.send({error:e})}})),e.post(t+"/dslogout",(async(e,t)=>{try{const n=e.query,r=f(e,x(n,e.path));if(!r)throw"missing session cookie";const o=q[n.dslabel]?.[r];if(!o)return void t.send({status:"ok"});delete q[n.dslabel][r];e.ip;await s.promises.appendFile(v,`${n.dslabel}\t${r}\t0\t\t${o.ip}\t${o.embedder}\t${o.route}\n`),t.send({status:"ok"})}catch(e){t.status(401),t.send({error:e})}})),e.post(t+"/jwt-status",(async(e,t)=>{let n=401;try{const s=e.query,r=x(s,e.path);if(!r)return void t.send({status:"ok"});if("/jwt-status"!=r.authRoute)throw n=400,`Incorrect authorization route, use ${r.authRoute}'`;const{email:o,ip:i}=await h(s,e.headers,r);g(e,i,r);const a=await m(s,t,q,v,o,e,r);n=401;const l=await d(e,s,a,r,k,v,o);t.send({status:"ok",jwt:l,route:r.route,[r.cookieId]:a})}catch(e){console.log(e),t.status(n),t.send(e instanceof Error||"object"!=typeof e?{error:e}:e)}})),e.post(t+"/authorizedActions",(async(e,t)=>{const n=e.query;try{const r=x(n,"termdb");if(!r)return void t.send({status:"ok"});const o=f(e),i=p(q,n.dslabel,o,e,r),a=q[n.dslabel]?.[o]||q[n.dslabel]?.[i],{email:l}=a.email,c=new Date;await s.promises.appendFile(w,`${n.dslabel}\t${l}\t${c}\t${n.action}\t${JSON.stringify(n.details)}\n`),t.send({status:"ok"})}catch(e){t.status(401),t.send("object"==typeof e?e:{error:e})}})),y.getDsAuth=function(e){const t=[],n=e.query.embedder||e.get("host").split(":")[0];for(const s in _){if(s.startsWith("__"))continue;const r=_[s];for(const o in r){const i=r[o];for(const r in i){if(!(0,l.isMatch)(n,r))continue;const a=i[r],c=f({query:Object.assign({},e.query,{dslabel:s}),headers:e.headers,cookies:e.cookies},a),u=q[s]?.[c],d=u?.time||0;t.push({dslabel:s,route:o,type:a.type||"basic",insession:("basic"!=a.type||!e.path.startsWith("/genomes"))&&(("jwt"!=a.type||c)&&Date.now()-d<k)})}}}return t},y.getForbiddenRoutesForDsEmbedder=function(e,t){const n=[],s=_[e]||_["*"];if(!s)return n;for(const e in s){const r=s[e][t]||s[e]["*"];"forbidden"==r?.type&&n.push(e)}return n},y.getRequiredCredForDsEmbedder=function(e,t){const n=[];for(const s in _)if((0,l.isMatch)(e,s))for(const e in _[s])for(const r in _[s][e]){if(!(0,l.isMatch)(t,r))continue;const o=_[s][e][r];n.push({route:e,type:o.type,headerKey:o.headerKey})}return n},y.userCanAccess=function(e,t){const n=x(e.query,e.path,u.samples);if(!n)return!0;if("basic"==n.type&&e.path.startsWith("/genomes"))return!1;const s=f(e,n),r=p(q,t.label,s,e,n),o=q[t.label]?.[s]||q[t.label]?.[r],i=o?.time||0;return 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),u=n(8064),f=n(5494),d=n(6733),p=n(5558),m=n(3602),h=n(6279);const g={snvindel:f,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=u.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 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n=ie,s=le,{host:r,headers:o}=t.getHostHeaders(e),i=C.post(T().join(r.rest,n.endpoint),{headers:o,json:Object.assign({size:n.size,fields:n.fields.join(",")},n.filters(e))}).json(),a=C.post(T().join(r.rest,s.endpoint),{headers:o,json:Object.assign({size:s.size,fields:s.fields.join(",")},s.filters(e,t))}).json(),[l,c]=await Promise.all([i,a]);if(!Array.isArray(l?.data?.hits)||!Array.isArray(c?.data?.hits))throw"ssm tandem query not returning data.hits[]";const u=new Map;for(const t of l.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=[],u.set(t.ssm_id,t)}for(const e of c.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=u.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[...u.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(z(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 B(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 z(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 J(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(O("string"==typeof e.filterObj?JSON.parse(e.filterObj):e.filterObj)),t}e.queries.geneCnv.bygene.get=async t=>{const{host:o,headers:i}=e.getHostHeaders(t),a=await C.post(T().join(o.rest,"cnv_occurrences"),{headers:i,json:Object.assign({size:1e5,fields:n(t)},r(t))}).json();if(!Array.isArray(a?.data?.hits))throw"geneCnv response body is not {data:hits[]}";const l={ssm_id:"geneCnvGain",dt:s.dtcnv,class:s.mclasscnvgain,samples:[]},c={ssm_id:"geneCnvLoss",dt:s.dtcnv,class:s.mclasscnvloss,samples:[]};for(const e of a.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=l;else{if("Loss"!=e.cnv.cnv_change)throw"hit.cnv.cnv_change is not Gain/Loss";n=c}const s={sample_id:e.case.case_id};if(t.twLst)for(const n of t.twLst)W(s,e.case,n);n.samples.push(s)}const u=[];return l.samples.length&&u.push(l),c.samples.length&&u.push(c),u}}function H(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 W(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 V(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]=Z(o,e))}}else if("continuous"!=s.q.mode)throw"mayApplyBinning: unknown numeric q.mode";return n}function Z(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 K(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 X(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(O(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"],i=new Map;for(const e of r){const t=e.term.id.replace(/^case\./,"");o.push(t),i.set(t,e.term.id)}const{host:a,headers:l}=n.getHostHeaders(e),c=await C.post(T().join(a.rest,"cases"),{headers:l,json:{size:n.__gdc.casesWithExpData.size,fields:o.join(","),case_filters:s.content.length?s:void 0}}).json();if(!Array.isArray(c?.data?.hits))throw"re.data.hits[] not array";const u=[];for(const e of c.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)W(t,e,n);u.push(t)}const f=V(u,r);return{byTermId:f,samples:u}}(e,t,n);if(K(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 i={size:1e4,fields:o.join(",")};B(e,n),Object.assign(i,le.filters(e,n));const{host:a,headers:l}=n.getHostHeaders(e),c=await C.post(T().join(a.rest,le.endpoint),{headers:l,json:i}).json();if(delete e.isoforms,!Array.isArray(c?.data?.hits))throw"variant2samples re.data.hits is not array for query";const u=[];for(const t of c.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(z(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)W(s,t.case,e);Y(t.case,s),Q(s,n),u.push(s)}const f=V(u,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)u.push(t)}const d=new Map;for(const e of u)(0,M.z9)([e],d,e.ssm_id);return{byTermId:f,samples:[...d.values()]}}function Y(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 Q(e,t){const n=e["case.project.project_id"];n&&(e.caseIsOpenAccess=t.__gdc.gdcOpenProjects?.has(n))}async function ee(e,t,n,s){K(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),i=function(e,t){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};ce(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(O(e.filterObj));return n}(t,s),{host:a,headers:l}=s.getHostHeaders(t),c=["data","explore","cases","aggregations"];let u=(await C.post(a.graphql,{headers:l,json:{query:o,variables:i}}).json())[c[0]];for(let e=1;e<c.length;e++)if(u=u[c[e]],!u)throw`.${c[e]} missing from data structure of termid2totalsize2 for query :${o} and filter: ${filter}`;for(const e of r){if("categorical"==e.type&&!Array.isArray(u[e.path].buckets))throw c.join(".")+" not array for query :"+o+" and filter: "+filter;if(("integer"==e.type||"float"==e.type)&&"object"!=typeof u[e.path].stats)throw c.join(".")+" not object for query :"+o+" and filter: "+filter}const f=new Map;for(const e of r)if("categorical"==e.type){const t=u[e.path].buckets,n=[];for(const e of t)n.push([e.key.replace(".","__"),e.doc_count]);f.set(e.id,n)}else if("integer"==e.type||"float"==e.type){const t=u[e.path].stats.count;f.set(e.id,{total:t})}return n?[f,n]:f}function te(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 C(s.rest+"/ssms/"+n.ssm_id+"?fields="+t.join(","),{headers:r}).json();if(!o.data||!o.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(o.data.consequence))throw".data.consequence not array";return o.data.consequence.map((e=>e.transcript))}}function ne(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 se(t.sample,e)));return await async function(e,t,n){const r={mlst:[],dt2total:[]};{const{host:n,headers:o}=t.getHostHeaders(e),i=await C.post(T().join(n.rest,ie.endpoint),{headers:o,json:{size:1e4,fields:ie.fields.join(","),filters:ie.filters(e).filters}}).json();if(!Number.isInteger(i.data?.pagination?.total))throw"re.data.pagination.total not integer";if(!Array.isArray(i.data?.hits))throw"re.data.hits[] not array";i.data.hits.length<i.data.pagination.total&&r.dt2total.push({dt:1,total:i.data.pagination.total});for(const e of i.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 C.post(T().join(n.rest,"files"),{headers:r,json:{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)}}).json();if(!Array.isArray(o.data.hits))throw"re.data.hits[] not array";let i,a,l;for(const e of o.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;i=e.file_id;continue}if("WGS"==e.experimental_strategy){if(!e.file_id)continue;if("Copy Number Segment"!=e.data_type)continue;a=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;l=e.file_id}const c=[];if(a){const e=(await C(T().join(n.rest,"data",a),{headers:r}).text()).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)||(c.push(a),r>0&&0==i&&o>0&&c.push({dt:s.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(i){const e=(await C(T().join(n.rest,"data",i),{headers:r}).text()).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)||c.push(r)}}if(l)try{const e=(await C(T().join(n.rest,"data",l),{headers:r}).text()).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)&&(H(r,n[6]),c.push(r))}}catch(e){}return c}(e,t);r.mlst.push(...n)}return r}(t,e)}}async function se(e,t){const{host:n,headers:s}=t.getHostHeaders(q),r=await C.post(T().join(n.rest,"cases"),{headers:s,json:{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]}}]}}}).json();console.log(r);for(const e of r.data.hits)if(e.case_id)return e.case_id;throw"cannot convert to case_id (uuid)"}function re(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 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missing";a.get(s).experiments.push({experimentID:t,sampleName:n.samples[0].submitter_id,sampleType:n.samples[0].sample_type})}return{samples:[...a.values()]}}}function oe(e,t){e.queries.singleCell.data.get=async t=>{const{host:n,headers:s}=e.getHostHeaders(t),r=(await C(T().join(n.rest,"data",t.sample),{headers:s}).text()).trim().split("\n"),o={name:"UMAP",cells:[],colorBy:"Cluster"},i={name:"TSNE",cells:[],colorBy:"Cluster"},a={name:"PCA",cells:[],colorBy:"Cluster"},l={id:"cluster",name:"Seurat cluster",type:"categorical",values:{}},c={[l.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 u=n[3];if(!u)throw"seuratCluster missing from a line";l.values[u]={label:"Cluster "+u},c[l.id][s]=`Cluster ${u}`;const f=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(f))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 ${u}`;o.cells.push({cellId:s,x:f,y:d,category:y}),i.cells.push({cellId:s,x:p,y:m,category:y}),a.cells.push({cellId:s,x:h,y:g,category:y})}return{plots:[i,o,a],terms:[l],tid2cellvalue:c}}}const ie={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],ae(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(O(e.filterObj)),t}};function ae(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 le={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],ae(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(O(e.filterObj)),ce(e.tid2value,n.case_filters.content,t),n}};function ce(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:()=>f,uK:()=>d});var s=n(1881),r=n(4555),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),u=n(2974);const f=".";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(f);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,u]=r,f=decodeURIComponent(u),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==f&&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}]}),u=await n.queries.snvindel.byrange.get(c);for(const e of u)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,u.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 s){if(n.id0){if(!n.v0)continue;o.get(n.id0).add(t.cohort.termdb.useLower?n.v0.toLowerCase():n.v0)}if(n.id1&&e[1]){if(!n.v1)continue;o.get(n.id1).add(t.cohort.termdb.useLower?n.v1.toLowerCase():n.v1)}if(n.id2&&e[2]){if(!n.v2)continue;o.get(n.id2).add(t.cohort.termdb.useLower?n.v2.toLowerCase():n.v2)}}const a=e[0].id;{const s={};n.filterObj&&(s.filterObj=n.filterObj),n.filter0&&(s.filter0=n.filter0);const l=await t.cohort.termdb.termid2totalsize2.get([e[0]],s);for(const[e,n]of l.get(a)){const s=t.cohort.termdb.useLower?e.toLowerCase():e;i?(o.get(a).add(s),r.push({count:n,id0:a,v0:s})):o.get(a).has(s)&&r.push({count:n,id0:a,v0:s})}}const l=e?.[1]?.id;if(l){const s=[];for(const r of o.get(a)){const o={tid2value:{[a]:r}};n.filterObj&&(o.filterObj=n.filterObj),n.filter0&&(o.filter0=n.filter0),s.push(t.cohort.termdb.termid2totalsize2.get([e[1]],o,r))}const c=await Promise.all(s);for(const[e,n]of c)for(const[s,c]of e.get(l)){const e=t.cohort.termdb.useLower?s.toLowerCase():s;i?(o.get(l).add(e),r.push({count:c,id0:a,v0:n,id1:l,v1:e})):o.get(l).has(e)&&r.push({count:c,id0:a,v0:n,id1:l,v1:e})}}const c=e?.[2]?.id;if(c){const s=[];for(const r of o.get(a))for(const i of o.get(l)){const o={tid2value:{[a]:r,[l]:i}};n.filterObj&&(o.filterObj=n.filterObj),n.filter0&&(o.filter0=n.filter0),s.push(t.cohort.termdb.termid2totalsize2.get([e[2]],o,{v0:r,v1:i}))}const u=await Promise.all(s);for(const[e,n]of u)for(const[e,s]of v2counts.get(c)){const u=t.cohort.termdb.useLower?e.toLowerCase():e;i?(o.get(c).add(u),r.push({count:s,id0:a,v0:n.v0,id1:l,v1:n.v1,id2:c,v2:u})):o.get(c).has(u)&&r.push({count:s,id0:a,v0:n.v0,id1:l,v1:n.v1,id2:c,v2:u})}}return r}(n.twLst,t,n,r);await async function(e,t,n){for(const s of e){if(!s.id0)continue;if(!s.v0)continue;const e=n.cohort.termdb.useLower?s.v0.toLowerCase():s.v0;if(!s.id1){const n=t.find((t=>null==t.id1&&t.v0==e));n&&(s.cohortsize=n.count);continue}if(!s.v1)continue;const r=n.cohort.termdb.useLower?s.v1.toLowerCase():s.v1;if(!s.id2){const n=t.find((t=>null==t.id2&&t.v0==e&&t.v1==r));n&&(s.cohortsize=n.count);continue}if(!s.v2)continue;const o=n.cohort.termdb.useLower?s.v2.toLowerCase():s.v2;if(!s.id3){const t=crosstabL2.find((t=>t.v0==e&&t.v1==r&&t.v2==o));t&&(s.cohortsize=t.count)}}}(r,e,t)}return r}(n.samples,t,e),delete n.samples,n;if(e.get==t.variant2samples.type_summary)return n.summary=await async function(e,t,n){if(!n.twLst)throw"q.twLst[] missing for make_summary()";const s=[];for(const t of n.twLst)if(t.term)if("categorical"==t.term.type){const n=g(e,t.id);s.push({termid:t.id,numbycategory:[...n].sort(((e,t)=>t[1]-e[1]))})}else{if("integer"!=t.term.type&&"float"!=t.term.type)throw"unknown term type";{const n=await a(t.term,e);s.push({termid:t.id,density_data:n})}}if(t.cohort.termdb.termid2totalsize2){const e=await t.cohort.termdb.termid2totalsize2.get(n.twLst,n);for(const{termid:t,numbycategory:n}of s){if(!n)continue;const s=e.get(t);if(s)for(const e of n){const t=s.find((t=>t[0].toLowerCase()==e[0].toLowerCase()));t&&e.push(t[1])}}}return s}(n.samples,t,e),delete n.samples,n;throw"unknown get type"}(t,e)}}function p(e,t,n){for(const s of e){t.has(s.sample_id)||(s.ssm_id_lst=[],s.formatK2v&&(s.ssmid2format={}),t.set(s.sample_id,s));const e=t.get(s.sample_id);e.ssm_id_lst.push(n),e.ssmid2format&&(e.ssmid2format[n]=s.formatK2v)}}function m(e,t,n){if(t)for(const s of e.values())for(const e of t){const t=n.cohort.termdb.q.getSample2value(e.id,s.sample_id);t[0]&&(s[e.id]=t[0].value)}}async function h(e,t,n){const s=new Map;if(n.queries.snvindel){const t=await n.queries.snvindel.byrange.get(e);for(const e of t)p(e.samples,s,e.ssm_id)}if(n.queries.svfusion){const t=await n.queries.svfusion.byrange.get(e);for(const e of t)p(e.samples,s,e.ssm_id)}if(n.queries.cnv){const t=await n.queries.cnv.byrange.get(e);for(const e of t)p(e.samples,s,e.ssm_id)}return m(s,t,n),{samples:[...s.values()]}}function g(e,t){const 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n=e.name;if("geneVariant"==e.type){if(!t[n]||!t[n].values)return"Wildtype";const e=t[n].values.filter((e=>"Blank"!=e.class));return e.find((e=>"WT"!=e.class))?`${n} Variant`:e.find((e=>"WT"==e.class))?`${n} Wildtype`:t[n].values.length>e.length?"Not tested":"Not sure"}throw`cannot get series key for term='${n}'`}var _=n(8599),k=n(3795),q=n(1575),x=n(2188);var N=n(478),S=n(1271);async function A(e,t,n,s){!function(e,t){if(!e.chr)throw"q.chr missing";if(e.start=Number(e.start),e.stop=Number(e.stop),!Number.isInteger(e.start)||!Number.isInteger(e.stop))throw"q.start/stop is not integer";if("object"!=typeof e.details)throw"q.details{} not object";if(!Array.isArray(e.details.groups))throw"q.details.groups[] not array";if(!e.details.groups[0])throw"q.details.groups[0] missing";if(e.details.groups.length>2)throw"q.details.groups[] has more than 2";for(const n of e.details.groups)if("filter"==n.type){if("object"!=typeof n.filter)throw".filter not an object for group type=filter"}else 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o=j(await t.queries.snvindel.byrange.get(n));n.filterObj=T(e,r.filter);const i=j(await t.queries.snvindel.byrange.get(n)),a=function(e,t,n){const[s,r]=n.details.groups,o=[];for(const n of e){n.groupData=[{refCount:n._refCount,altCount:n._altCount}];const e=t.find((e=>e.chr==n.chr&&e.pos==n.pos&&e.ref==n.ref&&e.alt==n.alt));e?n.groupData.push({refCount:e._refCount,altCount:e._altCount}):n.groupData.push({refCount:0,altCount:0}),o.push(n)}for(const n of t){e.find((e=>e.chr==n.chr&&e.pos==n.pos&&e.ref==n.ref&&e.alt==n.alt))||(n.groupData=[{refCount:0,altCount:0},{refCount:n._refCount,altCount:n._altCount}],o.push(n))}return o}(o.mlst,i.mlst,e);return{mlst:a,totalSampleCount_group1:C(o.mlst),totalSampleCount_group2:C(i.mlst)}}n.filterObj=T(e);const o=await t.queries.snvindel.byrange.get(n),i=j(o);"filter"==s.type?i.totalSampleCount_group1=C(o):"filter"==r?.type&&(i.totalSampleCount_group2=C(o));return i}(e,n);if(1==e.details.groups.length)M(n,r.mlst,e.details.groups[0]);else{if(2!=e.details.groups.length)throw"q.details.groups.length not 1 or 2";await async function(e,t,n){const[s,r]=t.groups;if("filter"==s.type&&"filter"==r.type)return void await async function(e,t,n){const s=t.groupTestMethods[t.groupTestMethodsIdx];if(!s)throw"details.groupTestMethodsIdx out of bound";switch(s.name){case"Allele frequency difference":return void I(e,t,n);case"Fisher's exact test":return void await F(n);default:throw"unknown value from groupTestMethods[]"}}(e,t,n.mlst);if("population"==s.type&&"filter"==r.type||"population"==r.type&&"filter"==s.type)return void await async function(e,t,n){const s=await async function(e,t,n){const s=t.groups.find((e=>"population"==e.type));if(!s)return;if(!s.adjust_race)return;const r=e.queries.snvindel.populations.find((e=>e.key==s.key));if(!r)throw"invalid group.key for population";const o=new Set;for(const e of n.mlst)for(const t of e.samples)o.add(t.sample_id);const i=new Map;let a=0;for(const t of r.sets){const n={infokey_AC:t.infokey_AC,infokey_AN:t.infokey_AN,average:0},s=await(0,c.J4)({ds:e,key:t.key});for(const e of s){if(!o.has(e.sample))continue;const t=Number(e.value);Number.isFinite(t)&&(n.average+=t,a+=t)}i.set(t.key,n)}for(const[e,t]of i)t.average/=a;n.pop2average={};for(const[e,t]of i)n.pop2average[e]=t.average;return i}(e,t,n);for(const r of n.mlst)r.groupData=E(e,t,r,s);const r=t.groupTestMethods[t.groupTestMethodsIdx];if(!r)throw"details.groupTestMethodsIdx out of bound";switch(r.name){case"Allele frequency difference":return void I(e,t,n.mlst);case"Fisher's exact test":return void await F(n.mlst);default:throw"unknown value from groupTestMethods[]"}}(e,t,n);I(e,t,n.mlst)}(n,e.details,r)}for(const e of r.mlst)delete e.samples,delete e._altCount,delete e._refCount;t.send(r)}function C(e){const t=new Set;for(const n of e)if(n.samples)for(const e of n.samples)t.add(e.sample_id);return t.size}function j(e){const t={mlst:[],skipMcountWithoutAlt:0};for(const n of e){const[e,s]=O(n);0!