npm - @sjcrh/proteinpaint-server - Versions diffs - 2.25.0 → 2.26.0 - Mend

@sjcrh/proteinpaint-server 2.25.0 → 2.26.0

This diff represents the content of publicly available package versions that have been released to one of the supported registries. The information contained in this diff is provided for informational purposes only and reflects changes between package versions as they appear in their respective public registries.

Files changed (11) hide show

package/dataset/clinvar.hg19.js +3 -3
package/dataset/clinvar.hg38.js +20 -3
package/genome/cgc.js +7 -0
package/genome/hg19.js +2 -0
package/genome/hg38.js +9 -2
package/package.json +8 -8
package/routes/genelookup.ts +58 -0
package/routes/healthcheck.ts +72 -0
package/server.js +1 -1
package/utils/fastclust.R +8 -6
package/src/routes/healthcheck.ts +0 -92

package/server.js CHANGED Viewed

	@@ -1 +1 @@
1	- (()=>{var t={4052:(t,e,n)=>{"use strict";n.r(e),n.d(e,{schemeCategory20:()=>r});const r=["#1f77b4","#aec7e8","#ff7f0e","#ffbb78","#2ca02c","#98df8a","#d62728","#ff9896","#9467bd","#c5b0d5","#8c564b","#c49c94","#e377c2","#f7b6d2","#7f7f7f","#c7c7c7","#bcbd22","#dbdb8d","#17becf","#9edae5"]},6733:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>i,parseline:()=>s});var r=n(2273),o=n(8064);function i(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid file header for CNV";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("gene");return-1==o?"gene missing from header":(n[o]="gene",o=r("cnv"),-1==o?"CNV missing from header":(n[o]="cnv",o=r("sample","sample_name","tumor_sample_barcode"),-1!=o&&(n[o]="sample"),o=r("patient","donor","target_case_id"),-1!=o&&(n[o]="patient"),o=r("disease"),-1!=o&&(n[o]="disease"),o=r("origin"),-1!=o&&(n[o]="origin"),o=r("sampletype","sample type","sample_type"),-1!=o&&(n[o]="sampletype"),e.cnv.header=n,e.cnv.loaded=!0,!1))}function s(t,e,n){if(""==e\|\|"#"==e[0])return;const i=e.split("\t"),s={};for(let t=0;t<n.cnv.header.length;t++)s[n.cnv.header[t]]=i[t];if(!s.gene)return void n.cnv.badlines.push([t,"missing gene",i]);if(!s.cnv)return void n.cnv.badlines.push([t,"missing cnv value",i]);switch(s.cnv.toLowerCase()){case"amplification":case"gain":s.class=r.mclasscnvgain;break;case"deletion":case"loss":s.class=r.mclasscnvloss;break;case"loh":s.class=r.mclasscnvloh;break;default:n.cnv.badlines.push([t,"invalid cnv value: "+s.cnv,i]),s.class=null}if(!s.class)return;if(o.parsesample(s,n,t,i,n.cnv.badlines))return;s.dt=r.dtcnv,n.good++;const a=n.geneToUpper?s.gene.toUpperCase():s.gene;a in n.data\|\|(n.data[a]=[]),n.data[a].push(s)}},5558:(t,e,n)=>{"use strict";n.r(e),n.d(e,{parseheader:()=>i,parseline:()=>s});var r=n(2273),o=n(8064);function i(t,e){const n=t.toLowerCase().split("\t");if(n.length<=1)return"invalid header line 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t.patient?t.sample?t.sampletype=t.sample:t.sample=t.sampletype=t.patient:t.sample&&(t.sampletype=t.sample);if(t.origin){switch(t.origin.toLowerCase()){case"r":case"relapse":s=r.moriginrelapse,t.isrim2=!0;break;case"g":case"germline":s=r.morigingermline,t.isrim1=!0;break;case"gp":case"germline pathogenic":s=r.morigingermlinepathogenic,t.isrim1=!0;break;case"gnp":case"germline nonpathogenic":case"germline non-pathogenic":s=r.morigingermlinenonpathogenic,t.isrim1=!0;break;case"s":case"somatic":case"diagnosis":s=r.moriginsomatic}}if(t.origin=s,!t.sample&&!t.patient)return;const a="no patient/individual name";if(t.patient?(e.patient2st[t.patient]\|\|(e.patient2st[t.patient]={}),e.patient2st[t.patient][t.sampletype]=t.sample):(e.patient2st[a]\|\|(e.patient2st[a]={}),e.patient2st[a][t.sampletype]=t.sample),t.sample&&t.disease)if(t.sample in e.sample2disease){if(t.disease!=e.sample2disease[t.sample])return e.snv.badlines.push([n,'conflict of disease types for sample "'+t.sample+'": 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"+s.class,i]);s.class=a}if(o.parsesample(s,n,t,i,n.snv.badlines))return;if(!s.chr)return void n.snv.badlines.push([t,"missing chromosome",i]);if(0!=s.chr.toLowerCase().indexOf("chr")&&(s.chr="chr"+s.chr),!s.pos)return void n.snv.badlines.push([t,"missing chromosome position",i]);const l=Number.parseInt(s.pos);if(Number.isNaN(l))return void n.snv.badlines.push([t,"invalid chromosome position",i]);if(s.pos=l-1,null!=s.maf_tumor_v2&&null!