=e?(n._altCount=e,n._refCount=s-e,t.mlst.push(n)):t.skipMcountWithoutAlt++}return t}function T(e,t){const n=[e.filter];if(t)n.push(t);else for(const t of e.details.groups)"filter"==t.type&&n.push(t.filter);return(0,N.xH)(n)}function M(e,t,n){if("filter"!=n.type)if("info"!=n.type){if("population"!=n.type)throw"unknown type of single group";{const s=e.queries.snvindel.populations.find((e=>e.key==n.key));if(!s)throw"unknown population";for(const e of t){let t=0,n=0;for(const r of s.sets)t+=Number(e.info[r.infokey_AC]||0),n+=Number(e.info[r.infokey_AN]||0);e.nm_axis_value=t/n}}}else{if(!n.infoKey)throw"infoKey missing on single group.type=info";for(const e of t){const t=e.info[n.infoKey];if(null==t);else{const n=Number(t);Number.isNaN(n)||(e.nm_axis_value=n)}}}else for(const e of t)e.nm_axis_value=Number((e._altCount/(e._altCount+e._refCount)).toPrecision(2))}function O(e){let t=0,n=0;for(const s of e.samples){if(!s?.formatK2v?.GT)continue;const r=s.formatK2v.GT.split("/").map(Number);n+=r.length;for(const n of r)n==e.altAlleleIdx&&t++}return[t,n]}function 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 e)i.ANadj=n*t.get(o).average,i.ACadj=0==i.ANadj?0:i.ACraw*i.ANadj/i.ANraw,s+=i.ACadj,r+=i.ANadj;return[r-s,s]}async function F(e){for(let t=0;t<Math.ceil(e.length/200);t++){const n=[];for(let s=200*t;s<200*(t+1);s++){const t=e[s];if(!t)break;const r=t.groupData;r&&r[0]&&r[1]&&Number.isFinite(r[0].altCount)&&Number.isFinite(r[0].refCount)&&Number.isFinite(r[1].altCount)&&Number.isFinite(r[1].refCount)?(n.push({index:s,n1:Math.floor(r[0].altCount),n2:Math.floor(r[0].refCount),n3:Math.floor(r[1].altCount),n4:Math.floor(r[1].refCount)}),t.htmlSections=[{key:"Contigency table",html:`<table style="font-size:.9em">\n\t\t\t\t<tr style="opacity:.5">\n\t\t\t\t <td></td>\n\t\t\t\t <td>Group1</td>\n\t\t\t\t <td>Group 2</td>\n\t\t\t\t</tr>\n\t\t\t\t<tr>\n\t\t\t\t <td style="opacity:.5">ALT allele count</td>\n\t\t\t\t <td>${r[0].altCount}</td>\n\t\t\t\t <td>${Math.floor(r[1].altCount)}</td>\n\t\t\t\t</tr>\n\t\t\t\t<tr>\n\t\t\t\t <td style="opacity:.5">REF allele count</td>\n\t\t\t\t <td>${r[0].refCount}</td>\n\t\t\t\t <td>${Math.floor(r[1].refCount)}</td>\n\t\t\t\t</tr>\n\t\t\t\t<tr>\n\t\t\t\t <td style="opacity:.5">Allele frequency</td>\n\t\t\t\t <td>${(r[0].altCount/(r[0].altCount+r[0].refCount)).toFixed(3)}</td>\n\t\t\t\t <td>${(r[1].altCount/(r[1].altCount+r[1].refCount)).toFixed(3)}</td>\n\t\t\t\t</tr>\n\t\t\t\t</table>`}]):console.log(`${t.chr}.${t.pos}.${t.ref}.${t.alt}\t${JSON.stringify(r)}`)}const s=await(0,S.run_rust)("fisher",JSON.stringify({input:n}));for(const t of JSON.parse(s)){const n=e[t.index];n&&(n.p_value=t.p_value.toPrecision(2),t.p_value>0&&(n.nm_axis_value=Number((-Math.log10(t.p_value)).toPrecision(2))))}}let t=0;for(const n of e)n.p_value>0&&(t=Math.max(t,n.nm_axis_value));for(const n of e)0==n.p_value&&(n.nm_axis_value=Math.max(50,t))}var $=n(4065),D=n(3936);function L(e){return async(t,n)=>{const s=t.query;(0,h.Y5)(s,t.cookies);try{const r=e[s.genome];if(!r)throw"invalid genome";const[o,l]=P(r,s);if(s.findterm)return await async function(e,t,n,s,r){const o={equals:[],startsWith:[],startsWord:[],includes:[]},i=decodeURIComponent(e.findterm).toUpperCase(),a=[];try{if("snp"==e.targetType){if(!s.queries?.snvindel?.allowSNPs)throw"this dataset does not support snp search";const e=await(0,D.SC)({byName:!0,lst:[i.toLowerCase()]},r);for(const t of e)a.push({type:"geneVariant",name:t.name,subtype:"snp",chr:t.chrom,start:t.chromStart,stop:t.chromEnd,alleles:t.alleles})}else{const t=(0,q.CG)({type:"geneVariant"},e.usecase).has("plot");if(s.mayGetMatchingGeneNames&&t&&await s.mayGetMatchingGeneNames(o,i,e),s.queries?.defaultBlock2GeneMode&&t)try{const e=(0,$.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,e.cohortStr,e.treeFilter,e.usecase);a.push(...l.map(G));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 u.update_image(s,n):s.getgroup?await u.getgroup(s,n):await u.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,f.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 a=[];if(o)try{a=r.q.getProfileFacilities(),n.send(a)}catch(e){n.send({error:e.message||e})}else n.send({error:"Requires sign in to access the sample data"})}(0,t,n,o,l);if("getAllSamples"==s.for)return async function(e,t,n,s){const r=i.i.canDisplaySampleIds(t,s);let o=[];r&&(o=Object.fromEntries(s.sampleId2Name));n.send(o)}(0,t,n,o);if("getAllSamplesByName"==s.for)return async function(e,t,n,s){if(!i.i.canDisplaySampleIds(t,s))return n.send({});if(s.queries?.singleCell?.samples?.get){const e=await s.queries.singleCell.samples.get(),t={};for(const n of e.samples)t[n.sample]=s.cohort.termdb.q.sampleName2id(n.sample);return void n.send(t)}{let t=s.sampleName2Id;if(e.filter){e.ds=s;const n=await(0,c.cf)(e.filter,e.ds,!0);t=new Map;for(const e of n)t.set(e.name,e.id)}n.send(Object.fromEntries(t))}}(s,t,n,o);if("DEanalysis"==s.for)return await async function(e,t,n){if(!n.queries?.rnaseqGeneCount)throw"not enabled by this dataset";const s=await n.queries.rnaseqGeneCount.get(e);t.send(s)}(s,n,o);throw"termdb: doesn't know what to do"}catch(e){n.send({error:e.message||e}),e.stack?console.log(e.stack):console.log(e)}}}function P(e,t){{const n=e.datasets[t.dslabel];if(n){if(n?.cohort?.termdb)return[n,n.cohort.termdb];throw".cohort.termdb not found on this dataset"}}if(!e.termdbs)throw"invalid dslabel";const n=e.termdbs[t.dslabel];if(!n)throw"invalid dslabel";if(!n.cohort)throw"ds.cohort missing for genome-level termdb";if(!n.cohort.termdb)throw"ds.cohort.termdb{} missing for a genome-level termdb";return[n,n.cohort.termdb]}function G(e){return JSON.parse(JSON.stringify(e))}},2974:(e,t,n)=>{"use strict";n.d(t,{Yu:()=>f,fZ:()=>d,gh:()=>p,te:()=>m});var s=n(1017),r=n.n(s),o=n(8907),i=n(5257),a=(n(9157),n(7147),n(7219),n(334)),l=n.n(a),c=n(3345),u=n(8599);async function f(e,t,n){try{return function(e,t,n){if(!t.cohort)throw"cohort missing from ds";if(!e.terms)throw"missing 'terms' parameter";e.ds=t,e.genome=n;for(const t of e.terms)t.term.name||(t.term=e.ds.cohort.termdb.q.termjsonByOneid(t.term.id)),t.q||console.log("do something??");if(e.currentGeneNames&&!Array.isArray(e.currentGeneNames))throw"currentGeneNames[] is not array";e.filter0&&"string"==typeof e.filter0&&(e.filter0=JSON.parse(e.filter0))}(e,t,n),await async function(e){const[t,n]=function(e){const t=[],n=[];for(const s of e){const e=s.term.type;"snplst"==e||"snplocus"==e||"geneVariant"==e?n.push(s):t.push(s)}return[t,n]}(e.terms),[s,r]=await async function(e,t){if(!t.length)return[{},{}];if(e.ds?.cohort?.db)return await p(e,t);if(e.ds?.variant2samples?.get)return await async function(e,t){const n={filter0:e.filter0,filterObj:e.filter,genome:e.genome,get:"samples",twLst:t,gdcUseCaseuuid:!0,isHierCluster:e.isHierCluster};e.rglst&&(n.rglst=e.rglst);if(e.currentGeneNames){n.geneTwLst=[];for(const t of e.currentGeneNames)n.geneTwLst.push({term:{name:t,type:"geneVariant"}})}const s=await e.ds.variant2samples.get(n),r={};for(const e of s.samples){const n={sample:e.sample_id};for(const s of t){const t=e[s.term.id];Array.isArray(t)&&null!=t[0]&&null!=t[0]?n[s.term.id]={key:t[0],value:t[0]}:null!=t&&null!=t&&(n[s.term.id]={key:t,value:t})}r[e.sample_id]=n}return[r,s.byTermId||{}]}(e,t);throw"unknown method for dictionary terms"}(e,t);if(t.length&&!Object.keys(s).length)return{samples:s,refs:{byTermId:r,bySampleId:{}}};const i=await async function(e,t){if(!t.find((e=>"snplst"==e.term.type||"snplocus"==e.term.type)))return;if(!e.filter)return;return new Set((await(0,o.cf)(e.filter,e.ds)).map((e=>e.id)))}(e,n);for(const o of n)if("geneVariant"==o.term.type){e.ds.cohort?.termdb?.getGeneAlias&&(r[o.term.name]=e.ds.cohort?.termdb?.getGeneAlias(e,o));const n=await e.ds.mayGetGeneVariantData(o,e);for(const[e,r]of n.entries())o.term.name in r&&(t.length||e in s||(s[e]={sample:e}),s[e]&&(s[e][o.term.name]=r[o.term.name]))}else{if("snplst"!=o.term.type&&"snplocus"!=o.term.type)throw"unknown type of non-dictionary term";{o.type=o.term.type;const e=new Map;await(0,u._)(o,e,!0);for(const[t,n]of e){if(i&&!i.has(t))continue;t in s||(s[t]={sample:t});const e={};for(const[t,s]of n.id2value)e[t]=s.value;s[t][o.term.id]=e}}}const a={};for(const t in s)e.ds.cohort?.termdb?.q?.id2sampleName?a[t]={label:e.ds.cohort.termdb.q.id2sampleName(Number(t))}:e.ds.__gdc?.caseid2submitter&&(a[t]={label:e.ds.__gdc.caseid2submitter.get(t)});return{samples:s,refs:{byTermId:r,bySampleId:a}}}(e)}catch(e){return e.stack&&console.log(e.stack),{error:e.message||e}}}async function d(e,t,n){e.ds=t;const s={};for(const t in e.filters){const n=e.filters[t],r=(await(0,o.cf)(n,e.ds)).map((e=>e.id));s[t]=Array.from(new Set(r))}n.send(s)}async function p(e,t){const n={},s={},r={},a=await(0,i.w)(e.filter,e.ds),l=a?a.values.slice():[],c=await Promise.all(t.map((async(t,n)=>{const i=await(0,o.Bi)(e,l,n,a,t);if(i.bins&&(s[t.term.id]={bins:i.bins}),i.events&&(s[t.term.id]={events:i.events}),t.term.values){const 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entries";if("logistic"==t){if([...new Set(e.data.map((e=>e[n.id])))].find((e=>![0,1].includes(e))))throw"non-0/1 outcome values found"}if("cox"==t){if([...new Set(e.data.map((e=>e[n.timeToEvent.eventId])))].find((e=>![0,1].includes(e))))throw"non-0/1 outcome event values found"}for(const t of e.independent)if("numeric"==t.rtype){if(t.refGrp)throw`reference group given for '${t.id}'`}else{if("factor"!=t.rtype)throw`variable rtype='${t.rtype}' not recognized`;{if(!t.refGrp)throw`reference group not given for '${t.id}'`;if("snplst"==t.type||"snplocus"==t.type)continue;const n=new Set(e.data.map((e=>e[t.id])));if(n.size<2)throw`fewer than 2 categories in data of variable='${t.id}'`;if(!n.has(t.refGrp))throw`reference group missing in data of variable='${t.id}'`}}}(s);const[r,a]=function(e){const t={},n={};if(t.outcome=e.outcome.id,n[e.outcome.id]="outcome",e.outcome.timeToEvent){const s=e.outcome.timeToEvent;t.outcome_time=s.timeId,n[s.timeId]="outcome_time",t.outcome_event=s.eventId,n[s.eventId]="outcome_event","age"==s.timeScale&&(t.outcome_agestart=s.agestartId,t.outcome_ageend=s.ageendId,n[s.agestartId]="outcome_agestart",n[s.ageendId]="outcome_ageend")}for(const[s,r]of e.independent.entries())t["id"+s+"_"]=r.id,n[r.id]="id"+s+"_";if(e.outcome.id=n[e.outcome.id],e.outcome.timeToEvent){const t=e.outcome.timeToEvent;t.timeId=n[t.timeId],t.eventId=n[t.eventId],"age"==t.timeScale&&(t.agestartId=n[t.agestartId],t.ageendId=n[t.ageendId])}for(const t of e.independent)if(t.id=n[t.id],t.interactions&&t.interactions.length>0)for(const[e,s]of t.interactions.entries())t.interactions[e]=n[s];for(const t of e.data)for(const e in t)t[n[e]]=t[e],delete t[e];return[t,n]}(s),l={resultLst:[]};return await Promise.all([A(s,r,e,l),C(e,n,s,l)]),console.log("benchmark:",_),l}catch(e){return e.stack&&console.log(e.stack),{error:e.message||e}}}function 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[]: "+r;e.q.restrictAncestry.pcs=o.pcs}}}function x(e,t,n){const s={id:e.id,name:e.term.name,type:"spline"==e.q.mode?"spline":"other",rtype:"continuous"==e.q.mode||"spline"==e.q.mode?"numeric":"factor"};if(e.interactions.length>0){s.interactions=[];for(const t of e.interactions){const e=n.independent.find((e=>e.id==t));if("snplst"==e.type)for(const t of e.highAFsnps.keys())s.interactions.push(t);else{if("snplocus"==e.type)continue;s.interactions.push(t)}}}"factor"===s.rtype&&(s.refGrp=e.refGrp),"spline"==e.q.mode&&(s.spline={knots:e.q.knots.map((e=>Number(e.value)))},n.independent.find((e=>"snplocus"==e.type))||(s.spline.plotfile=r().join(p().cachedir,Math.random().toString()+".png"))),t.push(s)}function N(e,t,n){for(const s of e.highAFsnps.keys()){const r={id:s,name:s,type:e.type};3==e.q.geneticModel?(r.rtype="factor",r.refGrp=e.q.snp2refGrp[s]):r.rtype="numeric";for(const t of n.independent)t.interactions.includes(e.id)&&(r.interactions||(r.interactions=[]),r.interactions.push(t.id));t.push(r)}if(e.q.restrictAncestry)for(const n of e.q.restrictAncestry.pcs.keys())t.push({id:n,name:n,type:"float",rtype:"numeric"})}function S(e){if("condition"==e.term.type){for(const t of e.q.groups)if(t.name!=e.refGrp)return t;throw"nonref group not found for logistic outcome"}if("predefined-groupset"==e.q.type){if(!e.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!Number.isInteger(e.q.groupsetting.predefined_groupset_idx))throw'outcome.q.predefined_groupset_idx not integer when q.type is "predefined-groupset"';if(!e.term.groupsetting)throw"outcome.term.groupsetting missing";const t=e.term.groupsetting.lst[e.q.groupsetting.predefined_groupset_idx];if(!t)throw"groupset not found by outcome.q.predefined_groupset_idx";const n=t.groups.find((t=>t.name!=e.refGrp));if(!n)throw"non-ref group not found for predefined-groupset";return n.name}if("custom-groupset"==e.q.type){if(!e.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!e.q.groupsetting.customset)throw"outcome.q.customset missing";const t=e.q.groupsetting.customset.groups.find((t=>t.name!=e.refGrp));if(!t)throw"non-ref group not found for custom-groupset";return t.name}if("values"==e.q.type){if(!e.term.values)throw"outcome.term.values{} missing";for(const t in e.term.values){const n=e.term.values[t];if(n.label!=e.refGrp)return n.label}throw"unknown nonref group from outcome.term.values"}if("custom-bin"==e.q.type){const t=e.q.lst.find((t=>t.label!=e.refGrp));if(!t)throw"non-ref bin is not found for custom-bin";return t.label}if("regular-bin"==e.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(e,t,n,s){v=(new Date).getTime();const o=r().join(p().cachedir,Math.random().toString()+".json");await m.Sf(o,JSON.stringify(e));const i=await(0,a.default)(r().join(p().binpath,"utils","regression.R"),[],[o]);c().unlink(o,(()=>{})),await async function(e,t,n,s,r){if(1!=t.length)throw"expected 1 json line in R output";const o=JSON.parse(t[0]),i=o.data;_["regression.R"]=o.benchmark;for(const t of i){const o={data:{sampleSize:t.data.sampleSize,eventCnt:t.data.eventCnt?t.data.eventCnt:null}};if(t.id){const e=n[t.id];o.id=e;const r=s.independent.find((e=>"snplocus"==e.type));if(!r)throw"snplocus term missing";o.AFstr=r.snpid2AFstr.get(e),o.data.headerRow=j(e,r)}const i=t.data;if(i.residuals&&(o.data.residuals=i.residuals,o.data.residuals.label="linear"==e.regressionType?"Residuals":"Deviance residuals"),"cox"==e.regressionType){if(i.coefficients.rows.length<1)throw"fewer than 1 row in coefficients table"}else if(i.coefficients.rows.length<2)throw"fewer than 2 rows in coefficients table";o.data.coefficients={header:i.coefficients.header,intercept:"cox"==e.regressionType?null:i.coefficients.rows.shift(),terms:{},interactions:[]};for(const e of i.coefficients.rows)if(-1!=e[0].indexOf(":")){const t={},[s,r]=e.shift().split(":"),[i,a]=e.shift().split(":");t.term1=n[s],t.category1=i,t.term2=n[r],t.category2=a,t.lst=e,o.data.coefficients.interactions.push(t)}else{const t=e.shift(),s=e.shift(),r=n[t];o.data.coefficients.terms[r]||(o.data.coefficients.terms[r]={}),s?(o.data.coefficients.terms[r].categories||(o.data.coefficients.terms[r].categories={}),o.data.coefficients.terms[r].categories[s]=e):o.data.coefficients.terms[r].fields=e}o.data.coefficients.label="Coefficients",o.data.type3={header:i.type3.header,terms:{},interactions:[]},"cox"!=e.regressionType&&(o.data.type3.intercept=i.type3.rows.shift());for(const e of i.type3.rows)if(-1!=e[0].indexOf(":")){const 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 e.independent)if(t.spline&&t.spline.plotfile){o.data.splinePlots||(o.data.splinePlots=[]);const e=t.spline.plotfile,n=await c().promises.readFile(e);o.data.splinePlots.push({src:"data:image/png;base64,"+new Buffer.from(n).toString("base64"),size:f()(e)}),c().unlink(e,(e=>{if(e)throw e}))}i.warnings&&(o.data.warnings=i.warnings);const a=s.independent.find((e=>"snplst"==e.type));if(a){if(a.lowAFsnps&&a.lowAFsnps.size){o.data.warnings||(o.data.warnings=[]);for(const e of a.lowAFsnps.keys())o.data.warnings.push(`${e}: effect allele frequency below cutoff, excluded from analysis`)}if(a.monomorphicLst&&a.monomorphicLst.length){o.data.warnings||(o.data.warnings=[]);for(const e of a.monomorphicLst)o.data.warnings.push(`${e}: monomorphic, excluded from analysis`)}}r.resultLst.push(o)}}(e,i,t,n,s),w=(new Date).getTime(),_.NodeJS.runRegression=(w-v)/1e3+" sec"}async function C(e,t,n,s){const o=e.independent.find((e=>"snplocus"==e.type));if(o){if(v=(new Date).getTime(),function(e,t){for(const n of e.monomorphicLst){const s=e.snpgt2count.get(n),r=[];for(const[e,t]of s)r.push(e+"="+t);const o={id:n,data:{headerRow:j(n,e)}};t.resultLst.push(o)}}(o,s),o.lowAFsnps.size)if("linear"==e.regressionType)await async function(e,t,n,s){const o=[],i=new Map;for(const[s,r]of e.lowAFsnps){let e=0,a=null,l=null;const c=[],u=[];for(const{sample:s,noOutcome:o}of t){if(o)continue;const t=n.data[e++].outcome;if(!Number.isFinite(t))continue;const i=r.samples.get(s);if(!i)continue;null==a?a=l=t:(a=Math.min(a,t),l=Math.max(l,t));const[f,d]=i.split("/");f==r.effAle||d==r.effAle?c.push(t):u.push(t)}o.push({group1_id:s+"_hasEffAllele",group1_values:c,group2_id:s+"_noEffAllele",group2_values:u}),i.set(s,{minv:a,maxv:l})}const l=r().join(p().cachedir,Math.random().toString()+".json");await m.Sf(l,JSON.stringify(o));const u=await(0,a.default)(r().join(p().binpath,"utils/wilcoxon.R"),[],[l]);c().unlink(l,(()=>{}));const f=JSON.parse(u);for(const t of f){const n=t.group1_id.replace("_hasEffAllele",""),r=t.group1_values,o=t.group2_values;let a;a=null==t.pvalue||"null"==t.pvalue?"NA":t.pvalue.toPrecision(4);const{minv:l,maxv:c}=i.get(n),u=m.JC(r.sort(((e,t)=>e-t)).map((e=>({value:e}))));u.label=`Carry ${0==e.q.alleleType?"minor":"alternative"} allele, n=${r.length}`;const f=m.JC(o.sort(((e,t)=>e-t)).map((e=>({value:e}))));f.label=`No ${0==e.q.alleleType?"minor":"alternative"} allele, n=${o.length}`;const d={id:n,AFstr:e.snpid2AFstr.get(n),data:{headerRow:j(n,e),wilcoxon:{pvalue:a,boxplots:{minv:l,maxv:c,hasEff:u,noEff:f}}}};s.resultLst.push(d)}}(o,t,n,s);else if("logistic"==e.regressionType)await async function(e,t,n,s){const r=[];let o=0;const i=new Map;for(const[s,a]of e.lowAFsnps){let e=0,l=0,c=0,u=0,f=0;for(const{sample:s,noOutcome:r}of t){if(r)continue;const t=n.data[f++],o="outcome"in t?t.outcome:t.outcome_event;if(0!=o&&1!=o)throw"outcome is not 0 or 1";const i=a.samples.get(s);if(!i)continue;const[d,p]=i.split("/"),m=a.effAle==d||a.effAle==p;0==o?m?l++:e++:m?u++:c++}i.set(o,s);const d={index:o,n1:u,n2:l,n3:c,n4:e};r.push(d),o++}const a=await(0,h.run_rust)("fisher",JSON.stringify({input:r}));for(const t of JSON.parse(a)){const n=i.get(t.index),{effAle:r}=e.lowAFsnps.get(n),o=t.p_value,a="chisq"===t.fisher_chisq,l={id:n,AFstr:e.snpid2AFstr.get(n),data:{headerRow:j(n,e),fisher:{isChi:a,pvalue:Number(o.toFixed(4)),rows:[["","Carry "+r+" allele","No "+r+" allele"],["Have event",t.n1,t.n3],["No event",t.n2,t.n4]]}}};s.resultLst.push(l)}}(o,t,n,s);else{if("cox"!=e.regressionType)throw"unknown regression type";await async function(e,t,n,s){const r={data:{}},o=new Set;for(const[s,i]of e.lowAFsnps){const e=[];let a=0;for(const{sample:s,noOutcome:r}of t){if(r)continue;const t=n.data[a++];if(0!==t.outcome_event&&1!==t.outcome_event)throw"d.outcome_event is not 0/1";if(!Number.isFinite(t.outcome_time))throw"d.outcome_time is not numeric";const o={time:t.outcome_time,event:t.outcome_event},l=i.samples.get(s);if(!l)continue;const[c,u]=l.split("/");o.series=i.effAle==c||i.effAle==u?"1":"2",e.push(o)}new Set(e.map((e=>e.series))).size<2?o.add(s):r.data[s]=e}const i=await(0,g.y)(r);let a;for(const[t,n]of e.lowAFsnps){if(o.has(t)){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[t].tests?.length)throw"must have a single test";const e=Number(i[t].tests[0].pvalue);if(!Number.isFinite(e))throw"invalid pvalue";a={pvalue:Number(e.toFixed(4)),ci_data:{[t]:i[t]}}}const n={id:t,AFstr:e.snpid2AFstr.get(t),data:{headerRow:j(t,e),cuminc:a}};s.resultLst.push(n)}}(o,t,n,s)}w=(new Date).getTime(),_.NodeJS.snplocusPostprocess=(w-v)/1e3+" sec"}}function j(e,t){const n=t.snpgt2count.get(e);if(!n)return{k:"Error",v:"Variant not found"};const s=[];for(const[e,t]of n)s.push(e+"="+t);const r={snpid:e,gtcounts:s};return t.monomorphicLst.includes(e)?r.monomorphic=!0:(r.effAle=t.highAFsnps.has(e)?t.highAFsnps.get(e).effAle:t.lowAFsnps.get(e).effAle,r.af=t.snpid2AFstr.get(e)),{k:"Variant:",v:r}}function T(e,t,n){if(e.q.restrictAncestry)for(const[n,s]of e.q.restrictAncestry.pcs)for(const[e,r]of s)t.has(e)&&t.get(e).id2value.set(n,{key:r,value:r})}async function M(e,t,n){const s=(await m.b5(r().join(p().cache_snpgt.dir,e.q.cacheid))).split("\n"),o=s[0].split("\t").slice(p().cache_snpgt.sampleColumn).map(Number);if(n)for(const e of o)t.set(e,{id2value:new Map});const i=o.map((e=>t.has(e))),a=new Map;for(let t=1;t<s.length;t++){const n=s[t].split("\t"),r=n[0],l={refAle:n[3],altAles:n[4].split(","),samples:new Map};e.q.snp2effAle?l.effAle=e.q.snp2effAle[r]:l.effAle=l.altAles[0],a.set(r,l);for(const[e,t]of o.entries()){if(!i[e])continue;const s=n[e+p().cache_snpgt.sampleColumn];s&&a.get(r).samples.set(t,s)}}"snplst"!=e.type||n||function(e,t,n,s){if(0==t.q.missingGenotype){for(const t of e.values()){let 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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");if(e.queries.singleCell)for(const e in 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'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 u(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)),u=n.n(c),f=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 function(e,t,n,s){if(!e.cacheid)throw"cacheid missing";if(u().cache_snpgt.fileNameRegexp.test(e.cacheid))throw"invalid cacheid";let r,o;if(n.track){if(r=n.track.vcf,!r)throw"ds.track.vcf missing"}else r=n.queries.snvindel.byrange._tk;if(e.filter){const t=new Set((await l.cf(e.filter,n)).map((e=>e.id)));if(0==t.size)throw"no samples from filter";o=r.samples.map((e=>t.has(e.name)))}else o=r.samples.map((e=>!0));const c=(await a.b5(i().join(u().cache_snpgt.dir,e.cacheid))).split("\n"),f=new Set,d=[];for(let e=1;e<c.length;e++){const t=c[e].split("\t"),n=t[0],s=t[3],i={},a={};for(let e=u().cache_snpgt.sampleColumn;e<t.length;e++){const n=t[e];if(!n)continue;if(!o[e-u().cache_snpgt.sampleColumn])continue;f.add(r.samples[e-u().cache_snpgt.sampleColumn].name),a[n]=1+(a[n]||0);const s=n.split("/");for(const e of s)i[e]=1+(i[e]||0)}const l=[];for(const e in i)l.push({allele:e,count:i[e],isRef:e==s});d.push({snpid:n,alleles:l,gt2count:a})}return{numOfSampleWithAnyValidGT:f.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(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: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(f,(()=>{}));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(u().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(","),u={snpid:c,chr:e.chr,pos:r};(0,f.H)(o,a,l,u,s[4],s[1]);for(const e of u.mlst)e.vcf_id&&(e.mname=e.vcf_id);g.snps.push(u);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(u().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?"<=":"<"} ${e.stop}`)}0!=n.length&&t.push("-i",n.join(" && "))}},8907:(e,t,n)=>{"use strict";n.d(t,{yT:()=>C,YG:()=>T,g5:()=>S,J4:()=>N,B9:()=>q,cf:()=>k,tt:()=>x,Bi:()=>A,ig:()=>M});var s={};n.r(s),n.d(s,{binary:()=>f,continuous:()=>l,cubicSpline:()=>c,discrete:()=>u});var r={};n.r(r),n.d(r,{groupset:()=>m,values:()=>d});var o={};n.r(o),n.d(o,{binary:()=>g,cox:()=>b,cuminc:()=>y,discrete:()=>h});var i=n(4048),a=n(5257);const l={getCTE(e,t,n,s,r,o,i){r.push(t.id);const a=C(t,s);return r.push(...a.values),{sql:`${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=? ${a.clause}\n\t\t\t)`,tablename:e}}},c=l,u={getCTE(e,t,n,s,r,o,i){r.push(t.id);const a=T(s,t,n,o,i),l=[],c=new Map;s.bin_size;for(const e of a)!("name"in e)&&e.label&&(e.name=e.label),c.set(e.name,e),l.push(`SELECT '${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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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}},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: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:u,request:{typeId:"HicdataRequest"},response:{typeId:"HicdataResponse"}},post:{alternativeFor:"get",init:u}}};function u(){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 u=["log(oe)"==e.matrixType?"oe":e.matrixType?e.matrixType:"observed",e.nmeth||"NONE",a,e.pos1,e.pos2,e.isfrag?"FRAG":"BP",e.resolution],f=(0,r.spawn)(l().hicstraw,u),d=i().createInterface({input:f.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])})),f.stderr.on("data",(e=>m.push(e))),f.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:()=>u});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 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(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 u=Number(j());let f=[];const d=1e5;if(8==l||7==l){let t=await q(e,u,d);const n=t.getInt32(0,!0);n>0&&(t=await q(e,u+n+4,d),f=await x(t,u+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);f=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=f,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 f("string");r.push(e),8==l||7==l?(e=await f("string"),c(4),c(8*await f("int32")),c(12*await f("int32"))):9==l&&(i+=4,e=await f("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&&u(),i+=e}async function u(){t=await q(e,n+i,d),n+=i,i=0}async function f(e){let n;if("string"==e){let e,s="";for(;i<t.byteLength&&0!=(e=t.getUint8(i++));)i>d&&await u(),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 u(),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 u=c.buffer;return u.buffer.slice(u.byteOffset,u.byteOffset+u.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},u=await(0,r.Yu)(c,o,i);if(u.error)throw u.error;const f=[];if("geneVariant"==e.type){const t=u.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)f.push({dt:e,classes:t})}else{const t=new Map;for(const n in u.samples){const s=u.samples[n][e.tid];s&&("key"in s&&t.set(s.key,1+(t.get(s.key)||0)))}for(const[n,s]of t)f.push({samplecount:s,key:n,label:u.refs?.byTermId?.[e.tid]?.events?.find((e=>e.event===n)).label||l?.values?.[n]?.label||n})}const d=(0,s.Tt)(l,u.refs?.byTermId?.[e.tid]?.bins||[],u.refs?.byTermId?.[e.tid]?.events,e.term1_q);d.length&&f.sort(((e,t)=>d.indexOf(e.label)-d.indexOf(t.label)));t.send({lst:f,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),u=n.n(c),f=n(4555),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(),f=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(u().cachedir,Math.random().toString()+".json");await l.Sf(o,JSON.stringify(s));const c=JSON.parse(await(0,a.default)(r().join(u().binpath,"utils/hclust.R"),[],[o]));await i().promises.unlink(o);const f=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 f){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);u().debugmode&&console.log("clustering done:",Date.now()-c,"ms");return{clustering:f,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(u().tpmasterdir)||(e.file=r().join(u().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,f.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 dataset name";if(!a.cohort.termdb)throw"invalid termdb object";await async function(e,t,n){const o=n.cohort.termdb.q.termjsonByOneid(e.tid);if(!o)throw"invalid termid";if("float"!=o.type&&"integer"!=o.type)throw"not numerical term";const i=await(0,s.J4)({ds:n,key:e.tid,filter:e.filter}),a=[];for(const{value:t}of i)o.values?.[t]?.uncomputable||"log"===e.settings?.violin?.unit&&0===t||a.push(t);t.send((0,r.Z)(a))}(o,n,a)}catch(e){n.send({error:e?.message||e}),e instanceof Error&&e.stack&&console.log(e)}}},request:{typeId:"getdescrstatsRequest"},response:{typeId:"getdescrstatsResponse"},examples:[{request:{body:{genome:"hg38-test",dslabel:"TermdbTest",embedder:"localhost",tid:"hrtavg",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}}}]}}}},5961:(e,t,n)=>{"use 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s=n(7147),r=n.n(s),o=n(1017),i=n.n(o),a=n(3345),l=n(334),c=n.n(l),u=n(4555);const f={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,u.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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cx="7" cy="12" r="7" fill="#b1b1b1"></circle><path d="M6.735557395310443e-16,-11A11,11 0 0,1 11,0L9,0A9,9 0 0,0 5.51091059616309e-16,-9Z" transform="translate(7,12)" fill="#858585" stroke="none"></path>',H={},W="S";H[W]={label:"Somatic",desc:"A variant found only in a tumor sample. 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of n)e&&(e.total=e.sum/e.count,delete e.sum,delete e.count);return n}async function cn(e,t){for(const e of t.regions)e.lines.length>0&&e.ntwidth>=$t&&(e.to_checkmismatch=!0,e.referenceseq=await mn(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),bn(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=fn(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=fn(o,r,e);if(!t||!t.qname)continue;const i=n.get(t.qname);i?(i.segments.push(t),i.x2=Math.max(i.x2,t.x2)):n.set(t.qname,{x1:Math.max(t.x1,r.x),x2:Math.min(t.x2,r.x+r.width),__tempscore:t.tempscore,segments:[t]})}}return[...n.values()]}function fn(e,t,n){const{sam_info:s,tempscore:r,ridx:o,keepallboxes:i,keepmatepos:a,keepunmappedread:l}=e,c=s.trim().split("\t");if(c.length<11)return;const u=c[0],f=c[1],d=Number.parseInt(c[3]),p=c[5],m=c[6],h=c[7],g=Number.parseInt(c[8]),y=c[9],b=c[10];if(Number.isNaN(d)||d<=0)return;const v=d-1,w={qname:u,segstart:v,segstart_original:v,segstop:v,boxes:[],forward:!(16&f),ridx:o,seq:y,qual:b,cigarstr:p,tlen:g,flag:f,tempscore:r};if(function(e,t,n,s,r,o){const i=e.flag;if(!(1&i))return;64&i?e.isfirst=!0:128&i&&(e.islast=!0);if("="!=t&&"*"!=t&&t!=s.chr)return e.rnext=t,void(e.pnext=n);if(8&i)return 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r.qual?t.rnext?e.fillStyle=rt:t.discord_orientation?e.fillStyle=gt:t.discord_wrong_insertsize?e.fillStyle=it:t.discord_unmapped2?e.fillStyle=mt:e.fillStyle=tt:o.to_printnt?e.fillStyle="white":t.rnext?e.fillStyle=rt:t.discord_orientation?e.fillStyle=gt:t.discord_wrong_insertsize?e.fillStyle=it:t.discord_unmapped2?e.fillStyle=mt:e.fillStyle=tt,i+r.len*o.ntwidth+zt<o.width&&i<o.width&&o.x<i+zt?e.fillRect(i,n,r.len*o.ntwidth+zt,s.stackheight):i+r.len*o.ntwidth+zt<o.width&&o.x>=i?e.fillRect(o.x,n,r.len*o.ntwidth+zt+i-o.x,s.stackheight):i+r.len*o.ntwidth+zt>=o.width&&o.x<i?e.fillRect(i,n,o.width-i,s.stackheight):i+r.len*o.ntwidth+zt>=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 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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=ht(r/Ut)),e.fillRect(a,n,o.ntwidth+zt,s.stackheight),a+=o.ntwidth}))}else t.discord_unmapped2&&(e.fillStyle=mt),e.fillRect(i,n,r.len*o.ntwidth+zt,s.stackheight);o.to_printnt&&(e.font=Math.min(o.ntwidth,s.stackheight-2)+"pt Arial")}else{"D"==r.opr?e.strokeStyle=qt:e.strokeStyle=s.stackheight<=2?xt:tt,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>Lt){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(Pt,Math.max(Gt,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=tt,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=tt,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=tt,e.fillText(r.len+" bp",(a+t)/2,n+s.stackheight/2)))}}}else e.fillStyle="white",i+r.len*o.ntwidth+zt<o.width&&o.x<i?e.fillRect(i,n,r.len*o.ntwidth+zt,s.stackheight):i+r.len*o.ntwidth+zt<o.width&&o.x>=i?e.fillRect(o.x,n,r.len*o.ntwidth+zt+i-o.x,s.stackheight):i+r.len*o.ntwidth+zt<=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+zt);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(_t,Math.max(kt,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 _n(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(_t,t.stackheight-2)+"pt Arial";for(const i of o){const o=r.x+r.scale(i.start);let a;i.qual?e.fillStyle=wt(i.qual.reduce(((e,t)=>e+t),0)/i.qual.length/Ut):e.fillStyle=bt,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 kn(e,t,n){const s=gn(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:'+st(s[t.cidx+n]/Ut)+'">'+e.seq[t.cidx+n]+"</td>")}const o=[];o.push('<li><span style="background:'+mt+';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 qn(e,t,n){const s=e.boxes[0].start,r=e.boxes[e.boxes.length-1],o=r.start+r.len,i=await mn(t,n.chr+":"+(s+1)+"-"+o),a=gn(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()?st:ut)+'">'+e.seq[t.cidx+n]+"</td>"):c.push('<td style="background:'+(r.toUpperCase()==o.toUpperCase()?st:ut)(a[t.cidx+n]/Ut)+'">'+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:'+pt(1)+'">'+e.seq[t.cidx+n]+"</td>"):c.push('<td style="background:'+pt(a[t.cidx+n]/Ut)+'">'+e.seq[t.cidx+n]+"</td>");else if(t.len>=Xt)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:'+bt+';background:white">'+e.seq[n]+"</td>"):c.push('<td style="color:'+bt+";background:"+st(a[n]/Ut)+'">'+e.seq[n]+"</td>")}let u=0,f=0,d=[],p=[],m=0;for(const t of e.boxes)u=f,f+=t.len,"S"==t.opr&&(m=1,d.push(u),p.push(f));const h=[];e.rnext&&h.push('<li>Next segment on <span style="background:'+rt+'">'+(n.nochr?"chr":"")+e.rnext+", "+e.pnext+"</span></li>"),e.discord_wrong_insertsize&&e.discord_orientation?h.push('<li><span style="background:'+it+';color:white">Wrong insert size</span> mate position: '+e.pnext+'</li><li><span style="background:'+gt+';color:white">Segments also having wrong orientation</span> '+e.discord_orientation_direction+"</li>"):e.discord_wrong_insertsize?h.push('<li><span style="background:'+it+';color:white">Wrong insert size</span> mate position: '+e.pnext+"</li>"):e.discord_orientation?h.push('<li><span style="background:'+gt+';color:white">Segments having wrong orientation</span> '+e.discord_orientation_direction+"</li>"):e.discord_unmapped2&&h.push('<li><span style="background:'+mt+';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:Xt};return 1==m&&(g.soft_starts=d,g.soft_stops=p),e.discord_unmapped2&&(g.unmapped_mate=!0),g}function xn(e){const t=Le().createHmac("md5",Yt),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 Nn(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 En(s.chr,s.start,s.stop,e.query.gdcFileUUID,xn(e),e);n.push({filesize:t})}return n}const Sn=r().features.bamCache||{},An=Sn.maxAge||72e5,Cn=Sn.maxSize||5e9,jn=Sn.checkWait||6e4;let Tn,Mn=0;function On(e=0){const t=Date.now()+e;if(Tn){if(Mn&&Mn<=t+5)return;clearTimeout(Tn),Tn=void 0}Mn=t,console.log(`will trigger mayDeleteCacheFiles() in ${e} ms`),Tn=setTimeout(In,e)}async function In(){console.log("checking for cached bam files to delete ...");try{const e=Date.now()-An,t=await m().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=g().join(r().cachedir_bam,l),c=await m().promises.stat(t);if(!c.isFile())continue;const u=c.mtimeMs;u<e?(await m().promises.unlink(t),a++,o+=c.size):(n.push({path:t,time:u,size:c.size}),s+=c.size)}if(n.sort(((e,t)=>t.time-e.time)),s>=Cn){const e=Date.now()-jn;for(const t of n){if(t.time>e)break;if(await m().promises.unlink(t.path),t.deleted=!0,a++,o+=t.size,s-=t.size,s<Cn)break}}console.log(`deleted ${a} of ${i} cached bam files (${o} bytes deleted, ${s} remaining)`),Tn=void 0,Mn=0;const l=s&&n.find((e=>!e.deleted));if(l){On(jn+Math.round(s>=Cn?0:Math.max(0,l.time+An-Date.now())))}}catch(e){console.error("Error in mayDeleteCacheFiles(): "+e)}}async function En(e,t,n,s,o,i){On(jn);const{host:a,headers:l}=en(i.query.__genomes).getHostHeaders(i.query);l.compression=!1;const c=g().join(r().cachedir_bam,o),u=g().join(a.rest,"/slicing/view/",s+"?region="+e+":"+t+"-"+n);try{const e=Math.round(Date.now()/1e3);if(await R.yE(c)){const e=b().stream(u,{method:"GET",headers:l}),t=m().createWriteStream(c);let n=0,s=!1;const o=new Ce.Transform({transform(e,t,o){n+=e.length,n>r().features.gdcBam.cacheMaxSize?(o(null,null),s=!0):o(null,e)}});if(await(0,je.pipeline)(e,o,t),s){try{await m().promises.stat(c),await m().promises.unlink(c)}catch(e){}throw`slice file size exceeds ${Ge(r().features.gdcBam.cacheMaxSize)}. Please reduce query region size and try again.`}if(await R.yE(c))throw"BAM file slice is not found after downloading"}else await m().promises.utimes(c,e,e);const t=c+".bai";if(await R.yE(t)){if(await async function(e){await R.UE({isbam:!0,args:["index",e],callback:()=>{}})}(c),await R.yE(t))throw"index file is missing after indexing"}else await m().promises.utimes(t,e,e);const n=await m().promises.stat(c);return(0,F.bplen)(n.size,!0)}catch(e){throw e.stack&&console.log(e.stack),"Error with BAM slicing: "+(e.message||e)}}r().features.bamCache&&On(jn);const Rn="Unannotated";function Fn(e){return e.file?e.file:e.file2?e.file2:e.url}function $n(e,t,n,s){const r=[];for(const o of e.samples)if(Number.isFinite(o.readcount)&&(o.readcount=Math.floor(o.readcount),!(o.readcount<=0||t.readcountCutoff&&o.readcount<t.readcountCutoff))){if(s.samples&&n.cohort&&n.cohort.annotation){const e=s.samples[o.i];if(!e)continue;const r=n.cohort.annotation[e];if(o.anno=r,t.cohortOnlyAttr&&n.cohort&&n.cohort.annotation){if(!r)continue;let e=!1;for(const n in t.cohortOnlyAttr){const s=r[n];if(s&&t.cohortOnlyAttr[n][s]){e=!0;break}}if(!e)continue}if(t.cohortHiddenAttr&&n.cohort&&n.cohort.annotation&&n.cohort.attributes){if(!r)continue;let e=!1;for(const s in t.cohortHiddenAttr){n.cohort.attributes.lst.find((e=>e.key==s)).isNumeric;const o=r[s];if(o){if(t.cohortHiddenAttr[s][o]){e=!0;break}}else if(t.cohortHiddenAttr[s][Rn]){e=!0;break}}if(e)continue}}if(o.events&&t.spliceEventPercentage){let n=!1;for(const s in o.events){if(!e.events[s])continue;const r=e.events[s].attrValue,i=t.spliceEventPercentage[r];if(!i)continue;const a=o.events[s].percentage;if(null!