=s.maf_tumor_v1){if(""==s.maf_tumor_v2);else{let e=Number.parseInt(s.maf_tumor_v1),r=Number.parseInt(s.maf_tumor_v2);if(Number.isNaN(e)\|\|Number.isNaN(r))return void n.snv.badlines.push([t,"invalid maf_tumor mutant and/or total read count",i]);s.maf_tumor={f:e/r,v1:e,v2:r}}delete s.maf_tumor_v1,delete s.maf_tumor_v2}if(null!=s.maf_normal_v1&&null!=s.maf_normal_v2){if(""==s.maf_normal_v2);else{let e=Number.parseInt(s.maf_normal_v1),r=Number.parseInt(s.maf_normal_v2);if(Number.isNaN(e)\|\|Number.isNaN(r))return void n.snv.badlines.push([t,"invalid 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from header":(r[i]="position1",i=o("pos_b","position_b","position2","posb"),-1==i?"pos_b missing from header":(r[i]="position2",i=o("isoform_a","refseq_a","refseq1","isoform1","sv_refseqa"),-1==i?"isoform_a missing from header":(r[i]="isoform1",i=o("isoform_b","refseq_b","refseq2","isoform2","sv_refseqb"),-1==i?"isoform_b missing from header":(r[i]="isoform2",i=o("strand_a","orta"),-1==i?"strand_a missing from header":(r[i]="strand1",i=o("strand_b","ortb"),-1==i?"strand_b missing from header":(r[i]="strand2",i=o("sample","sample_name","tumor_sample_barcode"),-1!=i&&(r[i]="sample"),i=o("patient","donor","target_case_id"),-1!=i&&(r[i]="patient"),i=o("sampletype","sample type","sample_type"),-1!=i&&(r[i]="sampletype"),i=o("disease"),-1!=i&&(r[i]="disease"),i=o("origin"),-1!=i&&(r[i]="origin"),n?(e.sv.loaded=!0,e.sv.header=r):(e.fusion.loaded=!0,e.fusion.header=r),!1))))))))))}function s(t,e,n,i){if(""==e\|\|"#"==e[0])return;const s=e.split("\t"),a={},l=i?n.sv.header:n.fusion.header,c=i?n.sv.badlines:n.fusion.badlines;for(let t=0;t<l.length;t++)a[l[t]]=s[t];if(!a.chr1)return void c.push([t,"missing chr1",s]);if(0!=a.chr1.toLowerCase().indexOf("chr")&&(a.chr1="chr"+a.chr1),!a.chr2)return void c.push([t,"missing chr2",s]);0!=a.chr2.toLowerCase().indexOf("chr")&&(a.chr2="chr"+a.chr2);let u=a.position1;if(!u)return void c.push([t,"missing position1",s]);let f=Number.parseInt(u);if(Number.isNaN(f)\|\|f<=0)c.push([t,"invalid value for position1",s]);else if(a.position1=f,u=a.position2,u){if(f=Number.parseInt(u),Number.isNaN(f)\|\|f<=0)c.push([t,"invalid value for position2",s]);else if(a.position2=f,!r.parsesample(a,n,t,s,c)){if(a.isoform1&&-1!=a.isoform1.indexOf(",")){const t=a.isoform1.split(",");a.isoform1=void 0;for(const e of t)""!=e&&(a.isoform1=e)}if(a.isoform2&&-1!=a.isoform2.indexOf(",")){const t=a.isoform2.split(",");a.isoform2=void 0;for(const e of t)""!=e&&(a.isoform2=e)}if(a.gene1\|\|(a.isoform1=void 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t={dt:i?o.dtsv:o.dtfusionrna,class:i?o.mclasssv:o.mclassfusionrna,isoform:a.isoform2,mname:a.gene1\|\|a.chr1,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene2.toUpperCase():a.gene2;n.data[e]\|\|(n.data[e]=[]),n.data[e].push(t)}}}else c.push([t,"missing position2",s])}function a(t){const e={};for(const n in t){if("pairlst"==n)continue;const r=t[n];"object"!=typeof r&&(e[n]=r)}if(t.pairlst){e.pairlst=[];for(const n of t.pairlst){const t={};for(const e in n)"a"!=e&&"b"!=e&&"interstitial"!=e&&(t[e]=n[e]);if(n.a){t.a={};for(const e in n.a){const r=n.a[e];"object"!=typeof r&&(t.a[e]=r)}}if(n.b){t.b={};for(const e in n.b){const r=n.b[e];"object"!=typeof r&&(t.b[e]=r)}}if(n.interstitial){t.interstitial={};for(const e in n.interstitial){const 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e=yt[t],n={species:e.species,name:t,hasSNP:!!e.snp,hasIdeogram:e.genedb.hasIdeogram,hasClinvarVCF:!!e.clinvarVCF,fimo_motif:!!e.fimo_motif,blat:!!e.blat,geneset:e.geneset,defaultcoord:e.defaultcoord,isdefault:e.isdefault,majorchr:e.majorchr,majorchrorder:e.majorchrorder,minorchr:e.minorchr,tracks:e.tracks,hicenzymefragment:e.hicenzymefragment,datasets:{}};if(e.termdbs){n.termdbs={};for(const t in e.termdbs)n.termdbs[t]={label:e.termdbs[t].label}}for(const t in e.datasets){const r=e.datasets[t];r.isMds3?n.datasets[r.label]={isMds3:!0,noHandleOnClient:r.noHandleOnClient,label:r.label}:r.isMds?n.datasets[r.label]={isMds:!0,mdsIsUninitiated:!0,noHandleOnClient:r.noHandleOnClient,label:r.label}:n.datasets[r.label]={isofficial:!0,legacyDsIsUninitiated:!0,noHandleOnClient:r.noHandleOnClient,label:r.label}}if(e.hicdomain){n.hicdomain={groups:{}};for(const t in e.hicdomain.groups){const r=e.hicdomain.groups[t];n.hicdomain.groups[t]={name:r.name,reference:r.reference,sets:{}};for(const