=a)if(">"==i.side){if(a<=i.value){n=!0;break}}else if(a>=i.value){n=!0;break}}if(n)continue}r.push(o)}return r}function Dn(e,...t){if(0==e.length)return 0;const n=e.sort(((e,t)=>e.readcount-t.readcount)),s=[];return 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Unknown variable type: "+e.type)),l.type||c++,as(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(cs[t.id]){t.bins=cs[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 {\n\t\t 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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=[],u&&e.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),f&&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,R.fk)(g().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=g().join(t.rest,"ssms"),n=await ds(e);if(n)throw`${e} returns error code: ${n}`}{const e=g().join(t.rest,"ssm_occurrences"),n=await ds(e);if(n)throw`${e} returns error code: ${n}`}{const e=g().join(t.rest,"cases"),n=await ds(e);if(n)throw`${e} returns error code: ${n}`}{const e=g().join(t.rest,"files"),n=await ds(e);if(n)throw`${e} returns error code: ${n}`}{const e=g().join(t.rest,"analysis/top_mutated_genes_by_project"),n=await ds(e);if(n)throw`${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: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\tprimary_site {buckets { doc_count, key }}\n\t\t\t\t}\n\t\t\t}\n\t\t}}",s=await b().post(e,{headers:t,body:JSON.stringify({query:n,variables:{}})});if(s.statusCode>399)return s.statusCode}catch(t){if(console.log(t),t.code)return t.code;throw"see above error from graphql API "+e}console.log("GDC GraphQL API okay: "+e,new Date-n,"ms")}(t.graphql,JSON.parse(JSON.stringify(n)));if(e)throw`${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# ${t.graphql}\n#\n##########################################`}}(e);try{await async function(e){if("stopGdcCacheAliquot"in r().features){if(!Number.isInteger(r().features.stopGdcCacheAliquot))return void console.log("GDC: sample IDs are not cached!");console.log("GDC: running limited sample ID caching")}else console.log("GDC: caching complete sample ID mapping");const t=1e3,n=await ps(e,1,0);if(!Number.isInteger(n))throw"totalCases not integer";const s=new Date;console.log("GDC: Start to cache sample IDs of",n,"cases...");for(let s=0;s<Math.ceil(n/t)&&(await ps(e,t,1e3*s),!(Number.isInteger(r().features.stopGdcCacheAliquot)&&s>=r().features.stopGdcCacheAliquot));s++);await async function(e){const{host:t,headers:n}=e.getHostHeaders(),s=`${t.geneExp}/gene_expression/availability`;try{const t=[...e.__gdc.caseIds],{body:r}=await(0,R.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 as(e){"case.diagnoses.age_at_diagnosis"!=e.id||(e.valueConversion={scaleFactor:1/365,fromUnit:"day",toUnit:"year"})}const ls={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}}},cs={"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 fs(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 ds(e){try{const t=new Date,n=await b()(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 ps(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 integers";r.push("size="+t),r.push("from="+n)}const{host:o,headers:i}=e.getHostHeaders(),{body:a}=await(0,R.fk)(o.rest+"/cases?"+r.join("&"),{headers:i});if(!Array.isArray(a?.data?.hits))throw"re.data.hits[] not array";for(const t of a.data.hits){const n=t.id;if(!n)throw"h.id (case uuid) missing";e.__gdc.caseIds.add(n);const s=t.submitter_id;if(!s)throw"h.submitter_id missing";if(e.__gdc.caseid2submitter.set(n,s),e.__gdc.map2caseid.cache.set(s,n),Array.isArray(t.samples))for(const s of t.samples){const t=s.submitter_id;if(!t)throw"sample.submitter_id missing";if(e.__gdc.map2caseid.cache.set(t,n),Array.isArray(s.portions))for(const r of s.portions)if(Array.isArray(r.analytes))for(const s of r.analytes)if(Array.isArray(s.aliquots))for(const r of s.aliquots){const s=r.aliquot_id;if(!s)throw"aliquot.aliquot_id missing";e.__gdc.aliquot2submitter.cache.set(s,t),e.__gdc.map2caseid.cache.set(s,n)}}}return a.data?.pagination?.total}var ms=n(4973),hs=n(3625),gs=n(478),ys=n(8907),bs=n(394);function vs(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 ws(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:g().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=g().join(r().tpmasterdir,o.dbfile);if(!await m().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 ${n}`),await m().copyFile(t,n)}await Os(e),n.send({status:"ok"})}catch(e){console.log(e),n.send({error:e.error||e})}}))}var _s=n(2188),ks=n(2974),qs=n(3795),xs=n(7934),Ns=n(5057),Ss=n(3677),As=n(4924),Cs=n(901);const js="Unannotated";async function Ts(e,t,n,s=null,o=null){for(const t in e.serverconfigFeatures||{})t in r().features?console.warn(`!!! NO OVERWRITING SERVERCONFIG.FEATURES.${t} (from ${e.label}) !!!`):r().features[t]=e.serverconfigFeatures[t];await Os(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)Ln.xq(e);else if(n.byrange.bcffile)n.byrange.bcffile=n.byrange.bcffile.startsWith(r().tpmasterdir)?n.byrange.bcffile:g().join(r().tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await Rs(e,t),n.byrange._tk?.samples.length||delete n.byrange._tk.samples,Es(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:g().join(r().tpmasterdir,n.byrange.chr2bcffile[e])};delete n.byrange.chr2bcffile,n.byrange.get=await Rs(e,t),n.byrange._tk.samples.length||delete n.byrange._tk.samples,Es(e,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";Ln.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";Ln.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:g().join(r().tpmasterdir,n.byrange.file),n.byrange.get=await async function(e,t){const n=e.queries.svfusion.byrange;if(n.file)await R.LC(n.file);else{if(!n.url)throw"file and url both missing on svfusion.byrange{}";n.dir=await R.d1(n.url,n.indexURL)}n.nochr=await R.Jy(n.file||n.url,null,t);{const e=await R.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=Fs(t),r=await(0,Cs.T)(t,n.samples,e);if(0==r?.size)return[];const o=new Map;for(const e of t.rglst)await R.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,u,f,d;try{l=JSON.parse(i[3])}catch(e){return}if(l.dt!=F.dtfusionrna&&l.dt!=F.dtsv)return;if(l.class=l.dt==F.dtsv?F.mclasssv:F.mclassfusionrna,t.hiddenmclass&&t.hiddenmclass.has(l.class))return;if(l.sample&&r&&!r.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:e.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: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,f,c,encodeURIComponent(u)].join(ms.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]:js;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:f,pairlstIdx:c,mname:u,pairlst:d,samples:[]}),m&&o.get(p).samples.push(m)}});return[...o.values()]}}(e,t),Es(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&&Ln.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:g().join(r().tpmasterdir,n.byrange.file),n.byrange.get=await async function(e,t){const n=e.queries.cnv.byrange;if(n.file)await R.LC(n.file);else{if(!n.url)throw"file and url both missing on cnv.byrange{}";n.dir=await R.d1(n.url,n.indexURL)}n.nochr=await R.Jy(n.file||n.url,null,t);{const e=await R.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=Fs(t),r=await(0,Cs.T)(t,n.samples,e);if(0==r?.size)return[];const o=[];for(const e of t.rglst)await R.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==F.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?F.mclasscnvgain:F.mclasscnvloss}else if(c.class!=F.mclasscnvgain&&c.class!=F.mclasscnvloss)return;if(c.ssm_id=[e.chr,c.start,c.stop,c.class].join(ms.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]:js;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 Es(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=g().join(r().tpmasterdir,e.file),await R.LC(e.file),e.nochr=await R.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,As.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=g().join(r().tpmasterdir,n.file);{const t=(await(s=n.file,new Promise(((e,t)=>{const n=[],r=[],o=(0,q.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 ${e.label}`)}var s;n.get=async function(t){if(2!=t.samplelst?.groups?.length)throw".samplelst.groups.length!=2";if(t.samplelst.groups[0].values?.length<1)throw"samplelst.groups[0].values.length<1";if(t.samplelst.groups[1].values?.length<1)throw"samplelst.groups[1].values.length<1";const s=[];let o=0;for(const r of t.samplelst.groups[0].values){if(!Number.isInteger(r.sampleId))continue;const t=e.cohort.termdb.q.id2sampleName(r.sampleId);t&&(n.allSampleSet.has(t)?s.push(t):o+=1)}const i=[];let a=0;for(const s of t.samplelst.groups[1].values){if(!Number.isInteger(s.sampleId))continue;const t=e.cohort.termdb.q.id2sampleName(s.sampleId);t&&(n.allSampleSet.has(t)?i.push(t):a+=1)}const l=s.length,c=i.length;if(l<1)throw"sample size of group1 < 1";if(c<1)throw"sample size of group2 < 1";const u={case:s.map((e=>e)).join(","),control:i.map((e=>e)).join(","),input_file:n.file,output_path:g().join(r().binpath,"utils")},f=8;let d;if(s.length<=f&&i.length<=f||"edgeR"==t.method){const e=new Date,n=(await async function(e,t){return new Promise(((n,s)=>{g().join(r().Rscript,e);const o=(0,q.spawn)(r().Rscript,[e]),i=[],a=[];try{Ce.Readable.from(t).pipe(o.stdin)}catch(t){o.kill();let n=t;a.length&&(n+=`killed edgeR('${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())}))}))}(g().join(r().binpath,"utils","edge.R"),JSON.stringify(u)),new Date);console.log("Time taken to run edgeR:",n-e,"ms"),t.method="edgeR";const s=g().join(r().binpath,"utils","r_output.txt");d=JSON.parse(m().readFileSync(s,"utf8")),m().unlink(s,(()=>{}))}else if("wilcoxon"==t.method){const e=new Date,n=await(0,we.run_rust)("DEanalysis",JSON.stringify(u)),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,we.run_rust)("DEanalysis",JSON.stringify(u)),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,Ss.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=g().join(r().tpmasterdir,n[s].folder,a.toString());try{await m().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 Gs(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=g().join(n[t].folder,o+".gz");try{return await m().promises.stat(g().join(r().tpmasterdir,i)),{path:i}}catch(e){return{}}}}}(e),await(0,xs.validate_query_singleCell)(e,t),await(0,Ns.validate_query_TopVariablyExpressedGenes)(e,t),await(0,ms.uK)(e),await function(e){if(!e.ssm2canonicalisoform)return;if(e.ssm2canonicalisoform.gdcapi)return void Ln.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 Bs(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 Bs(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 zs(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 zs(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==F.dtsnvindel?t.GT&&(s.value=t.GT,s.key=t.GT):e.dt!=F.dtfusionrna&&e.dt!=F.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,ys.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){Us(e,o.byOrigin[t],n,s,t,r)}else Us(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{}";Js(e,s)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";Js(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 ws(e,s,o)}function Ms(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 Os(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 is(e);else if(t?.dictionary?.dbFile)e.cohort.db={file:t.dictionary.dbFile},delete t.dictionary.dbFile,(0,bs.JV)(e);else{if(!e.cohort.db)throw"unknown method to initiate dictionary";(0,bs.JV)(e)}if(t.termid2totalsize2&&(t.termid2totalsize2.gdcapi,t.termid2totalsize2.get=async(n,s={},r=null)=>t.termid2totalsize2.gdcapi?await Ln.ws(n,s,r,e):await async function(e,t,n,s){const r=Is(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,Se.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,_s.wz)(e),await(0,ks.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";Ln.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.${e}`;const s=(0,q.spawnSync)(r().Rscript,["-e",`load('${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 Is(e,t){const n=[];if(e.filterObj&&n.push(e.filterObj),e.tid2value&&n.push((0,Cs.w)(e.tid2value,t)),0!=n.length)return 1==n.length?n[0]:(0,gs.xH)(n)}function Es(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 Rs(e,t){const n=e.queries.snvindel.byrange;if(n._tk.file)await R._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 R._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=Fs(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,Cs.T)(t,n._tk.samples,e);if(i){if(0==i.size)return[];o.push("-s",[...i].join(","))}t.variantFilter&&(0,qs.u)(t.variantFilter,o);const a=[];return await R.UE({isbcf:!0,args:o,dir:n._tk.dir,callback:r=>{const o=r.split("\t"),l=o[0],c=o[1],u=Number(o[2]),f=o[3],d=o[4].split(","),p=o[5],m={pos:u-1};(0,hs.H)(n._tk,f,d,m,p,l,t.isoform);for(const r of m.mlst)t.hiddenmclass&&t.hiddenmclass.has(r.class)||$s(r,t)||m.mlst.length>1&&t.variantFilter?.lst&&Ds(r,t)||(r.chr=(n._tk.nochr?"chr":"")+c,r.ssm_id=[r.chr,r.pos,r.ref,r.alt].join(ms.dq),n._tk?.samples?.length&&(Ls(n,r,o,t.addFormatValues,e,i,s),!r.samples)||a.push(r))}}),a}}function Fs(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 $s(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 Ds(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 Ls(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=Ps(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]:js;if(i[t].has(n)){e=!0;break}}if(e)continue}l.push(o)}}l.length&&(t.samples=l)}function Ps(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 Gs(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 u=[];for(const e in t.majorchr){const n=t.majorchr[e];l[e]=(0,ss.Z)().domain([0,n]).range([a*c,a*(c+n)]),c+=n,u.push({chr:e,chrLen:n,xStart:a*(c-n),xStop:a*c})}const f=(0,ss.Z)().domain([n.min,n.max]).range([r,0]),d=(0,N.createCanvas)(890*s,240*s),p=d.getContext("2d");s>1&&p.scale(s,s),g(n.max),g(0),g(n.min);const h=O().createInterface({input:m().createReadStream(e)});return new Promise(((e,s)=>{h.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 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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 zs(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 Bs(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 zs(t,n),r.rglst=[t],await e.queries.snvindel.byrange.get(r);throw"unknown queries.snvindel method"}function Js(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 Hs(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 Ws(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 Vs(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 Zs="Ancestry_PC_";async function Ks(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 Ys(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 Ys(n.file,t.PCcount)}}}}(e.cohort.termdb),await async function(e){if("scatterplots"in e)for(const t of e.scatterplots.plots){const e=g().join(r().tpmasterdir,t.file);await R.Ic(e)}}(e.cohort),(0,bs.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&&ws(e,t,s)}async function Xs(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]=g().join(r().tpmasterdir,e.chr2bcffile[t]);const n={file:e.chr2bcffile[t.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await R._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]=g().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 R._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;Vs(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=g().join(r().tpmasterdir,n.file)),await R.LC(n.file),n.nochr=await R.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 Ys(e,t){const n=new Map;for(let e=1;e<=t;e++)n.set(Zs+e,new Map);let s=0;for(const o of(await R.b5(g().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=Zs+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 Qs=n(9157);const er=n(334),tr="%CHROM\t%POS\t%ID\t%REF\t%ALT\t%QUAL\t%FILTER\t%INFO";async function nr(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 sr(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 ys.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=tr,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||(F.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 "+F.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 R.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]=$.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]=$.S(n,o);i=[];for(const t of s)e.m_is_filtered(t)||i.push(t)}else e.querymode.range_AFtest&&(i=function(e,t,n,s){const r=e.split("\t"),[o,i,a]=$.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(",")],u=[];for(const e of l){const n=or(r,e,c,t);if(rr(n)){if(u.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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s=l[n].split("\t"),r=s[0].split("_")[0],o=Number.parseInt(s[3]),a=Number.parseInt(s[4]);if(o>e.m.pos||a<e.m.pos+1)continue;const c=Number.parseFloat(s[7]),u={start:o,stop:a,strand:s[5],name:r,pvalue:c,score:Number.parseFloat(s[6]),logpvalue:-Math.log10(c)};t.fimo_motif.tf2attr&&(u.attr=t.fimo_motif.tf2attr[u.name]),i.push(u)}n(i)}))}))}function _r(e){!function(e){if(!e.sample2term)throw".sample2term missing";if(!e.terms)throw".terms[] missing";if(!e.config)throw".config{} missing"}(e);const t=function(e){const t=new Map;for(const n of e.sample2term.values())for(const e of n.keys())t.set(e,1+(t.get(e)||0));if(e.config.termidorder){const n=[];for(const s of e.config.termidorder){const e=t.get(s);null!=e&&n.push({id:s,samplecount:e})}return n}return[...t].sort(((e,t)=>t[1]-e[1])).map((e=>({id:e[0],samplecount:e[1]})))}(e),n=function(e,t){const n=[];for(const[s,r]of e.sample2term)t.find((e=>r.has(e.id)))&&n.push(s);return n}(e,t);return function(e,t,n){for(const[s,r]of t.entries()){const o=0==s?[{samples:n}]:t[s-1].blocks;r.blocks=kr(o,r.id,e)}}(e,t,n),function(e,t){for(const n of e){const e=t.terms.find((e=>e.id==n.id));n.name=e.name;for(const t of n.blocks)t.samplecount=t.samples.length,delete t.samples,t.value&&(t.color=e.values[t.value].color)}}(t,e),function(e){for(let t=e.length-1;t>=0;t--){const n=e[t];for(const e of n.blocks){let t=0;for(const n of e.children)t+=n.symbolwidth;const n=e.isgap?1:e.samplecount.toString().length;e.symbolwidth=Math.max(n,t)}}let t=0;for(const n of e[0].blocks){n.x=t;let e=t;for(const t of n.children)t.x=e,e+=t.symbolwidth;t+=n.symbolwidth}for(let t=1;t<e.length;t++)for(const n of e[t].blocks){let e=n.x;for(const t of n.children)t.x=e,e+=t.symbolwidth}for(const t of e)delete t.children}(t),t}function kr(e,t,n){const s=[];for(const r of e){const e=new Map,o=[];for(const s of r.samples){const r=n.sample2term.get(s);if(r){const n=r.get(t);null==n?o.push(s):(e.has(n)||e.set(n,[]),e.get(n).push(s))}else o.push(s)}const i=[...e].sort(((e,t)=>t[1].length-e[1].length));for(const e of i){const t={value:e[0],samples:e[1],children:[]};s.push(t),r.children&&r.children.push(t)}if(o.length){const e={isgap:!0,samples:o,children:[]};s.push(e),r.children&&r.children.push(e)}}return s}async function qr(e){const t=["futime\tfustat\trx"];for(const[n,s]of e.entries())for(const e of s.lst)t.push(e.serialtime+"\t"+e.censored+"\t"+n);const n=await(0,Qs.default)(g().join(r().binpath,"/utils/km.R"),t);return Number(n.join(""))}async function xr(e,t,n,s){const r=new Set(e.map((e=>e.name))),o=t.samplerule.set;let i,a;for(const e in n.queries){const t=n.queries[e];t.type==F.tkt.mdsvcf?i=t:t.type==F.tkt.mdssvcnv&&(a=t)}const l=new Set;if(o.cnv||o.loh||o.sv||o.fusion||o.itd){if(!a)throw"no svcnv found in ds.queries";if(s)return await Nr(a,r,t,!0);const e=await Nr(a,r,t);for(const t of e)l.add(t)}if(o.snvindel){if(!i)throw"no vcf found in ds.queries";for(const e of i.tracks)await Sr(i,e,r,l,t)}return e.filter((e=>l.has(e.name)))}async function Nr(e,t,n,s){const o=n.samplerule.set,i=e.url?await R.d1(e.url,e.indexURL):null,a=new Set,l=new Set,c=new Set;return await R.UE({args:[e.file?g().join(r().tpmasterdir,e.file):e.url,(e.nochr?o.chr.replace("chr",""):o.chr)+":"+o.start+"-"+(o.stop+1)],dir:i,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),i=Number.parseInt(n[2]),u=JSON.parse(n[3]);if(t.has(u.sample)){if(u.dt==F.dtcnv){if(!o.cnv)return;if(o.cnv.focalsizelimit&&i-r>=o.cnv.focalsizelimit)return;if(o.cnv.valuecutoff&&Math.abs(u.value)<o.cnv.valuecutoff)return;return s?