e in r.sets)n.hicdomain.groups[t].sets[e]={name:r.sets[e].name,longname:r.sets[e].longname}}}return n}function Mt(t){const e={noHandleOnClient:t.noHandleOnClient,sampleselectable:t.sampleselectable,label:t.label,dsinfo:t.dsinfo,stratify:t.stratify,cohort:t.cohort,vcfinfofilter:t.vcfinfofilter,info2table:t.info2table,info2singletable:t.info2singletable,url4variant:t.url4variant,itemlabelname:t.itemlabelname};if(t.snvindel_attributes){e.snvindel_attributes=[];for(const n of t.snvindel_attributes){const t={};for(const e in n)if("lst"==e){t.lst=[];for(const e of n.lst){const n={};for(const t in e)n[t]=e[t];t.lst.push(n)}}else t[e]=n[e];e.snvindel_attributes.push(t)}}t.snvindel_legend&&(e.snvindel_legend=t.snvindel_legend);const n={};let r=!1;for(const e of t.queries)e.vcf&&(r=!0,n[e.vcf.vcfid]=e.vcf);return r&&(e.id2vcf=n),e}function Tt(t){const e={isMds:!0,noHandleOnClient:t.noHandleOnClient,label:t.label,version:t.version,annotationsampleset2matrix:t.annotationsampleset2matrix,mutationAttribute:t.mutationAttribute,locusAttribute:t.locusAttribute,alleleAttribute:t.alleleAttribute,hide_genotypedownload:t.hide_genotypedownload,hide_phewas:t.hide_phewas,sample2bam:t.sample2bam};if(t.queries&&(e.queries={}),t.track&&(e.track=K.client_copy(t)),t.singlesamplemutationjson&&(e.singlesamplemutationjson=1),t.gene2mutcount&&(e.gene2mutcount=!0,e.mutCountType=t.gene2mutcount.mutationTypes),t.assayAvailability&&(e.assayAvailability=1),t.cohort&&t.cohort.sampleAttribute){const n={};for(const e in t.cohort.sampleAttribute.attributes){const r=t.cohort.sampleAttribute.attributes[e];r.clientnoshow\|\|(n[e]=r)}e.sampleAttribute={attributes:n}}if(t.cohort){if(t.cohort.termdb&&(e.termdb={selectCohort:t.cohort.termdb.selectCohort}),t.cohort.attributes&&t.cohort.attributes.defaulthidden&&(e.cohortHiddenAttr=t.cohort.attributes.defaulthidden),t.cohort.survivalplot){e.survivalplot={samplegroupattrlst:t.cohort.survivalplot.samplegroupattrlst,plots:[]};for(const n in t.cohort.survivalplot.plots){const r=t.cohort.survivalplot.plots[n];e.survivalplot.plots.push({key:n,name:r.name,timelabel:r.timelabel})}}if(t.cohort.mutation_signature){const n={};for(const e in t.cohort.mutation_signature.sets){const r=t.cohort.mutation_signature.sets[e];n[e]={name:r.name,signatures:r.signatures}}e.mutation_signature={sets:n}}}for(const n in t.queries){const r=t.queries[n],o={name:r.name,hideforthemoment:r.hideforthemoment};if(r.istrack){if(o.istrack=!0,o.type=r.type,o.isfull=r.isfull,null!=r.nochr&&(o.nochr=r.nochr),r.infoFilter&&(o.infoFilter=r.infoFilter),r.readcountCutoff&&(o.readcountCutoff=r.readcountCutoff),r.valueLabel&&(o.valueLabel=r.valueLabel),r.valueCutoff&&(o.valueCutoff=r.valueCutoff),r.bplengthUpperLimit&&(o.bplengthUpperLimit=r.bplengthUpperLimit),r.segmeanValueCutoff&&(o.segmeanValueCutoff=r.segmeanValueCutoff),r.lohLengthUpperLimit&&(o.lohLengthUpperLimit=r.lohLengthUpperLimit),r.type==k.tkt.mdssvcnv){if(r.groupsamplebyattr&&(o.groupsamplebyattr=r.groupsamplebyattr),o.multihidelabel_fusion=r.multihidelabel_fusion,o.multihidelabel_sv=r.multihidelabel_sv,o.multihidelabel_vcf=r.multihidelabel_vcf,o.showfullmode=r.showfullmode,o.legend_vorigin=r.legend_vorigin,o.no_loh=r.no_loh,r.expressionrank_querykey){const e=t.queries[r.expressionrank_querykey];if(o.checkexpressionrank={querykey:r.expressionrank_querykey,datatype:e.datatype},e.boxplotbysamplegroup&&e.boxplotbysamplegroup.additionals){const t=[];e.boxplotbysamplegroup.attributes&&t.push(e.boxplotbysamplegroup.attributes.map((t=>t.label)).join(", "));for(const n of e.boxplotbysamplegroup.additionals)t.push(n.label);o.checkexpressionrank.boxplotgroupers=t}}if(r.vcf_querykey){o.checkvcf={querykey:r.vcf_querykey,info:t.queries[r.vcf_querykey].info,format:{}};for(const e of t.queries[r.vcf_querykey].tracks)if(e.format)for(const t in e.format)o.checkvcf.format[t]=e.format[t]}}}else{if(!r.isgenenumeric)continue;o.isgenenumeric=!0,o.datatype=r.datatype,o.no_ase=r.no_ase}e.queries[n]=o}return e}function Ct(t){const e=t.split("\t"),n=e[4],r=e[6].split(",").filter(Boolean),o=n+"/"+r.join("/");return{chrom:e[0],chromStart:Number(e[1]),chromEnd:Number(e[2]),name:e[3],observed:o,alleles:[n,...r]}}function 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e)r.rnacount={nocoverage:1},o.push((t.nochr?n.replace("chr",""):n)+":"+(r.pos+1)+"-"+(r.pos+1));return new Promise(((n,i)=>{const s=m(_t,["mpileup","--no-reference","-a","INFO/AD","-d",999999,"-r",o.join(","),"-q",r.rnapileup_q,"-Q",r.rnapileup_Q,t.url\|\|t.file],{cwd:t.dir});_.createInterface({input:s.