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==F.dtloh){if(!o.loh)return;if(o.loh.focalsizelimit&&i-r>=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==F.dtsv){if(!o.sv)return;return c.add(u.sample),void o.samples_sv.add(u.sample)}if(u.dt==F.dtfusionrna){if(!o.fusion)return;return c.add(u.sample),void o.samples_fusion.add(u.sample)}if(u.dt==F.dtitd){if(!o.itd)return;return c.add(u.sample),void o.samples_itd.add(u.sample)}}}}),s?[a,l]:c}async function Sr(e,t,n,s,o){const i=o.samplerule.set,a=t.url?await R.d1(t.url,t.indexURL):null;await R.UE({args:[t.file?g().join(r().tpmasterdir,t.file):t.url,(t.nochr?i.chr.replace("chr",""):i.chr)+":"+i.start+"-"+(i.stop+1)],dir:a,callback:r=>{if(t.type==F.mdsvcftype.vcf){const[o,a,l]=$.S(r,{nochr:t.nochr,samples:t.samples,info:e.info,format:t.format});for(const e of a)if(e.sampledata&&!(i.snvindel.ref&&(e.ref!=i.snvindel.ref||e.alt!=i.snvindel.alt)||i.snvindel.hiddenclass&&(F.vcfcopymclass(e,{}),i.snvindel.hiddenclass[e.class])))for(const t of e.sampledata)n.has(t.sampleobj.name)&&(s.add(t.sampleobj.name),i.samples_snvindel.add(t.sampleobj.name))}}})}async function Ar(e,t,n){if(!n.queries)throw".queries{} missing from ds";let s;for(const e in 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t=Lr[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 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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==F.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 Yr(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 R.z5(t.snp.bigbedfile,e.chr,s.start,s.stop);for(const t of r){const s=Qr(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 R.mr(t.snp.bigbedfile,s);for(const t of e){const e=Qr(t);n.push(e)}}}return n}function Qr(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 eo(e,t,n){if(n.query.isoform&&Lr[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==F.tkt.junction&&(a.config.dsjunctiontk=e)}else a.lst=i;return a}function to(e,t){const n=[g().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,q.spawn)(Pr,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 no(e){if(!e.genome)return["no genome"];const t=Lr[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 so(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 go(i.file?g().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]=$.S(e,i);for(const e of n)F.basecolor[e.ref]&&F.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=mo(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),m().unlink(n,(()=>{})),m().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 oo(s,t,i):await ro(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 ro(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 R.UE({isbam:!0,args:s,dir:e.dir,callback:e=>r=e}),Number.parseInt(r)}function oo(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,q.spawn)(Gr,o,{cwd:e.dir}),a=(0,q.spawn)("cut",["-f1"],{cwd:e.dir}),l=(0,q.spawn)("sort",["-u"],{cwd:e.dir}),c=(0,q.spawn)("wc",["-l"],{cwd:e.dir});i.stdout.pipe(a.stdin),a.stdout.pipe(l.stdin),l.stdout.pipe(c.stdin);const u=[],f=[];c.stdout.on("data",(e=>u.push(e))),c.stderr.on("data",(e=>f.push(e))),c.on("close",(()=>{s(Number.parseInt(u.join("")))}))}))}function io(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,q.spawn)(Ur,["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});O().createInterface({input:i.stdout}).on("line",(e=>{if("#"==e[0])return;const n=po(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 ao(e,t,n,s,r,o){t.hideLOHwithCNVoverlap&&lo(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!=F.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)co(s,i,n,o,e,t);if(s)for(const r of s)if(r.dt!=F.dtsnvindel)console.log("unknown dt when grouping samples from vcf data: "+r.dt);else for(const s of r.sampledata)co(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!=F.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 lo(e){for(const[t,n]of e){const s=new Map,r=new Map,o=[];for(const e of n)e.dt!=F.dtloh?(e.dt==F.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 co(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 c=l.join(o.groupsamplebyattr.attrnamespacer);if(!n.has(c)){const e=[];for(const t of o.groupsamplebyattr.attrlst){const n=i[t.k];if(null==n)break;const s={k:t.k,kvalue:n};t.full&&(s.full=t.full,s.fullvalue=i[t.full]),e.push(s)}const t=[];for(const e of o.groupsamplebyattr.attrlst){const n=i[e.k];if(null==n)break;const s=(e.full?i[e.full]:null)||n;t.push(s)}n.set(c,{name:c,samples:[],attributes:e})}let u=!0;for(const s of n.get(c).samples)if(s.samplename==e){for(const e of t)s.items.push(e);u=!1;break}u&&n.get(c).samples.push({samplename:e,items:t})}function uo(e){return Number.isFinite(e.dna_mintotalreads)?Number.isFinite(e.rna_mintotalreads)?Number.isFinite(e.hetsnp_minbaf)?Number.isFinite(e.hetsnp_maxbaf)?Number.isFinite(e.rnapileup_q)?Number.isFinite(e.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 dna_mintotalreads"}function fo(e){const t=e+".pvalue";return new Promise(((n,s)=>{const o=(0,q.spawn)("Rscript",[g().join(r().binpath,"utils/binom.R"),e,t]);o.on("close",(()=>{n(t)})),o.on("error",(e=>{s(`cannot do binom test: ${e}`)})),o.stderr.on("data",(e=>{s(`cannot do binom test: ${e}`)}))}))}function po(e){const t=e.split("\t");if(t.length<8)return;const n={pos:Number.parseInt(t[1])-1},s=[t[3],...t[4].split(",")],r={};for(const e of t[7].split(";")){const t=e.split("=");r[t[0]]=t[1]}if(r.DP&&(n.DP=Number.parseInt(r.DP)),r.AD){n.allele2count={};const e=r.AD.split(",");for(const[t,r]of s.entries())n.allele2count[r]=Number.parseInt(e[t])}return n}function mo(e,t,n){const s=e.sampledata.find((e=>e.sampleobj.name==t));if(s){if(s.AD){const t=s.AD[e.ref]||0,r=s.AD[e.alt]||0,o={chr:e.chr,pos:e.pos,ref:e.ref,alt:e.alt,dnacount:{ref:t,alt:r}};return 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n=c.join("");!n||$r(n)?o({id:e.id,items:a}):i(n)}))}))))]}function ko(e,t,n,s){if(!e.chr)return["chr missing"];if(!Number.isInteger(e.start)||!Number.isInteger(e.stop))return["invalid start/stop coordinate"];if(e.stop-e.start>1e7)return["look range too big (>10Mb)"];if(null!=e.valuecutoff&&!Number.isFinite(e.valuecutoff))return["invalid value for valuecutoff"];if(null!=e.focalsizelimit&&!Number.isInteger(e.focalsizelimit))return["invalid value for focalsizelimit"];return[null,Promise.resolve().then((()=>{if(!n.file)return R.d1(n.url,n.indexURL)})).then((t=>new Promise(((o,i)=>{const a=[],l=(0,q.spawn)(Pr,[n.file?g().join(r().tpmasterdir,n.file):n.url,e.chr+":"+e.start+"-"+e.stop],{cwd:t});O().createInterface({input:l.stdout}).on("line",(t=>{const 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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)}})),Br.post(Jr+"/tkbedj",function(e){return async(t,n)=>{try{n.send(await async function(e,t){const[n,s,r]=R.ZX(e);if(n)throw n;let o,i,a,l,c;if(e.query.fileIsBigbed=await R.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 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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:$,returngmdata:_};if(0==S.length)return L.src=A.toDataURL(),L;const P=[];C.textAlign="center",C.textBaseline="middle";for(const[t,n]of S.entries()){const t=m&&n.category&&m[n.category]?m[n.category].color:n.color||u,s=n.canvas,r=(o+i)*(s.stack-1);n.genomicseq=(await R.Kf(x,n.chr+":"+(n.start+1)+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase();const l=(0,F.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 u=i.width/(i.stop-i.start),f=Math.min(o,3*u),d=f<8?null:f;let 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Ae(s,i,a);n.send(l)}catch(e){e.stack&&console.log(e.stack),n.send({error:e.message||e})}}}(Lr)),Br.all(Jr+"/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>Qt)throw`Slice range exceeds ${Ge(Qt)} 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,en(e),t.query),t.query.stream2download)return void await async function(e,t){const{host:n,headers:s}=en(e.query.__genomes).getHostHeaders(e.query);s.compression=!1;const o=g().join(n.rest,"/slicing/view/",e.query.gdcFileUUID+"?region="+e.query.gdcFilePosition);try{const e=b().stream(o,{method:"GET",headers:s});let n=0;e.on("data",(s=>{n+=s.length,n>r().features.gdcBam.streamMaxSize&&(e.destroy(),t.end())})),e.pipe(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=xn(t)}if(t.query.downloadgdc)return void n.send(await Nn(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=g().join(r().cachedir_bam,e.query.file),s=await m().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 sn(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 R.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=fn({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,we.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 kn(n,e,t.query)):r.push(await qn(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 sn(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 R.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(Bt,Jt*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 on(e,[i]),await an(i,e),void(e.regions[0].lines=i.lines)}await on(e,e.regions);for(const t of e.regions)await an(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=[],u=[],f=[];if(e.alleleAlreadyUpdated)o=e.leftflankseqs,i=e.rightflankseqs,u=e.refseqs,f=e.altseqs,a=e.refalleles,l=e.altalleles,c=e.ref_positions,0!=u[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="",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 R.Kf(e.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 t=(await R.Kf(e.genome,o.chr+":"+o.pos+"-"+o.pos)).split("\n").slice(1).join("").toUpperCase();i=t+o.ref,u=t,o.pos-=1}else u=o.alt,i=o.ref;const f=o.pos,d=i.toUpperCase(),p=u.toUpperCase();0==r?(t=f-s,n=f+i.length+1+s):(f-s<t&&(t=f-s),f+i.length+1+s>n&&(n=f+i.length+1+s)),a.push(d),l.push(p),c.push(f),r+=1}r=0;for(const s of e.variant){const d=(await R.Kf(e.genome,s.chr+":"+t+"-"+c[r])).split("\n").slice(1).join("").toUpperCase(),p=(await R.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),u.push(m),f.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:u[e],altseq:f[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,we.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:u,altseqs:f,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 R.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,we.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 u=[];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,u.push(t))}return{groups:u}}(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=pn(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 rn(n,r,e.partstack.start,e.partstack.stop,t.refseqs[0]):await rn(n,r,0,0,t.refseqs[0])}else if("support_no"==e.type){let r=t.leftflankseqs[0].length;s=e.partstack?await rn(n,r,e.partstack.start,e.partstack.stop):await rn(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 rn(n,o,e.partstack.start,e.partstack.stop,t.altseqs[r]):await rn(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=pn(s,e,r),await dn(s,e,r),await cn(r,e),hn(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,N.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)vn(a,t,s,e);_n(a,s,e,r),e.asPaired&&(o.count.t=r.length),e.variant&&(o.diff_scores_img=await 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s=[];w()(m().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 m().readFile(n,{encoding:"utf8"},((e,n)=>{e?t.send({error:"error reading file"}):t.send({text:n})}))})),Br.post(Jr+"/urltextfile",(async function(e,t){const n=e.query.url.replace(r().URL,`http://127.0.0.1:${r().port}`);try{const e=await b()(n);switch(e.statusCode){case 200:return void t.send({text:R.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})}})),Br.get(Jr+"/junction",(async function(e,t){try{const[n,s,o]=R.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 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s}(e.query,s,t)}t.send({lst:i})}catch(e){e.stack&&console.log(e.stack),t.send({error:e.message||e})}})),Br.post(Jr+"/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 R.d1(n.url,n.indexURL);else if(n.file)i.file=g().join(r().tpmasterdir,n.file);else{if(!n.file2)throw"no file or url given";i.file2=g().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 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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=Dn(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 R.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=$n(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(Dn(n,.5))})}return{lst:c}}(e,t,n);const s={};if(e.iscustom&&e.getsamples){const e=await R.ZD(Fn(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 R.UE({args:[Fn(n),s.chr+":"+s.start+"-"+s.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 t=u[4];let n;if("known"==t)n="canonical";else{if("novel"!=t)throw"unknown rnapeg type: "+t;n=Rn}if(e.infoFilter&&e.infoFilter.type&&e.infoFilter.type[n])return;const a={chr:s.chr,start:f,stop:d,info:{type:{lst:[{attrValue:n}]}}},l=[];for(let e=5;e<u.length;e++){const t=u[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=Dn(l,.05,.25,.5,.75,.95);a.medianReadCount=e[2],a.readcountBoxplot={percentile:e}}i.push(a)}else{u[3],u[4];if(!(f>=s.start&&f<=s.stop||d>=s.start&&d<=s.stop))return;o++;const c={chr:s.chr,start:f,stop:d,info:{type:{lst:[]}}},p=JSON.parse(u[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:Rn});if(e.infoFilter&&e.infoFilter.type)for(const t of c.info.type.lst)if(e.infoFilter.type[t.attrValue])return;const m=$n(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=Dn(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})}}}(Lr)),Br.post(Jr+"/mdscnv",(function(e,t){const[n,s,o,i]=no(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 "+F.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,q.spawn)(Pr,[i.file?g().join(r().tpmasterdir,i.file):i.url,t.chr+":"+t.start+"-"+t.stop],{cwd:i.usedir}),u=O().createInterface({input:a.stdout}),f=(t.stop-t.start)/t.width,d=[];for(let e=0;e<t.width;e++)d.push({positive:0,negative:0});u.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][zr]){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(t.start,r),p=Math.min(t.stop,i);let m,h;t.reverse?(m=Math.floor((t.stop-p)/f),h=Math.floor((t.stop-u)/f)):(m=Math.floor((u-t.start)/f),h=Math.floor((p-t.start)/f));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||$r(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,N.createCanvas)(s,e.query.gain.barheight+e.query.loss.barheight),a=r.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",s/2,e.query.gain.barheight),u.src=r.toDataURL(),void t.send(u);for(const e of n)for(const t of e)u.maxvalue=Math.max(u.maxvalue,t.positive,t.negative);const f=e.query.maxvalue||u.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(f,n.positive)/f),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(f,n.negative)/f),s=e.query.gain.barheight;a.fillRect(d,s,1,t)}d++}d+=e.query.regionspace}if(u.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([zr,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=me()((0,S.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}u.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++}u.hierarchySummary=n}}t.send(u)})).catch((e=>{t.send({error:e}),e.stack&&console.error(e.stack)}))})),Br.post(Jr+"/mdssvcnv",(async function(e,t){let n,s,o,i,a,l,c,u,f;if(e.query.iscustom){if(n=Lr[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=F.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=Lr[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=g().join(r().tpmasterdir,i);m().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==F.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=_r({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=Lr[e.query.genome],r=s.tracks.find((e=>e.__isgene)),i=(await ho(s,r,n.chr,n.start,n.stop)).get(n.name);if(!i)throw"no gene matching with "+n.name;const a={};await so(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 R.d1(i.url,i.indexURL),l=[];await R.UE({args:[i.file?g().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=bo(t.value,e),s[t.sample]=t}}else{n.sort(((e,t)=>e.value-t.value));for(const e of n)e.rank=bo(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 "+F.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&&(u={set:t,sample2group:n})}if(e.query.hiddensampleattr){f={};for(const t in e.query.hiddensampleattr)f[t]=new Set(e.query.hiddensampleattr[t])}if(o.url)try{o.dir=await R.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 u=new Promise(((l,u)=>{const f=[],d=(0,q.spawn)(Pr,[t.file?g().join(r().tpmasterdir,t.file):t.url,c.chr+":"+c.start+"-"+c.stop],{cwd:t.dir});O().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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e.cohort.sampleAttribute.attributes){e.cohort.sampleAttribute.attributes[t].clientnoshow||n.push(t)}for(const s of t.samplegroups)for(const r of s.samples){const s=e.cohort.annotation[r.samplename];if(s){const e={};let o=!1;for(const t of n){const n=s[t];null!=n&&(o=!0,e[t]=n)}o&&(t.sampleannotation[r.samplename]=e)}}}})(s,w),t.send(w)})),Br.post(Jr+"/mdsgenecount",(async function(e,t){try{const n=Lr[e.query.genome];if(!n)throw"invalid genome";if(!n.datasets)throw"no datasets from genome";const s=n.datasets[e.query.dslabel];if(!s)throw"invalid dataset";if(!s.gene2mutcount)throw"not supported on this dataset";if(!e.query.samples)throw".samples missing";let r,o;r=e.query.selectedMutTypes?e.query.selectedMutTypes.join("+"):"total",o=e.query.nGenes?e.query.nGenes:15;const i=`WITH\n\tfiltered AS (\n\t\tSELECT gene, ${r} AS total FROM genecount\n\t\tWHERE sample IN (${JSON.stringify(e.query.samples).replace(/[[\]\"]/g,"").split(",").map((e=>"'"+e+"'")).join(",")})\n\t)\n\tSELECT gene, 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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=cr}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:cr,label:"Unannotated"})}}catch(e){s.error=e.message||e,e.stack&&console.log(e.stack)}}(s,0,r,o),s.trigger_vcfbyrange&&(await nr(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 fr(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 R.UE({isbcf:!0,args:["query",i,"-r",o,"-f",tr+"\t%FORMAT\n"],dir:r.dir,callback:t=>{const[n,s,o]=$.S(t,r);for(const t of s)if(t.pos==e.m.pos&&t.ref==e.m.ref&&t.alt==e.m.alt)return void(a=t)}}),!a)throw"variant not found";const l=[],c=[],u=[];for(const t of a.sampledata){if(!t.genotype)continue;const n=-1!=t.genotype.indexOf(e.m.ref),s=-1!