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Zt(t);if(!n)return;const r=e.find((t=>t.pos==n.pos));if(r){const t=n.allele2count[r.ref]\|\|0,e=n.allele2count[r.alt]\|\|0;t+e>0&&(r.rnacount={ref:t,alt:e,f:e/(t+e)})}})),s.on("close",(()=>{n()}))}))}function Lt(t,e,n,r,o,i){e.hideLOHwithCNVoverlap&&Dt(o);const s=[];if(i){const t=new Map;for(const[e,n]of o){const r=i.sample2group.get(e);t.has(r)\|\|t.set(r,[]),t.get(r).push({samplename:e,items:n})}if(r)for(const e of r)if(e.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){const e=i.sample2group.get(n.sampleobj.name);t.has(e)\|\|t.set(e,[]),t.get(e).find((t=>t.samplename==n.sampleobj.name))\|\|t.get(e).push({samplename:n.sampleobj.name,items:[]})}for(const[e,n]of t)s.push({name:e,samples:n})}else if(t.cohort&&t.cohort.annotation&&e.groupsamplebyattr){const n=new Map,i=[];for(const[r,s]of o)zt(r,s,n,i,t,e);if(r)for(const o of r)if(o.dt!=k.dtsnvindel)console.log("unknown dt when grouping samples from vcf data: "+o.dt);else for(const r of o.sampledata)zt(r.sampleobj.name,[],n,i,t,e);for(const t of n.values())if(s.push(t),e.groupsamplebyattr.key2group){const n=e.groupsamplebyattr.key2group.get(t.name);n&&(t.sampletotalnum=n.samples.length)}i.length&&s.push({name:"Unannotated",samples:i});for(const e of s)for(const n of e.samples)t.cohort.annotation[n.samplename]&&(n.sampletype=t.cohort.annotation[n.samplename].sample_type)}else{const t=[];for(const[e,n]of o)t.push({samplename:e,items:n});if(r)for(const e of r)if(e.dt!=k.dtsnvindel)console.log("unknown dt when 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e=s[i.groupsamplebyattr.attrlst[t].k];if(null==e)break;l.push(e)}l.unshift(a);const c=l.join(i.groupsamplebyattr.attrnamespacer);if(!n.has(c)){const t=[];for(const e of i.groupsamplebyattr.attrlst){const n=s[e.k];if(null==n)break;const r={k:e.k,kvalue:n};e.full&&(r.full=e.full,r.fullvalue=s[e.full]),t.push(r)}const e=[];for(const t of i.groupsamplebyattr.attrlst){const n=s[t.k];if(null==n)break;const r=(t.full?s[t.full]:null)\|\|n;e.push(r)}n.set(c,{name:c,samples:[],attributes:t})}let u=!0;for(const r of n.get(c).samples)if(r.samplename==t){for(const t of e)r.items.push(t);u=!1;break}u&&n.get(c).samples.push({samplename:t,items:e})}function Bt(t){return Number.isFinite(t.dna_mintotalreads)?Number.isFinite(t.rna_mintotalreads)?Number.isFinite(t.hetsnp_minbaf)?Number.isFinite(t.hetsnp_maxbaf)?Number.isFinite(t.rnapileup_q)?Number.isFinite(t.rnapileup_Q)?void 0:"invalid value for rnapileup_Q":"invalid value for rnapileup_q":"invalid value for hetsnp_maxbaf":"invalid value for hetsnp_minbaf":"invalid value for rna_mintotalreads":"invalid value for dna_mintotalreads"}function $t(t){const e=t+".pvalue";return new Promise(((n,r)=>{const i=m("Rscript",[u.join(o.binpath,"utils/binom.R"),t,e]);i.on("close",(()=>{n(e)})),i.on("error",(t=>{r(`cannot do binom test: ${t}`)})),i.stderr.on("data",(t=>{r(`cannot do binom test: ${t}`)}))}))}function Zt(t){const e=t.split("\t");if(e.length<8)return;const n={pos:Number.parseInt(e[1])-1},r=[e[3],...e[4].split(",")],o={};for(const t of e[7].split(";")){const e=t.split("=");o[e[0]]=e[1]}if(o.DP&&(n.DP=Number.parseInt(o.DP)),o.AD){n.allele2count={};const t=o.AD.split(",");for(const[e,o]of r.entries())n.allele2count[o]=Number.parseInt(t[e])}return n}function Gt(t,e,n){const r=t.sampledata.find((t=>t.sampleobj.name==e));if(r){if(r.AD){const e=r.AD[t.ref]\|\|0,o=r.AD[t.alt]\|\|0,i={chr:t.chr,pos:t.pos,ref:t.ref,alt:t.alt,dnacount:{ref:e,alt:o}};return i.dnacount.f=o+e==0?0:o/(o+e),e+o>=n.dna_mintotalreads&&i.dnacount.f>=n.hetsnp_minbaf&&i.dnacount.f<=n.hetsnp_maxbaf&&(i.dnacount.ishet=!0),i}return null}}async function Ut(t,e,n,r,i){const s=await Wt(u.join(o.tpmasterdir,e.file),n+":"+r+"-"+i),a=new Map;if(s)for(const t of s){const e=t.split("\t"),n=JSON.parse(e[3]),r=Number.parseInt(e[1]),o=Number.parseInt(e[2]);if(a.has(n.name)){const t=a.get(n.name);t.start=Math.min(t.start,r),t.stop=Math.max(t.stop,o)}else a.set(n.name,{gene:n.name,start:r,stop:o,exonunion:[]});const i=a.get(n.name);if(n.exon)for(const t of n.exon){const e=i.exonunion.find((e=>Math.max(e[0],t[0])<Math.min(e[1],t[1])));e?(e[0]=Math.min(t[0],e[0]),e[1]=Math.max(t[1],e[1])):i.exonunion.push([t[0],t[1]])}}for(const[t,e]of a)e.exonlength=e.exonunion.reduce(((t,e)=>t+e[1]-e[0]),0);return a}async function Wt(t,e,n){return new Promise(((r,o)=>{const i=m(vt,[t,e],{cwd:n}),s=[],a=[];i.stdout.on("data",(t=>s.push(t))),i.stderr.on("data",(t=>a.push(t))),i.on("close",(()=>{const t=a.join("");t&&o(t);const e=s.join("").trim();e\|\|r(),r(e.split("\n"))}))}))}function Jt(t,e){return new Promise(((n,r)=>{const o=m(vt,["-H",t],{cwd:e}),i=[],s=[];o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>s.push(t))),o.on("close",(()=>{const t=s.join("");t&&r(t);const e=i.join("").trim();e\|\|r("cannot list vcf meta lines"),n(e.split("\n"))}))}))}function Ht(t,e){const n=e.findIndex((e=>e.value>=t));return-1==n\|\|n==e.length-1?100:0==n?0:Math.ceil(100n/e.length)}function Vt(t,e,n){if(!t.key)return[".key missing"];if(!e.cohort)return["ds.cohort missing"];if(!e.cohort.annotation)return["ds.cohort.annotation missing"];return[null,Promise.resolve().then((()=>{const r=[];for(const o in e.cohort.annotation){if(n&&!n.has(o))continue;const i=e.cohort.annotation[o][t.key];null!=i&&r.push({sample:o,value:i})}return{id:t.id,items:r}}))]}function Yt(t,e,n,i){if(!t.genename)return["genename missing"];const s=t.genename.toLowerCase();if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["gene feature too long (> 10Mb)"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((a,l)=>{const c=[],f=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:f.stdout}).on("line",(t=>{const e=t.split("\t"),n=JSON.parse(e[3]);n.gene&&n.gene.toLowerCase()==s&&n.sample&&(i&&!i.has(n.sample)\|\|c.push(n))}));const d=[];f.stderr.on("data",(t=>d.push(t))),f.on("close",(e=>{const n=d.join("");!n\|\|r(n)?a({id:t.id,items:c}):l(n)}))}))))]}function Qt(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];if(null!=t.valuecutoff&&!Number.isFinite(t.valuecutoff))return["invalid value for valuecutoff"];if(null!=t.focalsizelimit&&!Number.isInteger(t.focalsizelimit))return["invalid value for focalsizelimit"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((s,a)=>{const l=[],c=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:c.stdout}).on("line",(e=>{const n=e.split("\t"),r=JSON.parse(n[3]);r.dt==k.dtcnv&&(t.valuecutoff&&Math.abs(r.value)<t.valuecutoff\|\|(r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2]),t.focalsizelimit&&r.stop-r.start>=t.focalsizelimit\|\|r.sample&&(i&&!i.has(r.sample)\|\|l.push(r))))}));const f=[];c.stderr.on("data",(t=>f.push(t))),c.on("close",(e=>{const n=f.join("");!n\|\|r(n)?s({id:t.id,items:l}):a(n)}))}))))]}function Kt(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];if(null!=t.valuecutoff&&!Number.isFinite(t.valuecutoff))return["invalid value for valuecutoff"];if(null!=t.focalsizelimit&&!Number.isInteger(t.focalsizelimit))return["invalid value for focalsizelimit"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((s,a)=>{const l=[],c=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:c.stdout}).on("line",(e=>{const n=e.split("\t"),r=JSON.parse(n[3]);r.dt==k.dtloh&&(t.valuecutoff&&r.segmean<t.valuecutoff\|\|(r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2]),t.focalsizelimit&&r.stop-r.start>=t.focalsizelimit\|\|r.sample&&(i&&!i.has(r.sample)\|\|l.push(r))))}));const f=[];c.stderr.on("data",(t=>f.push(t))),c.on("close",(e=>{const n=f.join("");!n\|\|r(n)?s({id:t.id,items:l}):a(n)}))}))))]}function Xt(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((s,a)=>{const l=[],c=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:c.stdout}).on("line",(t=>{const e=t.split("\t"),n=JSON.parse(e[3]);n.dt==k.dtitd&&(n.chr=e[0],n.start=Number.parseInt(e[1]),n.stop=Number.parseInt(e[2]),n.sample&&(i&&!i.has(n.sample)\|\|l.push(n)))}));const f=[];c.stderr.on("data",(t=>f.push(t))),c.on("close",(e=>{const n=f.join("");!n\|\|r(n)?s({id:t.id,items:l}):a(n)}))}))))]}function te(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((s,a)=>{const l=[],c=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:c.stdout}).on("line",(t=>{const e=t.split("\t"),n=JSON.parse(e[3]);n.dt!=k.dtsv&&n.dt!=k.dtfusionrna\|\|n.sample&&(i&&!i.has(n.sample)\|\|(n._chr=e[0],n._pos=Number.parseInt(e[1]),n.chrA?