=t.genotype.indexOf(e.m.alt);n?s?c.push(t.sampleobj.name):l.push(t.sampleobj.name):s&&u.push(t.sampleobj.name)}const f=Math.random().toString();s.ssid=f,s.groups={};const d=[];if(l.length){const e="Homozygous reference";s.groups[e]={size:l.length},d.push(e+"\t"+l.join(","))}if(c.length){const e="Heterozygous";s.groups[e]={size:c.length},d.push(e+"\t"+c.join(","))}if(u.length){const e="Homozygous alternative";s.groups[e]={size:u.length},d.push(e+"\t"+u.join(","))}await R.Sf(g().join(er.cachedir_ssid,f),d.join("\n"))}(s,0,r,o),s.trigger_getvcfcsq&&await async function(e,t,n,s){const r=n.track.vcf;if(!r)throw"ds.track.vcf missing";if(!e.m)throw"q.m missing";const o=(r.nochr?e.m.chr.replace("chr",""):e.m.chr)+":"+(e.m.pos+1)+"-"+(e.m.pos+1),i=r.chr2bcffile[e.m.chr];if(!i)throw"chr not in chr2bcffile";await R.UE({isbcf:!0,args:["query",i,"-r",o,"-f",tr+"\\n"],dir:r.dir,callback:t=>{const[n,o,i]=$.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)}}}(Lr)),Br.post(Jr+"/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=Lr[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]=no(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 "+F.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 R.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,q.spawn)(Pr,[o.file?g().join(r().tpmasterdir,o.file):o.url,a.chr+":"+a.start+"-"+a.stop],{cwd:t}),u=O().createInterface({input:c.stdout}),f=new Map;u.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 f.has(r.gene)||f.set(r.gene,{chr:o,start:a,stop:l,allvalues:[]}),f.get(r.gene).thisvalue=r.value,void(r.ase&&(f.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),f.has(r.gene)||f.set(r.gene,{chr:o,start:a,stop:l,allvalues:[]}),f.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&&!$r(t)&&l({message:t}),n(f)}))})));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=bo(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})}))})),Br.post(Jr+"/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 R.d1(n.url,n.indexURL));s&&s.dsquery.url&&(s.dsquery.dir=await R.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 R.UE({args:[n.file?g().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 u=c.join(", ");if(!a.has(u)){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(u,t)}a.get(u).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}=R.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 u=[];for(const[e,t]of a)u.push({name:e,values:t.samples,attributes:t.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 e=u[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 f=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 R.UE({args:[t.dsquery.file?g().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(u[0]){const e=u[0].values;if(e.sort(((e,t)=>t.value-e.value)),f)for(const t of e){const e=f.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 u){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}=R.JC(e.values),c=[{isall:1,w1:n,w2:s,p25:r,p50:i,p75:a,out:l}];if(f){if(o.query.svcnv.usegain){const t=e.values.filter((e=>f.has(e.sample)&&f.get(e.sample).gain));if(t.length){const{w1:e,w2:n,p25:s,p50:r,p75:o,out:i}=R.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=>f.has(e.sample)&&f.get(e.sample).loss));if(t.length){const{w1:e,w2:n,p25:s,p50:r,p75:o,out:i}=R.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=>f.has(e.sample)&&f.get(e.sample).sv));if(t.length){const{w1:e,w2:n,p25:s,p50:r,p75:o,out:i}=R.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})}})(Lr)),Br.post(Jr+"/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=Lr[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]=no(n);if(e)throw e;s=t,o=r,i=a}const a=i.file?null:await R.d1(i.url,i.indexURL),l={};let c=!0;for(const e of n.genes){let t;await R.UE({args:[i.file?g().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})}})),Br.post(Jr+"/vcf",(async function(e,t){try{const[n,s,r]=R.ZX(e);if(n)throw n;const o=r?await R.d1(s,e.query.indexURL):null;if(!e.query.rglst)throw"rglst missing";const i=[];for(const t of e.query.rglst)await R.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})}})),Br.get(Jr+"/vcfheader",(async function(e,t){try{if(!e.query.genome)throw"genome missing";const n=Lr[e.query.genome];if(!n)throw"invalid genome";const[s,r,o]=R.ZX(e);if(s)throw s;const i=o?await R.d1(r,e.query.indexURL):null;t.send({metastr:(await R.ZD(r,i)).join("\n"),nochr:await R.Jy(r,i,n)})}catch(e){e.stack&&console.error(e.stack),t.send({error:e.message||e})}})),Br.post(Jr+"/translategm",(async function(e,t){try{const n=Lr[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 R.Kf(n,s.chr+":"+(s.start+1)+"-"+s.stop),o=F.fasta2gmframecheck(s,r);t.send({frame:o})}catch(e){t.send({error:e.message||e}),e.stack&&console.log(e.stack)}})),Br.post(Jr+"/samplematrix",(function(e,t){Promise.resolve().then((()=>{const t=Lr[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==F.tkt.mdsvcf){const s=e.query.querykey2tracks[t];s.type=F.mdsvcftype.vcf,n.queries[t]={type:F.tkt.mdsvcf,info:s.info,tracks:[s]}}else if(s.type==F.tkt.mdssvcnv)n.queries[t]=s;else{if(s.type!=F.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]=wo(t,n,e,s);if(o)throw"error with isgenevalue: "+o;r.push(i)}else if(t.iscnv){const[o,i]=_o(t,n,e,s);if(o)throw"error with iscnv: "+o;r.push(i)}else if(t.isloh){const[o,i]=ko(t,n,e,s);if(o)throw"error with isloh: "+o;r.push(i)}else if(t.isvcf){const[o,i]=Ao(t,n,e,s);if(o)throw"error with isvcf: "+o;r.push(i)}else if(t.isitd){const[o,i]=qo(t,n,e,s);if(o)throw"error with isitd: "+o;r.push(i)}else if(t.issvfusion){const[o,i]=xo(t,n,e,s);if(o)throw"error with issvfusion: "+o;r.push(i)}else if(t.issvcnv){const[o,i]=No(t,n,e,s);if(o)throw"error with issvcnv: "+o;r.push(i)}else if(t.ismutation){const[e,i]=So(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]=vo(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)}))})),Br.get(Jr+"/mdssamplescatterplot",(async function(e,t){try{const n=Lr[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})}})),Br.post(Jr+"/mdssamplesignature",(function(e,t){try{const n=e.query;if(!n.sample)throw".sample missing";const s=Lr[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})}})),Br.post(Jr+"/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 Ar(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 Ar(e,t,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:r.gene+" "+o.datatype+" from 1st quartile (n="+a+", value<"+u+")",lst:i.slice(0,a),isfirstquartile:!0},{name:r.gene+" "+o.datatype+" from 2nd quartile (n="+(l-a)+", "+u+"<=value<"+f+")",lst:i.slice(a,l)},{name:r.gene+" "+o.datatype+" from 3rd quartile (n="+(c-l)+", "+f+"<=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 xr(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 xr(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 u;c.length>1&&(u=await qr(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 qr([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 qr([t[0],t[e]]);return}if(e.samplerule.set.against4th){for(let e=0;e<3;e++)t[e].pvalue=await qr([t[e],t[3]]);return}}(s,c);for(const e of c)Cr(e),delete e.lst;const f={samplesets:c,pvalue:u};s.samplerule.set&&s.samplerule.set.mutation&&(f.count_snvindel=s.samplerule.set.samples_snvindel.size,f.count_cnv=s.samplerule.set.samples_cnv.size,f.count_loh=s.samplerule.set.samples_loh.size,f.count_sv=s.samplerule.set.samples_sv.size,f.count_fusion=s.samplerule.set.samples_fusion.size,f.count_itd=s.samplerule.set.samples_itd.size),n.send(f)}catch(e){e.stack&&console.error(e.stack),n.send({error:e.message||e})}}}(Lr)),Br.post(Jr+"/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 R.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 wr(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 wr(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,u=0;const f=[];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):u=Math.min(u,n.logpvaluediff),f.push(n));return{items:f,valuemin:u,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})}}}(Lr)),Br.all(Jr+"/termdb",ve.TO(Lr)),Br.all(Jr+"/termdb-barsql",Se.TO(Lr)),Br.post(Jr+"/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]=R.ZX({query:{file:e.textfile}});if(t)throw".textfile error: "+t;if(!s){if(await R.yE(n))throw"file not exist: "+e.textfile;if(await R.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?lr:hr;n=ar.Z(t),r={},o={}}else if(e.getpcd.category_customcolor){const t=ar.Z(hr);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]=R.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 R.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=_e.ZP(e((n-i)/(a-i)));s.set(t,Number.parseInt(yr(r.r,r.g,r.b),16))}}}var a,l;return new Promise(((i,a)=>{const l=[],c=O().createInterface({input:m().createReadStream(e.textfile)});let u=!0,f=0,d=0;c.on("line",(i=>{if(u)return void(u=!1);const a=i.split(e.delimiter),c=[];for(const t of e.getpcd.coord)c.push(a[t]),f=Math.max(f,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=_e.ZP(e.background_color),n=Number.parseInt(yr(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=_e.ZP(e.getpcd.gene_expression.color_no_exp);r=Number.parseInt(yr(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(f),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?ar.Z(lr):ar.Z(hr);if(!s.expfile)throw"getgeneboxplot.expfile missing";{const[e,t,n]=R.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 br(s),i=(s.nochr?s.chr.replace("chr",""):s.chr)+":"+s.start+"-"+s.stop;let a=0,l=0;await R.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 u=[],f=(d=ss.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=R.JC(t);delete n.out;const s=r(e);n.category=e,n.color=s,n.numberofcells=t.length,n.density=f(t),u.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(u.filter((e=>e.category==t.value))[0])}for(const t of e.getgeneboxplot.cat_values)t.order||p.push(u.filter((e=>e.category==t.value))[0]);for(const t of u){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=u;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]=R.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 br(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 R.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)}}}(Lr)),Br.post(Jr+"/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=pr.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("")}(),u=JSON.stringify(e.body),f=s?mr(n,l):r().cachedir_massSession;await m().promises.access(f).then((()=>!0)).catch((()=>!1))||m().mkdirSync(f,{recursive:!0}),await R.Sf(g().join(f,c),u),t.send({id:c})}catch(e){t.send({error:e.message||e})}})),Br.get(Jr+"/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?pr.i.getPayloadFromHeaderAuth(e,e.query.route):null,l=e.query.route?mr(e.query,a):r().cachedir_massSession,c=g().join(l,n);let u;try{u=(await m().promises.stat(c)).birthtime}catch(e){throw"invalid session"}const f=await R.b5(c),d=JSON.parse(f);if(e.query.route)return void t.send({state:d});const p=new Date,h=new Date(u),y=r().features.massSessionDuration||30,b=y-Math.round((p.getTime()-h.getTime())/864e5);t.send({state:d,sessionDaysLeft:b,massSessionDuration:y})}catch(e){t.send({error:e.message||e})}})),Br.delete(Jr+"/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?pr.i.getPayloadFromHeaderAuth(e,e.query.route):null;if(!a)throw"missing credentials";const l=e.query.route?mr(e.query,a):r().cachedir_massSession,c=[];for(const e of n){const t=g().join(l,e);m().unlink(t,(e=>{if(e)throw c.push(e),e}))}c.length||t.send({status:"ok"})}catch(e){t.send({error:e.message||e})}})),Br.get(Jr+"/sessionIds",(async function(e,t){try{const{filename:n,route:s,dslabel:r,embedder:o}=e.query,i=pr.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=mr(e.query,i);if(!await m().promises.access(a).then((()=>!0)).catch((()=>!1)))return void t.send({status:"ok",sessionIds:[]});const l=await m().promises.readdir(a);t.send({status:"ok",sessionIds:l})}catch(e){t.status(401),t.send({error:e.message||e})}})),Br.get(Jr+"/isoformbycoord",(async function(e,t){try{const n=Lr[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 R.UE({args:[g().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})}})),Br.post(Jr+"/ase",(async function(e,t){const n=e.query,s=3e6,o=5e5;try{const e=Lr[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=g().join(r().tpmasterdir,e.rnabamfile);else{if(!e.rnabamurl)throw"no file or url for rna bam";e.rnabamurl_dir=await R.d1(e.rnabamurl,e.rnabamindexURL||e.rnabamurl+".bai")}if(e.rnabam_nochr=await R.Dp(e.rnabamfile||e.rnabamurl,t,e.rnabamurl_dir),e.vcffile)e.vcffile=g().join(r().tpmasterdir,e.vcffile);else{if(!e.vcfurl)throw"no file or url for vcf";e.vcfurl_dir=await R.d1(e.vcfurl,e.vcfindexURL)}e.vcf_nochr=await R.Jy(e.vcffile||e.vcfurl,e.vcfurl_dir,t)}(n,e);const l=await ho(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 oo(e,n.chr,t):await ro(e,n.chr,t),t.fpkm=1e9*s/(n.rnabamtotalreads*t.exonlength)}else c.fpkmrangelimit=s;const[u,f,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),h=await async function(e,t,n,s,r){const o=await yo(e.vcffile||e.vcfurl,e.vcfurl_dir),[i,a,l,c]=$.e(o);if(c)throw c;const u={info:i,format:a,samples:l},f=await go(e.vcffile||e.vcfurl,(e.vcf_nochr?e.chr.replace("chr",""):e.chr)+":"+s+"-"+r,e.vcfurl_dir),d=[];for(const t of f||[]){const[n,s,r]=$.S(t,u);for(const t of s){if(!F.basecolor[t.ref]||!F.basecolor[t.alt])continue;if(!t.sampledata)continue;const n=mo(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,u,f);for(const e of h)e.rnacount={nocoverage:1};let y,b;p-d>=o?c.covplotrangelimit=o:(n.rnamax?y=n.rnamax:(y=await async function(e,t,n){let s=0;return await R.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=y),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,N.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,u=!1;n-t<=e.width?(u=!0,l=1,c=e.width/(n-t),a.lineWidth=c):(c=1,l=(n-t)/e.width);return await R.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 f=Number.parseInt(s[2]);if(!Number.isInteger(f))return;const d=e.rnabarheight*Math.min(f,r)/r,p=u?(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(),f>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:u,binpxw:c,binbpsize:l}}(n,d,p,h,y)),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,q.spawn)(Ur,["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});O().createInterface({input:c.stdout}).on("line",(e=>{if("#"==e[0])return;const n=po(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 u=0;for(const n of t)n.dnacount&&(n.pos<r||n.pos>o||(n.__x=e.width*(n.pos-r)/(o-r),u=Math.max(u,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)/u;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,h,0,0,d,p,b,y),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=g().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)=>{m().writeFile(t,n.join("\n")+"\n",(n=>{n&&s("cannot write"),e(t)}))}))}(n),o=await fo(s);await function(e,t){return new Promise(((n,s)=>{m().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),m().unlink(s,(()=>{})),m().unlink(o,(()=>{}))}(h,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}(h,l,n);let v=0;for(const e of h)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})}})),Br.post(Jr+"/bamnochr",(async function(e,t){const n=e.query;try{const e=Lr[n.genome];if(!e)throw"invalid genome";if(n.file)n.file=g().join(r().tpmasterdir,n.file);else{if(!n.url)throw"no bam file or url";n.url_dir=await R.d1(n.url,n.indexURL||n.url+".bai")}const s=await R.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})}})),Br.get(Jr+"/gene2canonicalisoform",(function(e,t){try{if(!e.query.gene)throw".gene missing";const n=Lr[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)}})),Br.get(Jr+"/ideogram",(function(e,t){try{const n=Lr[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})}}));R.lY,R.ZX;function jo(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 To(e){try{await m().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=x().spawnSync(r().Rscript,["-e",`suppressPackageStartupMessages(library("${t}"))`],{encoding:"utf8"});if(e.stderr.trim())throw e.stderr}const t=10;{const e=x().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.${t}`}{const e=x().execSync(r().bcftools+" -v",{encoding:"utf8"}).trim().split("\n"),[n,s]=e[0].split(" ");if("bcftools"!=n||!s)throw'cannot run "bcftools version"';const[o,i]=s.split(".");if("1"!=o)throw"bcftools not 1.*";if(Number(i)<t)throw`bcftools not >= 1.${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 Io("massSession"),e.cachedir_massSessionTrash=await Io("massSessionTrash"),e.cache_snpgt={dir:await Io("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},e.cachedir_bam=await Io("bam"),e.cachedir_genome=await Io("genome"),e.cachedir_ssid=await Io("ssid"),e.commonOverrides&&F.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=g().join(process.cwd(),t.file),s=require(m().existsSync(n)?n:t.file),r=s.default||s;if(Lr[t.name]=r,!r.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==r.genomefile||(r.genomefile=g().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&&Lr[e.defaultgenome]&&(Lr[e.defaultgenome].isdefault=!0);for(const t in Lr){const n=Lr[t];if(!n.majorchr)throw t+": majorchr missing";if(!n.defaultcoord)throw t+": defaultcoord missing";if(await R.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=R.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,bs.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 ${t}`).get().size)}if(n.termdbs)for(const e in n.termdbs)(0,bs.JV)(n.termdbs[e],Dr),console.log(`${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 R.LC(g().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=R.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=g().join(e.tpmasterdir,n.snp.bigbedfile),await R.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=g().join(e.tpmasterdir,n.fimo_motif.db),n.fimo_motif.annotationfile){const[t,s]=jo(m().readFileSync(g().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 R.LC(g().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=g().join(e.tpmasterdir,r.file);try{await R.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=g().join(process.cwd(),e.jsfile),r=require(m().existsSync(s)?s:e.jsfile),o="function"==typeof r?r(F):"function"==typeof r?.default?r.default(F):r.default||r;if(vs(o,e),o.noHandleOnClient=e.noHandleOnClient,o.label=e.name,o.genomename=t,n.datasets[o.label]=o,o.isMds3)try{await Ts(o,n,0,Br,Jr)}catch(e){throw e.stack&&console.log(e.stack),"Error with mds3 dataset "+o.label+": "+e}else if(o.isMds)try{await Ro(o,n,e)}catch(e){throw"Error with mds dataset "+o.label+": "+e}else Oo(o,n)}Mo(),delete n.rawdslst}}}async function Mo(){const e=await m().promises.readdir(r().cachedir_massSession);try{e.forEach((async e=>{const t=(await m().promises.stat(g().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 m().promises.copyFile(g().join(r().cachedir_massSession,e),g().join(r().cachedir_massSessionTrash,e)),await m().promises.unlink(g().join(r().cachedir_massSession,e)),console.log("File deleted: ",e,t))}))}catch(e){throw`Error: ${e}`}}function Oo(e,t){if(e.dbfile)try{console.log("Connecting",e.dbfile),e.newconn=R.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=m().readFileSync(g().join(r().tpmasterdir,n.file),"utf8").trim();if(!s)throw n.file+" is empty for "+e.genomename+"."+e.label;t=[...t,...Q(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=Eo(n,e,t);if(s)throw'Error parsing a query in "'+e.label+'": '+s}if(e.vcfinfofilter){const t=F.