(n.chrB=n._chr,n.posB=n._pos):(n.chrA=n._chr,n.posA=n._pos),l.push(n)))}));const f=[];c.stderr.on("data",(t=>f.push(t))),c.on("close",(e=>{const n=f.join("");!n\|\|r(n)?s({id:t.id,items:l}):a(n)}))}))))]}function ee(t,e,n,i){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];return[null,Promise.resolve().then((()=>{if(!n.file)return x.cache_index(n.url,n.indexURL)})).then((e=>new Promise(((s,a)=>{const l=[],c=m(vt,[n.file?u.join(o.tpmasterdir,n.file):n.url,t.chr+":"+t.start+"-"+t.stop],{cwd:e});_.createInterface({input:c.stdout}).on("line",(e=>{const n=e.split("\t"),r=JSON.parse(n[3]);if(r.sample&&(!i\|\|i.has(r.sample))){if(r.dt==k.dtsv\|\|r.dt==k.dtfusionrna){if(r.dt==k.dtsv&&t.sv&&t.sv.hidden)return;if(r.dt==k.dtfusionrna&&t.fusion&&t.fusion.hidden)return;r._chr=n[0],r._pos=Number.parseInt(n[1]),r.chrA?(r.chrB=r._chr,r.posB=r._pos):(r.chrA=r._chr,r.posA=r._pos)}else if(r.dt==k.dtcnv){if(t.cnv&&t.cnv.hidden)return;if(t.cnv&&t.cnv.valuecutoff&&Math.abs(r.value)<t.cnv.valuecutoff)return;if(r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2]),t.cnv&&t.cnv.focalsizelimit&&r.stop-r.start>=t.cnv.focalsizelimit)return}else if(r.dt==k.dtloh){if(t.loh&&t.loh.hidden)return;if(t.loh&&t.loh.valuecutoff&&r.segmean<t.loh.valuecutoff)return;if(r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2]),t.loh&&t.loh.focalsizelimit&&r.stop-r.start>=t.loh.focalsizelimit)return}else{if(r.dt!=k.dtitd)return void console.error("unknown datatype",r.dt);if(t.itd&&t.itd.hidden)return;r.chr=n[0],r.start=Number.parseInt(n[1]),r.stop=Number.parseInt(n[2])}l.push(r)}}));const f=[];c.stderr.on("data",(t=>f.push(t))),c.on("close",(e=>{const o=f.join("");if(o&&!r(o))return void a(o);const i=new Map;for(const t of l)i.has(t.sample)\|\|i.set(t.sample,[]),i.get(t.sample).push(t);n.hideLOHwithCNVoverlap&&Dt(i);const c=[];for(const[t,e]of i)for(const t of e)c.push(t);s({id:t.id,items:c})}))}))))]}function ne(t,e,n,r){if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>1e7)return["look range too big (>10Mb)"];const o=[];for(const i of n)if(i.type==k.tkt.mdsvcf){const[n,s]=re(t,e,i,r);if(n)return[n];o.push(s)}else{if(i.type!=k.tkt.mdssvcnv)return["unsupported track type: "+i.type];{const[e,n]=ee(t,0,i,r);if(e)return[e];o.push(n)}}return[null,Promise.all(o).then((t=>{const e=[];for(const n of t)for(const t of n.items)e.push(t);return{id:t[0].id,items:e}}))]}function re(t,e,n,i){if(!n.tracks)return"tracks[] missing from dsquery";if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>3e6)return["look range too big (>3Mb)"];const s=[];for(const e of n.tracks){const a=Promise.resolve().then((()=>{if(!e.file)return x.cache_index(e.url,e.indexURL)})).then((s=>new Promise(((a,l)=>{const c=[],f=m(vt,[e.file?u.join(o.tpmasterdir,e.file):e.url,(e.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1)],{cwd:s});_.createInterface({input:f.stdout}).on("line",(r=>{if(n.iscustom)c.push(r);else if(e.type==k.mdsvcftype.vcf){const[o,s,a]=q.vcfparseline(r,{nochr:e.nochr,samples:e.samples,info:n.info,format:e.format});for(const e of s)if(e.sampledata&&(k.vcfcopymclass(e,{}),!(t.snvindel&&t.snvindel.excludeclasses&&t.snvindel.excludeclasses[e.class]))){if(i){const t=[];for(const n of e.sampledata)i.has(n.sampleobj.name)&&t.push(n);if(0==t.length)continue;e.sampledata=t}for(const t of e.sampledata)delete t.allele2readcount;delete e._m,delete e.vcf_ID,delete e.name,e.dt=k.dtsnvindel,c.push(e)}}else console.error("type not one of mdsvcftype: "+e.type)}));const d=[];f.stderr.on("data",(t=>d.push(t))),f.on("close",(t=>{const e=d.join("");!e\|\|r(e)?a(c):l(e)}))}))));s.push(a)}return[null,Promise.all(s).then((e=>{const n=[];for(const t of e)for(const e of t)n.push(e);return{id:t.id,items:n}}))]}function oe(t){if(!t.endsWith(".gz"))return["no .gz suffix (file should be compressed by bgzip)"];const e=u.join(o.tpmasterdir,t);return c.existsSync(e)?c.existsSync(e+".tbi")\|\|c.existsSync(e+".csi")?[null,e]:[".tbi/.csi index missing"]:[".gz file not found"]}kt.get(qt+"/cardsjson",(async function(t,e){try{if(t.query.datafile&&t.query.tabixCoord)return new Promise(((n,r)=>{const i=m(vt,[u.join(o.tpmasterdir,t.query.datafile),t.query.tabixCoord]),s=[],a=[];i.stdout.on("data",(t=>s.push(t))),i.stderr.on("data",(t=>a.push(t))),i.on("close",(t=>{""!=a.join("").trim()&&r("error querying bedj file");const o=s.join("").trim();n(e.send({file:o.split("\n")}))}))})).catch((t=>{t.stack&&console.error(t.stack)}));throw"invalid cards request"}catch(t){e.send({error:t.message\|\|t})}})),kt.post(qt+"/mdsjsonform",(async function(t,n){if(!e.features.mdsjsonform)return n.send({error:"This feature is not enabled on this server."});if(t.query.deposit){const e=Math.random().toString(),r=await function(){const t=u.join(o.cachedir,"mdsjsonform");return new Promise(((e,n)=>{c.stat(t,((r,o)=>{if(r){if("ENOENT"==r.code)return void c.mkdir(t,(r=>{r&&n("error creating dir"),e(t)}));n("error checking directory")}else o.isDirectory()?e(t):n('"mdsjsonform" exists but not directory')}))}))}(),i=u.join(r,e);return await x.write_file(i,JSON.stringify(t.query.deposit)),void n.send({id:e})}if(t.query.draw){const e=u.join(o.cachedir,"mdsjsonform",t.query.draw),r=await x.read_file(e);try{const t=JSON.parse(r);n.send({json:t})}catch(t){n.send({error:"Invalid JSON"})}return}n.send({})})),kt.get(qt+"/genomes",(async function(t,n){var r;St(t);try{await c.promises.stat(o.tpmasterdir)}catch(t){let e="Error with TP directory ("+t.code+")";const r=o.maintenance\|\|{};if("start"in r&&"stop"in r&&r.tpMessage){const t=+new Date(r.start),n=+new Date(r.stop),o=+new Date;t<=o&&o<=n&&(e=r.tpMessage)}return void n.send({error:e})}const i={};if(t.query&&t.query.genome)i[t.query.genome]=At(t.query.genome);else for(const t in yt)i[t]=At(t);let s=!1;for(const t in yt)yt[t].blat&&(s=!0);n.send({genomes:i,debugmode:o.debugmode,headermessage:o.headermessage,base_zindex:o.base_zindex,codedate:gt.codedate,launchdate:gt.launchdate,hasblat:s,features:e.features,dsAuth:ft.getDsAuth(t),commonOverrides:o.commonOverrides,targetPortal:o.targetPortal,cardsPath:null===(r=o.cards)\|\|void 0===r?void 0:r.path})})),kt.get(qt+"/getDataset",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.datasets)throw"genomeobj.datasets{} missing";let r;for(const e in n.datasets)if(e.toLowerCase()==t.query.dsname.toLowerCase()){r=n.datasets[e];break}if(!r)throw"invalid dsname";return r.isMds3?e.send({ds:X.client_copy(r,null,null,kt,qt)}):r.isMds?e.send({ds:Tt(r)}):e.send({ds:Mt(r)})}catch(t){e.send({error:t.message\|\|t})}})),kt.all(qt+"/genelookup",pt(yt)),kt.all(qt+"/ntseq",(async function(t,e){try{if(!t.query.coord)throw"coord missing";const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.genomefile)throw"no sequence file available";const r=await x.get_fasta(n,t.query.coord);e.send({seq:r.split("\n").slice(1).join("")})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/pdomain",(function(t,e){try{const n=t.query.genome;if(!n)throw"no genome";const r=yt[n];if(!r)throw"invalid genome "+n;if(!r.proteindomain)return e.send({lst:[]});if(!Array.isArray(t.query.isoforms))throw"isoforms[] missing";const o=[];for(const e of t.query.isoforms){if(r.genomicNameRegexp.test(e))continue;const t=r.proteindomain.getbyisoform.all(e);o.push({name:e,pdomains:t.map((t=>{const n=JSON.parse(t.data);return n.refseq=e,n}))})}e.send({lst:o})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/tkbedj",H(yt)),kt.post(qt+"/tkbedgraphdot",z(yt)),kt.all(qt+"/tkbam",B(yt)),kt.get(qt+"/gdcbam",Z),kt.get(qt+"/gdc_ssms",G.handle_gdc_ssms(yt)),kt.get(qt+"/gdc_filter2topGenes",G.handle_filter2topGenes(yt)),kt.get(qt+"/tkaicheck",U(yt)),kt.get(qt+"/blat",V(yt)),kt.all(qt+"/mds3",Y(yt)),kt.get(qt+"/tkbampile",W),kt.post(qt+"/dsdata",(async function(t,e){try{if(!yt[t.query.genome])throw"invalid genome";if(!t.query.dsname)throw".dsname missing";const n=yt[t.query.genome].datasets[t.query.dsname];if(!n)throw"invalid dsname";const r=[];for(const e of n.queries)if((!t.query.expressiononly\|\|e.isgeneexpression)&&!(t.query.noexpression&&e.isgeneexpression\|\|e.dsblocktracklst))if(e.vcffile){const n=await Ot(e,t);r.push(n)}else{if(!e.makequery)throw"unknow type from one of ds.queries[]";{const o=jt(n,e,t);r.push(o)}}e.send({data:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/tkbigwig",F),kt.post(qt+"/tkld",L(yt)),kt.get(qt+"/tabixheader",(async function(t,e){St(t);try{const[n,r,o]=le(t);if(n)throw n;const i=o?await x.cache_index(r,t.query.indexURL):null,s=await x.get_header_tabix(r,i);e.send({lines:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.all(qt+"/snp",(async function(t,e){try{const n=t.query.genome;if(!n)throw"no genome";const r=yt[n];if(!r)throw"invalid genome";if(!r.snp)throw"snp is not configured for this genome";const o=[];if(t.query.byCoord){if(r.genomicNameRegexp.test(t.query.chr))throw"invalid