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 Io(e){const t=g().join(r().cachedir,e);try{await m().promises.stat(t)}catch(e){if("ENOENT"!=e.code)throw"error stating dir";try{await m().promises.mkdir(t)}catch(e){throw"cannot make dir"}}return t}function Eo(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=x().execSync(Pr+" -H "+g().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]=$.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=x().execSync(Pr+" -l "+g().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=F.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 Ro(e,t,n){if((e.isMds2||e.isMds3||e.isMds)&&vs(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 m().readFileSync(g().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=R.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 m().readFileSync(g().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(!F.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 m().readFileSync(g().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 Ks(e,Br,Jr),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]=jo(m().readFileSync(g().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!=F.tkt.mdssvcnv)throw"type is not "+F.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]=jo(m().readFileSync(g().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 "+s;if(r.type==F.tkt.mdsjunction){const n=$o(r,e,t);if(n)throw s+" (mdsjunction) error: "+n}else if(r.type==F.tkt.mdscnv){const n=Po(r,e,t);if(n)throw s+" (mdscnv) error: "+n}else if(r.type==F.tkt.mdssvcnv){const n=Go(r,e,t);if(n)throw s+" (svcnv) error: "+n}else{if(r.type!=F.tkt.mdsvcf)throw"unknown track type for a query: "+r.type+" "+s;{const n=await zo(r,e,t);if(n)throw s+" (vcf) error: "+n}}Fo(r,e)}else{if(!r.isgenenumeric)throw"unknown type of query from "+s;{const n=Uo(r,e,t);if(n)throw s+" (genenumeric) error: "+n}}}if(e.track&&await Xs(e,t),e.annotationsampleset2matrix){if(!e.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!e.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!e.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!e.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!e.annotationsampleset2matrix.groups)throw".groups{} 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 Fo(e,t){if(e.groupsamplebyattr){e.groupsamplebyattr.key2group=new Map;for(const n in t.cohort.annotation)co(n,[],e.groupsamplebyattr.key2group,[],t,e)}}function $o(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]=Co(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=x().execSync(Pr+" -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=Do(e.samples,t),e.hierarchySummary=Lo(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=x().execSync(Pr+" -l "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=F.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 Do(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 Lo(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,S.N)(n,e.levels),r=me()(t);r.sum((e=>e.value));const o={};r.eachBefore((e=>{o[e.id]=e.value})),s[e.name]=o}return s}function Po(e,t,n){let s;if(e.file){const[t,n]=Co(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=x().execSync(Pr+" -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=Do(e.samples,t),e.hierarchySummary=Lo(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=x().execSync(Pr+" -l "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=F.contigNameNoChr(n,t.split("\n"))}console.log("("+e.type+") "+e.name+": "+(e.samples?e.samples.length:"no")+" samples, "+(e.nochr?'no "chr"':'has "chr"'))}function Go(e,t,n){let s;if(e.file){const[t,n]=Co(e.file);if(t)return"tabix file error: "+t;s=n}else{if(!e.url)return"no file or url given for (svcnv) "+e.name;s=e.url}const r={encoding:"utf8"};const o=x().execSync(Pr+" -H "+s,r).trim();if(o){const n=new Set;for(const e of o.split("\n"))for(const t of e.split(" ").slice(1))n.add(t);if(0==n.size)return"no samples from the header line";if(e.samples=[...n],t.cohort&&t.cohort.annotation){const n=new Set;for(const s of e.samples)t.cohort.annotation[s]||n.add(s);n.size&&console.log("mdssvcnv unannotated samples: "+(e.noprintunannotatedsamples?n.size:[...n].join(" ")))}}{const t=x().execSync(Pr+" -l "+s,r).trim();if(!t)return"no chromosomes found";e.nochr=F.contigNameNoChr(n,t.split("\n"))}if(e.expressionrank_querykey){const 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!=F.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 groupsamplebyattr.attrlst[]";t.cohort.sampleAttribute.attributes[n.k]||(t.cohort.sampleAttribute.attributes[n.k]={label:n.label||n.k})}if(e.groupsamplebyattr.sortgroupby){if(!e.groupsamplebyattr.sortgroupby.key)return".key missing from .sortgroupby";if(!e.groupsamplebyattr.sortgroupby.order)return".order[] missing from .sortgroupby";if(!Array.isArray(e.groupsamplebyattr.sortgroupby.order))return".order must be an array"}e.groupsamplebyattr.attrnamespacer||(e.groupsamplebyattr.attrnamespacer=", ")}console.log("("+e.type+") "+e.name+": "+(e.samples?e.samples.length:"no")+" samples, "+(e.nochr?'no "chr"':'has "chr"'))}function Uo(e,t,n){if(!e.datatype)return"datatype missing";if(e.viewrangeupperlimit&&Number.isNaN(e.viewrangeupperlimit))return"invalid value for viewrangeupperlimit";let s;if(!e.file)return"file missing";{const[t,n]=Co(e.file);if(t)return"tabix file error: "+t;s=n}const r={cwd:null,encoding:"utf8"};{const t=x().execSync(Pr+" -H "+s,r).trim();if(!t)return"no header line 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R.ZD(o,s.cwd);if(0==t.length)return"no meta/header lines for "+o;const[n,r,i,a]=$.e(t);if(a)return"error parsing vcf meta for "+o+": "+a.join("\n");if(0==i.length)return"vcf file has no sample: "+o;for(const t in n)e.info[t]=n[t];if(s.format=r,s.samplenameconvert){if("function"!=typeof s.samplenameconvert)return".samplenameconvert must be function";for(const e of i)e.name=s.samplenameconvert(e.name)}s.samples=i}if(t.cohort&&t.cohort.annotation){const e=[];for(const n of s.samples)t.cohort.annotation[n.name]||e.push(n.name);e.length&&console.log(t.label+": VCF "+s.file+" has unannotated samples: "+e.join(","))}{const e=[];if(await R.UE({args:["-l",o],dir:s.cwd,callback:t=>{e.push(t)}}),0==e.length)return"no chr from "+o;s.nochr=F.contigNameNoChr(n,e)}console.log("("+e.type+") "+o+": "+s.samples.length+" samples, "+(s.nochr?"no chr":"has chr"))}if(e.singlesamples){if(!e.singlesamples.tablefile)return".singlesamples.tablefile missing for the VCF query";e.singlesamples.samples={};let t=0;for(const n of m().readFileSync(g().join(r().tpmasterdir,e.singlesamples.tablefile),{encoding:"utf8"}).trim().split("\n")){if(!n)continue;if("#"==n[0])continue;const s=n.split("\t");s[0]&&s[1]&&(e.singlesamples.samples[s[0]]=s[1],t++)}console.log(t+" single-sample VCF files")}}},6191:(e,t,n)=>{"use strict";n.d(t,{i:()=>y});var s=n(7147),r=n(1017),o=n.n(r),i=n(9344),a=n.n(i),l=n(8088);async function c(e,t){!function(e){for(const t in e){const n=e[t];if("login"==n.type){if(n.embedders)throw"unexpected 'embedders' property";n["*"]={"*":{type:"basic",password:n.password,secret:n.secret}},delete n.type,delete n.password}else if("jwt"==n.type){for(const e in n.embedders)n.termdb={[e]:Object.assign({type:n.type},n.embedders[e])},n.headerKey&&(n.termdb[e].headerKey=n.headerKey);delete n.type,delete n.embedders,delete n.headerKey}else if(n.type)throw`unknown legacy credentials type='${n.type}'`}}(e);const n="secrets";if("string"==typeof e[n]){const t=await 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e=t[s.term.id];Number.isFinite(e)&&(t[s.term.id]=Z(o,e))}}else if("continuous"!=s.q.mode)throw"mayApplyBinning: unknown numeric q.mode";return n}function Z(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 K(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 X(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(O(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"],i=new Map;for(const e of r){const t=e.term.id.replace(/^case\./,"");o.push(t),i.set(t,e.term.id)}const{host:a,headers:l}=n.getHostHeaders(e),c=await C.post(T().join(a.rest,"cases"),{headers:l,json:{size:n.__gdc.casesWithExpData.size,fields:o.join(","),case_filters:s.content.length?s:void 0}}).json();if(!Array.isArray(c?.data?.hits))throw"re.data.hits[] not array";const u=[];for(const e of c.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)W(t,e,n);u.push(t)}const f=V(u,r);return{byTermId:f,samples:u}}(e,t,n);if(K(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 i={size:1e4,fields:o.join(",")};z(e,n),Object.assign(i,le.filters(e,n));const{host:a,headers:l}=n.getHostHeaders(e),c=await C.post(T().join(a.rest,le.endpoint),{headers:l,json:i}).json();if(delete e.isoforms,!Array.isArray(c?.data?.hits))throw"variant2samples re.data.hits is not array for query";const u=[];for(const t of c.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(B(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)W(s,t.case,e);Y(t.case,s),Q(s,n),u.push(s)}const f=V(u,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)u.push(t)}const d=new Map;for(const e of u)(0,M.z9)([e],d,e.ssm_id);return{byTermId:f,samples:[...d.values()]}}function Y(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 Q(e,t){const n=e["case.project.project_id"];n&&(e.caseIsOpenAccess=t.__gdc.gdcOpenProjects?.has(n))}async function ee(e,t,n,s){K(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),i=function(e,t){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};ce(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(O(e.filterObj));return n}(t,s),{host:a,headers:l}=s.getHostHeaders(t),c=["data","explore","cases","aggregations"];let u=(await C.post(a.graphql,{headers:l,json:{query:o,variables:i}}).json())[c[0]];for(let e=1;e<c.length;e++)if(u=u[c[e]],!u)throw`.${c[e]} missing from data structure of termid2totalsize2 for query :${o} and filter: ${filter}`;for(const e of r){if("categorical"==e.type&&!Array.isArray(u[e.path].buckets))throw c.join(".")+" not array for query :"+o+" and filter: "+filter;if(("integer"==e.type||"float"==e.type)&&"object"!=typeof u[e.path].stats)throw c.join(".")+" not object for query :"+o+" and filter: "+filter}const f=new Map;for(const e of r)if("categorical"==e.type){const t=u[e.path].buckets,n=[];for(const e of t)n.push([e.key.replace(".","__"),e.doc_count]);f.set(e.id,n)}else if("integer"==e.type||"float"==e.type){const t=u[e.path].stats.count;f.set(e.id,{total:t})}return n?[f,n]:f}function te(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 C(s.rest+"/ssms/"+n.ssm_id+"?fields="+t.join(","),{headers:r}).json();if(!o.data||!o.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(o.data.consequence))throw".data.consequence not array";return o.data.consequence.map((e=>e.transcript))}}function ne(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 se(t.sample,e)));return await async function(e,t,n){const r={mlst:[],dt2total:[]};{const{host:n,headers:o}=t.getHostHeaders(e),i=await C.post(T().join(n.rest,ie.endpoint),{headers:o,json:{size:1e4,fields:ie.fields.join(","),filters:ie.filters(e).filters}}).json();if(!Number.isInteger(i.data?.pagination?.total))throw"re.data.pagination.total not integer";if(!Array.isArray(i.data?.hits))throw"re.data.hits[] not array";i.data.hits.length<i.data.pagination.total&&r.dt2total.push({dt:1,total:i.data.pagination.total});for(const e of i.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 C.post(T().join(n.rest,"files"),{headers:r,json:{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)}}).json();if(!Array.isArray(o.data.hits))throw"re.data.hits[] not array";let i,a,l;for(const e of o.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;i=e.file_id;continue}if("WGS"==e.experimental_strategy){if(!e.file_id)continue;if("Copy Number Segment"!=e.data_type)continue;a=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;l=e.file_id}const c=[];if(a){const e=(await C(T().join(n.rest,"data",a),{headers:r}).text()).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)||(c.push(a),r>0&&0==i&&o>0&&c.push({dt:s.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(i){const e=(await C(T().join(n.rest,"data",i),{headers:r}).text()).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)||c.push(r)}}if(l)try{const e=(await C(T().join(n.rest,"data",l),{headers:r}).text()).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)&&(H(r,n[6]),c.push(r))}}catch(e){}return c}(e,t);r.mlst.push(...n)}return r}(t,e)}}async function se(e,t){const{host:n,headers:s}=t.getHostHeaders(q),r=await C.post(T().join(n.rest,"cases"),{headers:s,json:{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]}}]}}}).json();console.log(r);for(const e of r.data.hits)if(e.case_id)return e.case_id;throw"cannot convert to case_id (uuid)"}function re(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:["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),i=await C.post(T().join(r.rest,"files"),{headers:o,json:s}).json();if(!Number.isInteger(i.data?.pagination?.total))throw"re.data.pagination.total is not int";if(!Array.isArray(i.data?.hits))throw"re.data.hits[] not array";const a=new Map;for(const e of i.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(a.has(s)||a.set(s,{sample:s,"case.primary_site":n.primary_site,"case.disease_type":n.disease_type,"case.project.project_id":n.project?.project_id,experiments:[]}),!n.samples?.[0])throw"h.cases[0].samples[0] missing";a.get(s).experiments.push({experimentID:t,sampleName:n.samples[0].submitter_id,sampleType:n.samples[0].sample_type})}return{samples:[...a.values()]}}}function oe(e,t){e.queries.singleCell.data.get=async t=>{const{host:n,headers:s}=e.getHostHeaders(t),r=(await C(T().join(n.rest,"data",t.sample),{headers:s}).text()).trim().split("\n"),o={name:"UMAP",cells:[],colorBy:"Cluster"},i={name:"TSNE",cells:[],colorBy:"Cluster"},a={name:"PCA",cells:[],colorBy:"Cluster"},l={id:"cluster",name:"Seurat cluster",type:"categorical",values:{}},c={[l.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 u=n[3];if(!u)throw"seuratCluster missing from a line";l.values[u]={label:"Cluster "+u},c[l.id][s]=`Cluster ${u}`;const f=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(f))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 ${u}`;o.cells.push({cellId:s,x:f,y:d,category:y}),i.cells.push({cellId:s,x:p,y:m,category:y}),a.cells.push({cellId:s,x:h,y:g,category:y})}return{plots:[i,o,a],terms:[l],tid2cellvalue:c}}}const ie={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],ae(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(O(e.filterObj)),t}};function ae(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 le={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],ae(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(O(e.filterObj)),ce(e.tid2value,n.case_filters.content,t),n}};function 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l=n(2273),c=n(4065),u=n(2974);const f=".";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 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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(f);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,u]=r,f=decodeURIComponent(u),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==f&&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 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v(e,t){try{if(!t.cohort)throw"cohort missing from ds";e.ds=t;const n=[];for(const t of[0,1,2]){const s="term"+t,r=s+"_id";"string"==typeof e[r]?(e[r]=decodeURIComponent(e[r]),e[s]=e.ds.cohort.termdb.q.termjsonByOneid(e[r])):"string"==typeof e[s]&&(e[s]=JSON.parse(decodeURIComponent(e[s])));const o=s+"_q";e[s]&&n.push({term:e[s],q:e[o]})}if(e.term2){if("survival"==e.term2.type&&"survival"==e.term1.type)throw"term and overlay are both survival terms - only one could be a survival term";if("survival"!=e.term2.type&&"survival"!=e.term1.type)throw"no survival terms, either the main term OR the overlay term must be a survival term"}else if("survival"!=e.term1.type)throw"non-survival term";if(e.term0&&"survival"==e.term0.type)throw"term0 must not be a survival term";const s=function(e){if(e.term1&&"survival"==e.term1.type)return 1;if(!e.term2)throw"term1.type is not survival and term2 is missing";if("survival"!=e.term2.type)throw"both term1 and term2 are not survival type";return 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n=e.name;if("geneVariant"==e.type){if(!t[n]||!t[n].values)return"Wildtype";const e=t[n].values.filter((e=>"Blank"!=e.class));return e.find((e=>"WT"!=e.class))?`${n} Variant`:e.find((e=>"WT"==e.class))?`${n} Wildtype`:t[n].values.length>e.length?"Not tested":"Not sure"}throw`cannot get series key for term='${n}'`}var _=n(8599),k=n(3795),q=n(1575),x=n(2188);var N=n(478),S=n(1271);async function A(e,t,n,s){!function(e,t){if(!e.chr)throw"q.chr missing";if(e.start=Number(e.start),e.stop=Number(e.stop),!Number.isInteger(e.start)||!Number.isInteger(e.stop))throw"q.start/stop is not integer";if("object"!=typeof e.details)throw"q.details{} not object";if(!Array.isArray(e.details.groups))throw"q.details.groups[] not array";if(!e.details.groups[0])throw"q.details.groups[0] missing";if(e.details.groups.length>2)throw"q.details.groups[] has more than 2";for(const n of e.details.groups)if("filter"==n.type){if("object"!=typeof n.filter)throw".filter not an object for group type=filter"}else if("population"==n.type){if(!n.key)throw".key missing from group type=population";if(!t.queries.snvindel?.populations)throw"group type=population but this ds does not have populations";if(!t.queries.snvindel.populations.find((e=>e.key==n.key)))throw"invalid key of group type=population"}else{if("info"!=n.type)throw"unknown group type from details.groups[]";if(!n.infoKey)throw".infoKey missing from group type=info"}if(e.details.groupTestMethods){if(!Array.isArray(e.details.groupTestMethods))throw"details.groupTestMethods[] not array";if(!Number.isInteger(e.details.groupTestMethodsIdx))throw"details.groupTestMethodsIdx not integer";if(!e.details.groupTestMethods[e.details.groupTestMethodsIdx])throw"invalid array index of details.groupTestMethodsIdx"}}(e,n);const r=await async function(e,t){const n={rglst:[{chr:e.chr,start:e.start,stop:e.stop}],addFormatValues:!0,variantFilter:e.variantFilter},[s,r]=e.details.groups;if("filter"==s.type&&"filter"==r?.type){n.filterObj=T(e,s.filter);const o=j(await t.queries.snvindel.byrange.get(n));n.filterObj=T(e,r.filter);const i=j(await t.queries.snvindel.byrange.get(n)),a=function(e,t,n){const[s,r]=n.details.groups,o=[];for(const n of e){n.groupData=[{refCount:n._refCount,altCount:n._altCount}];const e=t.find((e=>e.chr==n.chr&&e.pos==n.pos&&e.ref==n.ref&&e.alt==n.alt));e?n.groupData.push({refCount:e._refCount,altCount:e._altCount}):n.groupData.push({refCount:0,altCount:0}),o.push(n)}for(const n of t){e.find((e=>e.chr==n.chr&&e.pos==n.pos&&e.ref==n.ref&&e.alt==n.alt))||(n.groupData=[{refCount:0,altCount:0},{refCount:n._refCount,altCount:n._altCount}],o.push(n))}return o}(o.mlst,i.mlst,e);return{mlst:a,totalSampleCount_group1:C(o.mlst),totalSampleCount_group2:C(i.mlst)}}n.filterObj=T(e);const o=await t.queries.snvindel.byrange.get(n),i=j(o);"filter"==s.type?i.totalSampleCount_group1=C(o):"filter"==r?.type&&(i.totalSampleCount_group2=C(o));return i}(e,n);if(1==e.details.groups.length)M(n,r.mlst,e.details.groups[0]);else{if(2!=e.details.groups.length)throw"q.details.groups.length not 1 or 2";await async function(e,t,n){const[s,r]=t.groups;if("filter"==s.type&&"filter"==r.type)return void await async function(e,t,n){const s=t.groupTestMethods[t.groupTestMethodsIdx];if(!s)throw"details.groupTestMethodsIdx out of bound";switch(s.name){case"Allele frequency difference":return void I(e,t,n);case"Fisher's exact test":return void await F(n);default:throw"unknown value from groupTestMethods[]"}}(e,t,n.mlst);if("population"==s.type&&"filter"==r.type||"population"==r.type&&"filter"==s.type)return void await async function(e,t,n){const s=await async function(e,t,n){const s=t.groups.find((e=>"population"==e.type));if(!s)return;if(!s.adjust_race)return;const r=e.queries.snvindel.populations.find((e=>e.key==s.key));if(!r)throw"invalid group.key for population";const o=new Set;for(const e of n.mlst)for(const t of e.samples)o.add(t.sample_id);const i=new Map;let a=0;for(const t of r.sets){const n={infokey_AC:t.infokey_AC,infokey_AN:t.infokey_AN,average:0},s=await(0,c.J4)({ds:e,key:t.key});for(const e of s){if(!o.has(e.sample))continue;const t=Number(e.value);Number.isFinite(t)&&(n.average+=t,a+=t)}i.set(t.key,n)}for(const[e,t]of i)t.average/=a;n.pop2average={};for(const[e,t]of i)n.pop2average[e]=t.average;return i}(e,t,n);for(const r of n.mlst)r.groupData=E(e,t,r,s);const r=t.groupTestMethods[t.groupTestMethodsIdx];if(!r)throw"details.groupTestMethodsIdx out of bound";switch(r.name){case"Allele frequency difference":return void I(e,t,n.mlst);case"Fisher's exact test":return void await F(n.mlst);default:throw"unknown value from groupTestMethods[]"}}(e,t,n);I(e,t,n.mlst)}(n,e.details,r)}for(const e of r.mlst)delete e.samples,delete e._altCount,delete e._refCount;t.send(r)}function C(e){const t=new Set;for(const n of e)if(n.samples)for(const e of n.samples)t.add(e.sample_id);return t.size}function j(e){const t={mlst:[],skipMcountWithoutAlt:0};for(const n of e){const[e,s]=O(n);0!=e?(n._altCount=e,n._refCount=s-e,t.mlst.push(n)):t.skipMcountWithoutAlt++}return t}function T(e,t){const n=[e.filter];if(t)n.push(t);else for(const t of e.details.groups)"filter"==t.type&&n.push(t.filter);return(0,N.xH)(n)}function M(e,t,n){if("filter"!=n.type)if("info"!=n.type){if("population"!=n.type)throw"unknown type of single group";{const s=e.queries.snvindel.populations.find((e=>e.key==n.key));if(!s)throw"unknown population";for(const e of t){let t=0,n=0;for(const r of s.sets)t+=Number(e.info[r.infokey_AC]||0),n+=Number(e.info[r.infokey_AN]||0);e.nm_axis_value=t/n}}}else{if(!n.infoKey)throw"infoKey missing on single group.type=info";for(const e of t){const t=e.info[n.infoKey];if(null==t);else{const n=Number(t);Number.isNaN(n)||(e.nm_axis_value=n)}}}else for(const e of t)e.nm_axis_value=Number((e._altCount/(e._altCount+e._refCount)).toPrecision(2))}function O(e){let t=0,n=0;for(const s of e.samples){if(!s?.formatK2v?.GT)continue;const r=s.formatK2v.GT.split("/").map(Number);n+=r.length;for(const n of r)n==e.altAlleleIdx&&t++}return[t,n]}function 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 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s=t.query;(0,h.Y5)(s,t.cookies);try{const r=e[s.genome];if(!r)throw"invalid genome";const[o,l]=P(r,s);if(s.findterm)return await 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,e.cohortStr,e.treeFilter,e.usecase);a.push(...l.map(G));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 u.update_image(s,n):s.getgroup?await u.getgroup(s,n):await u.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,f.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 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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 a=[];if(o)try{a=r.q.getProfileFacilities(),n.send(a)}catch(e){n.send({error:e.message||e})}else n.send({error:"Requires sign in to access the sample data"})}(0,t,n,o,l);if("getAllSamples"==s.for)return async function(e,t,n,s){const r=i.i.canDisplaySampleIds(t,s);let o=[];r&&(o=Object.fromEntries(s.sampleId2Name));n.send(o)}(0,t,n,o);if("getAllSamplesByName"==s.for)return async function(e,t,n,s){if(!i.i.canDisplaySampleIds(t,s))return n.send({});if(s.queries?.singleCell?.samples?.get){const e=await s.queries.singleCell.samples.get(),t={};for(const n of e.samples)t[n.sample]=s.cohort.termdb.q.sampleName2id(n.sample);return void n.send(t)}{let t=s.sampleName2Id;if(e.filter){e.ds=s;const n=await(0,c.cf)(e.filter,e.ds,!0);t=new Map;for(const e of n)t.set(e.name,e.id)}n.send(Object.fromEntries(t))}}(s,t,n,o);if("DEanalysis"==s.for)return await async function(e,t,n){if(!n.queries?.rnaseqGeneCount)throw"not enabled by this dataset";const s=await n.queries.rnaseqGeneCount.get(e);t.send(s)}(s,n,o);throw"termdb: doesn't know what to do"}catch(e){n.send({error:e.message||e}),e.stack?console.log(e.stack):console.log(e)}}}function P(e,t){{const n=e.datasets[t.dslabel];if(n){if(n?.cohort?.termdb)return[n,n.cohort.termdb];throw".cohort.termdb not found on this dataset"}}if(!e.termdbs)throw"invalid dslabel";const n=e.termdbs[t.dslabel];if(!n)throw"invalid dslabel";if(!n.cohort)throw"ds.cohort missing for genome-level termdb";if(!n.cohort.termdb)throw"ds.cohort.termdb{} missing for a genome-level termdb";return[n,n.cohort.termdb]}function G(e){return JSON.parse(JSON.stringify(e))}},2974:(e,t,n)=>{"use strict";n.d(t,{Yu:()=>f,fZ:()=>d,gh:()=>p,te:()=>m});var s=n(1017),r=n.n(s),o=n(8907),i=n(5257),a=(n(9157),n(7147),n(7219),n(334)),l=n.n(a),c=n(3345),u=n(8599);async function f(e,t,n){try{return function(e,t,n){if(!t.cohort)throw"cohort missing from ds";if(!e.terms)throw"missing 'terms' parameter";e.ds=t,e.genome=n;for(const t of e.terms)t.term.name||(t.term=e.ds.cohort.termdb.q.termjsonByOneid(t.term.id)),t.q||console.log("do something??");if(e.currentGeneNames&&!Array.isArray(e.currentGeneNames))throw"currentGeneNames[] is not array";e.filter0&&"string"==typeof e.filter0&&(e.filter0=JSON.parse(e.filter0))}(e,t,n),await async function(e){const[t,n]=function(e){const t=[],n=[];for(const s of e){const e=s.term.type;"snplst"==e||"snplocus"==e||"geneVariant"==e?n.push(s):t.push(s)}return[t,n]}(e.terms),[s,r]=await async function(e,t){if(!t.length)return[{},{}];if(e.ds?.cohort?.db)return await p(e,t);if(e.ds?.variant2samples?.get)return await async function(e,t){const n={filter0:e.filter0,filterObj:e.filter,genome:e.genome,get:"samples",twLst:t,gdcUseCaseuuid:!0,isHierCluster:e.isHierCluster};e.rglst&&(n.rglst=e.rglst);if(e.currentGeneNames){n.geneTwLst=[];for(const t of e.currentGeneNames)n.geneTwLst.push({term:{name:t,type:"geneVariant"}})}const s=await e.ds.variant2samples.get(n),r={};for(const e of s.samples){const n={sample:e.sample_id};for(const s of t){const t=e[s.term.id];Array.isArray(t)&&null!=t[0]&&null!=t[0]?n[s.term.id]={key:t[0],value:t[0]}:null!=t&&null!=t&&(n[s.term.id]={key:t,value:t})}r[e.sample_id]=n}return[r,s.byTermId||{}]}(e,t);throw"unknown method for dictionary terms"}(e,t);if(t.length&&!Object.keys(s).length)return{samples:s,refs:{byTermId:r,bySampleId:{}}};const i=await async function(e,t){if(!t.find((e=>"snplst"==e.term.type||"snplocus"==e.term.type)))return;if(!e.filter)return;return new Set((await(0,o.cf)(e.filter,e.ds)).map((e=>e.id)))}(e,n);for(const o of n)if("geneVariant"==o.term.type){e.ds.cohort?.termdb?.getGeneAlias&&(r[o.term.name]=e.ds.cohort?.termdb?.getGeneAlias(e,o));const n=await e.ds.mayGetGeneVariantData(o,e);for(const[e,r]of n.entries())o.term.name in r&&(t.length||e in s||(s[e]={sample:e}),s[e]&&(s[e][o.term.name]=r[o.term.name]))}else{if("snplst"!=o.term.type&&"snplocus"!=o.term.type)throw"unknown type of non-dictionary 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c={};if("linear"==e.regressionType&&(c[n.id]=a.value),"logistic"==e.regressionType&&(c[n.id]=a.key===e.outcome.refGrp?0:1),"cox"==e.regressionType){c[n.timeToEvent.eventId]=a.key;const{age_start:t,age_end:s}=a.value;c[n.timeToEvent.timeId]=s-t,"age"==e.outcome.q.timeScale&&(c[n.timeToEvent.agestartId]=t,c[n.timeToEvent.ageendId]=s)}for(const e of s){const t=i.get(e.id);c[e.id]=t?"numeric"===e.rtype?t.value:t.key:null}r.push(c)}const o={regressionType:e.regressionType,binpath:p().binpath,data:r,outcome:n,independent:s};return o}(e,n);w=(new Date).getTime(),_.NodeJS.makeRinput=(w-v)/1e3+" sec",function(e){const t=e.regressionType,n=e.outcome;if(e.data.length<b)throw"too few samples to fit model";let s=e.independent.length;if("cox"==t)if("time"==n.timeToEvent.timeScale)s+=2;else{if("age"!=n.timeToEvent.timeScale)throw"unknown cox regression time scale";s+=4}else s+=1;if(e.data.find((e=>Object.keys(e).length!=s)))throw"unequal number of variables in data 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s=e.outcome.timeToEvent;t.outcome_time=s.timeId,n[s.timeId]="outcome_time",t.outcome_event=s.eventId,n[s.eventId]="outcome_event","age"==s.timeScale&&(t.outcome_agestart=s.agestartId,t.outcome_ageend=s.ageendId,n[s.agestartId]="outcome_agestart",n[s.ageendId]="outcome_ageend")}for(const[s,r]of e.independent.entries())t["id"+s+"_"]=r.id,n[r.id]="id"+s+"_";if(e.outcome.id=n[e.outcome.id],e.outcome.timeToEvent){const t=e.outcome.timeToEvent;t.timeId=n[t.timeId],t.eventId=n[t.eventId],"age"==t.timeScale&&(t.agestartId=n[t.agestartId],t.ageendId=n[t.ageendId])}for(const t of e.independent)if(t.id=n[t.id],t.interactions&&t.interactions.length>0)for(const[e,s]of t.interactions.entries())t.interactions[e]=n[s];for(const t of e.data)for(const e in t)t[n[e]]=t[e],delete t[e];return[t,n]}(s),l={resultLst:[]};return await Promise.all([A(s,r,e,l),C(e,n,s,l)]),console.log("benchmark:",_),l}catch(e){return e.stack&&console.log(e.stack),{error:e.message||e}}}function 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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n.independent)t.interactions.includes(e.id)&&(r.interactions||(r.interactions=[]),r.interactions.push(t.id));t.push(r)}if(e.q.restrictAncestry)for(const n of e.q.restrictAncestry.pcs.keys())t.push({id:n,name:n,type:"float",rtype:"numeric"})}function S(e){if("condition"==e.term.type){for(const t of e.q.groups)if(t.name!=e.refGrp)return t;throw"nonref group not found for logistic outcome"}if("predefined-groupset"==e.q.type){if(!e.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!Number.isInteger(e.q.groupsetting.predefined_groupset_idx))throw'outcome.q.predefined_groupset_idx not integer when q.type is "predefined-groupset"';if(!e.term.groupsetting)throw"outcome.term.groupsetting missing";const t=e.term.groupsetting.lst[e.q.groupsetting.predefined_groupset_idx];if(!t)throw"groupset not found by outcome.q.predefined_groupset_idx";const n=t.groups.find((t=>t.name!=e.refGrp));if(!n)throw"non-ref group not found for predefined-groupset";return 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if(n?.byTermId[t.term.id]?.bins){const r=n.byTermId[t.term.id].bins;for(const t of r)e[t.name]&&s.push([t.name,e[t.name]]);for(const[t,n]of Object.entries(e))s.some((e=>e[0]===t))||s.push([t,n])}else s=Object.entries(e),s.sort(((e,n)=>{let s,r;for(const o in t.term.values){const i=t.term.values[o];(i.label&&e[0]==i.label||o==e[0])&&(s=i),(i.label&&n[0]==i.label||o==n[0])&&(r=i)}return s&&"order"in s?s?.order<r?.order?-1:1:e[1].sampleCount>n[1].sampleCount?-1:1}));return s}function k(e,t){if(!e)return!0;return!e.values?.[t]?.uncomputable}async function q(e,t,n){const s=t.coords,r=o().join(l().cachedir,Math.random().toString()+".json");await(0,i.Sf)(r,JSON.stringify(s));let a=await(0,p.default)(o().join(l().binpath,"utils/lowess.R"),[],[r]);a=JSON.parse(a);const c=[];for(const[e,t]of Object.entries(a.x))c.push([t,a.y[e]]);return n.send(c)}},394:(e,t,n)=>{"use strict";n.d(t,{JV:()=>l,jj:()=>c,qN:()=>u});var s=n(334),r=n.n(s),o=n(3345),i=n(1575),a=n(6191);function 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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Map;f.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;f.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=?")};f.getSample2value=(n,r=null)=>{const o=f.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;f.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}}}f.getSupportedChartTypes=t=>{u(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");if(e.queries.singleCell)for(const e in n)n[e].push("singleCellPlot")}return n},f.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])},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(e){const t=e.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(t.map((e=>e.name)))}function u(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)),u=n.n(c),f=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 function(e,t,n,s){if(!e.cacheid)throw"cacheid missing";if(u().cache_snpgt.fileNameRegexp.test(e.cacheid))throw"invalid cacheid";let r,o;if(n.track){if(r=n.track.vcf,!r)throw"ds.track.vcf missing"}else r=n.queries.snvindel.byrange._tk;if(e.filter){const t=new Set((await l.cf(e.filter,n)).map((e=>e.id)));if(0==t.size)throw"no samples from filter";o=r.samples.map((e=>t.has(e.name)))}else o=r.samples.map((e=>!0));const c=(await a.b5(i().join(u().cache_snpgt.dir,e.cacheid))).split("\n"),f=new Set,d=[];for(let e=1;e<c.length;e++){const t=c[e].split("\t"),n=t[0],s=t[3],i={},a={};for(let e=u().cache_snpgt.sampleColumn;e<t.length;e++){const n=t[e];if(!n)continue;if(!o[e-u().cache_snpgt.sampleColumn])continue;f.add(r.samples[e-u().cache_snpgt.sampleColumn].name),a[n]=1+(a[n]||0);const s=n.split("/");for(const e of s)i[e]=1+(i[e]||0)}const l=[];for(const e in i)l.push({allele:e,count:i[e],isRef:e==s});d.push({snpid:n,alleles:l,gt2count:a})}return{numOfSampleWithAnyValidGT:f.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(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: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(f,(()=>{}));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(u().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(","),u={snpid:c,chr:e.chr,pos:r};(0,f.H)(o,a,l,u,s[4],s[1]);for(const e of u.mlst)e.vcf_id&&(e.mname=e.vcf_id);g.snps.push(u);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(u().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?"<=":"<"} ${e.stop}`)}0!=n.length&&t.push("-i",n.join(" && "))}},8907:(e,t,n)=>{"use strict";n.d(t,{yT:()=>C,YG:()=>T,g5:()=>S,J4:()=>N,B9:()=>q,cf:()=>k,tt:()=>x,Bi:()=>A,ig:()=>M});var s={};n.r(s),n.d(s,{binary:()=>f,continuous:()=>l,cubicSpline:()=>c,discrete:()=>u});var r={};n.r(r),n.d(r,{groupset:()=>m,values:()=>d});var o={};n.r(o),n.d(o,{binary:()=>g,cox:()=>b,cuminc:()=>y,discrete:()=>h});var i=n(4048),a=n(5257);const l={getCTE(e,t,n,s,r,o,i){r.push(t.id);const a=C(t,s);return r.push(...a.values),{sql:`${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=? ${a.clause}\n\t\t\t)`,tablename:e}}},c=l,u={getCTE(e,t,n,s,r,o,i){r.push(t.id);const a=T(s,t,n,o,i),l=[],c=new Map;s.bin_size;for(const e of a)!("name"in e)&&e.label&&(e.name=e.label),c.set(e.name,e),l.push(`SELECT '${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${e.startinclusive?1:0} AS startinclusive,\n\t\t\t\t${e.stopinclusive?1:0} AS stopinclusive`);const u=[];if(t.values)for(const e in t.values){const n=t.values[e].uncomputable;if(s.computableValuesOnly&&n)continue;if(!s.computableValuesOnly&&!n)continue;u.push(e);const r=t.values[e];l.push(`SELECT '${r.label}' AS name,\n\t ${e} AS start,\n\t 0 AS stop,\n\t 1 AS unannotated,\n\t 0 AS startunbounded,\n\t 0 AS stopunbounded,\n\t 0 AS startinclusive,\n\t 0 AS stopinclusive`),c.set(r.label,{is_unannotated:!0,value:e,label:r.label})}const f="bin_defs_"+o,d=C(t,s,"a");r.push(...d.values);return{sql:`${f} AS (\n\t\t\t\t${l.join("\nUNION ALL\n")}\n\t\t\t),\n\t\t\t${e} AS (\n\t\t\t\tSELECT\n\t\t\t\t\tsample,\n\t\t\t\t\tb.name AS key,\n\t\t\t\t\tvalue\n\t\t\t\tFROM\n\t\t\t\t\tanno_${t.type} a\n\t\t\t\tJOIN ${f} b ON\n\t\t\t\t\t( b.unannotated=1 AND value=b.start )\n\t\t\t\t\tOR\n\t\t\t\t\t(\n\t\t\t\t\t\tb.unannotated=0 AND\n\t\t\t\t\t\t${u.length?"value NOT IN ("+u.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=? ${d.clause}\n\t\t\t)`,tablename:e,name2bin:c,bins:a}}},f=u,d={getCTE(e,t,n,s,r){r.push(t.id);const o=C(t,s);return r.push(...o.values),{sql:`${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?" AND sample IN "+t.CTEname:""}`;return e.ds.cohort.db.connection.prepare(r).all(n)}async function S(e,t={}){"string"==typeof e.filter&&(e.filter=JSON.parse(decodeURIComponent(e.filter)));const n=Object.assign({withCTEs:!0,columnas:"t1.sample AS sample",groupby:""},t),s=await(0,a.w)(e.filter,e.ds),r=s?s.values.slice():[],o=await A(e,r,0,s),i=await A(e,r,1,s),l=await A(e,r,2,s),c=[o,i,l].map(((e,t)=>`\n\t\tSELECT sample, key, value, ${t} as termNum\n\t\tFROM ${e.tablename}\n\t\t${s?"WHERE sample IN "+s.CTEname:""}\n\t`)).join("\nUNION ALL\n"),u=`WITH\n\t\t${s?s.filters+",":""}\n\t\t${o.sql},\n\t\t${i.sql},\n\t\t${l.sql}\n\t\t${c}`;try{const t=e.ds.cohort.db.connection.prepare(u).all(r),a=new Map;for(const e of t){a.has(e.sample)||a.set(e.sample,{sample:e.sample});const t=a.get(e.sample),n=`key${e.termNum}`;n in t||(t[n]=[]),t[n].push(e)}const c=[],f=new Map;for(const t of a.values())if("key1"in t){if(e.term0_q&&e.term0_id){if(!("key0"in t))continue}else t.key0=[{key:"",value:""}];if(e.term2_q&&(e.term2_id||"samplelst"===e.term2.type)){if(!("key2"in t))continue}else t.key2=[{key:"",value:""}];t.rows=[];for(const e of t.key0)for(const n of t.key1)for(const s of t.key2)t.rows.push({sample:t.sample,key0:e.key,val0:e.value,key1:n.key,val1:n.value,key2:s.key,val2:s.value});for(const e of t.rows)if(n.groupby){if(!f.has(e[n.groupby])){const t=Object.assign({samplecount:0},e);c.push(t),f.set(e[n.groupby],t)}f.get(e[n.groupby]).samplecount++}else c.push(e)}return n.withCTEs?{lst:c,CTE0:o,CTE1:i,CTE2:l,filter:s}:c}catch(e){throw console.log("error in sql:\n",M(u,r)),e}}async function A(e,t,n,i,a=null){const l=a&&a.term||e[`term${n}`],c=l?l.id:e["term"+n+"_id"];if("samplelst"!=l?.type)if(a||1!=n){if(!c){const e="samplekey_"+n;return{tablename:e,sql:`${e} AS (\nSELECT null AS sample, '' as key, '' as value\n)`}}}else if(!c)throw"missing term1 id";const u=l&&l.type?l:e.ds.cohort.termdb.q.termjsonByOneid(c);if(!u)throw`no term found by id='${c}'`;let f=a&&a.q||e["term"+n+"_q"]||{};"string"==typeof f&&(f=JSON.parse(decodeURIComponent(f)));const d="samplekey_"+n;let p;if("categorical"==u.type){const n=j(u,f);p=await r[n?"groupset":"values"].getCTE(d,u,e.ds,f,t,n)}else if("integer"==u.type||"float"==u.type){const r="spline"==f.mode?"cubicSpline":f.mode||"discrete";p=await s[r].getCTE(d,u,e.ds,f,t,n,i)}else if("condition"==u.type){const n=f.mode||"discrete";p=await o[n].getCTE(d,u,e.ds,f,t)}else if("survival"==u.type)p=function(e,t,n,s,r){return s.push(t.id),{sql:`${e} AS (\n\t\t\tSELECT sample, exit_code as key, tte AS value\n\t\t\tFROM survival s\n\t\t\tWHERE s.term_id=?\n\t\t\t${r?"AND s.sample IN "+r.CTEname:""}\n\t\t)`,tablename:e}}(d,u,0,t,i);else{if("samplelst"!=u.type)throw"unknown term type";p=await _.getCTE(d,a||{term:u,q:f},t)}return p}function C(e,t,n=""){if(!e.values||!t.computableValuesOnly)return{values:[],clause:""};const 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