chr name";if(!Array.isArray(t.query.ranges))throw"ranges not an array";for(const e of t.query.ranges){if(!Number.isInteger(e.start)\|\|!Number.isInteger(e.stop)\|\|e.start<0\|\|e.stop<e.start)throw"invalid start/stop";if(e.stop-e.start>=100)throw"range too big";const n=await x.query_bigbed_by_coord(r.snp.bigbedfile,t.query.chr,e.start,e.stop);for(const e of n){const n=Ct(e);if(t.query.alleleLst){let e=!1;for(const r of t.query.alleleLst)if(r&&!n.alleles.includes(r)){e=!0;break}if(e)continue}o.push(n)}}}else{if(!t.query.byName)throw"unknown query method";if(!Array.isArray(t.query.lst))throw".lst[] missing";for(const e of t.query.lst){if(r.genomicNameRegexp.test(e))continue;const t=await x.query_bigbed_by_name(r.snp.bigbedfile,e);for(const e of t){const t=Ct(e);o.push(t)}}}e.send({results:o})}catch(t){return t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.get(qt+"/clinvarVCF",(async function(t,e){St(t);try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.clinvarVCF)throw"no clinvar for this genome";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos is not integer";if(r<0)throw"pos is not positive integer";if(!t.query.chr)throw"chr missing";{const e=n.chrlookup[t.query.chr.toUpperCase()];if(!e)throw"invalid 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e=N.init_bulk_flag(r.genome);if(!e)throw"init_bulk_flag() failed";if(r.mutationset.length>1&&(e.tpsetname=t.name?t.name:"set"+ ++s),i[Math.random()]=e,t.snvindel){const n=(await x.read_file(u.join(o.tpmasterdir,t.snvindel))).trim().split(/\r?\n/),r=S.parseheader(n[0],e);if(r)throw"snvindel header line error: "+r;for(let t=1;t<n.length;t++)S.parseline(t,n[t],e)}if(t.sv){const n=(await x.read_file(u.join(o.tpmasterdir,t.sv))).trim().split(/\r?\n/),r=C.parseheader(n[0],e,!0);if(r)throw"sv header line error: "+r;for(let t=1;t<n.length;t++)C.parseline(t,n[t],e,!0)}if(t.fusion){const n=(await x.read_file(u.join(o.tpmasterdir,t.fusion))).trim().split(/\r?\n/),r=C.parseheader(n[0],e,!1);if(r)throw"fusion header line error: "+r;for(let t=1;t<n.length;t++)C.parseline(t,n[t],e,!1)}if(t.svjson){const n=(await x.read_file(u.join(o.tpmasterdir,t.svjson))).trim().split(/\r?\n/),[r,i]=j.parseheader(n[0],e);if(r)throw"svjson header line error: "+r;for(let 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r.annotations.files){const n=await x.read_file(u.join(o.tpmasterdir,e));R.tsvParse(n).forEach((e=>{const n=e[t].trim();r.annotations.data[n]\|\|(r.annotations.data[n]=[]),r.annotations.data[n].push(e)}))}}for(const t in i)ie(i[t]);delete r.mutationset,e.send({cohort:r,flagset:i})}catch(t){return void e.send({error:t.message\|\|t})}})),kt.post(qt+"/textfile",(function(t,e){if(!t.query.file)return e.send({error:"no file"});if(ae(t.query.file))return e.send({error:"invalid file name"});const n=u.join(o.tpmasterdir,t.query.file);if(null!=t.query.from){if(!Number.isInteger(t.query.from))return void e.send({error:"invalid value for from"});if(!Number.isInteger(t.query.to))return void e.send({error:"invalid value for to"});const r=[];d(c.createReadStream(n)).on("end",(()=>{e.send({text:r.join("\n")})})).lines.map(String).skip(t.query.from-1).take(t.query.to).forEach((t=>{r.push(t)}))}else c.readFile(n,{encoding:"utf8"},((t,n)=>{t?e.send({error:"error reading 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n=function(t,e){if(!e.cohort)return".cohort missing from ds";if(!e.cohort.hierarchies)return".hierarchies missing from ds.cohort";if(!e.cohort.hierarchies.lst)return".hierarchies.lst[] missing from ds.cohort";const n=e.cohort.hierarchies.lst.find((e=>e.name==t.permanentHierarchy.hierarchyname));if(!n)return"unknown hierarchy "+t.permanentHierarchy.hierarchyname;if(!n.levels)return".levels[] missing in hierarchy "+n.name;const r=n.levels[t.permanentHierarchy.levelidx];if(!r)return"level not found by array idx "+t.permanentHierarchy.levelidx;const o=r.k;return delete t.cohortHiddenAttr,t.cohortOnlyAttr={},t.cohortOnlyAttr[o]={},t.cohortOnlyAttr[o][t.permanentHierarchy.valuekey]=1,null}(t.query,s);if(n)return e.send({error:"permanentHierarchy error: "+n})}const l=[],c={count:0,samples:new Set},f={count:0,samples:new Set};for(const e of t.query.rglst){const n=new Promise(((n,i)=>{const 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if(t.query.cohortHiddenAttr[r][xt]){n=!0;break}}if(n)return}}a.value>0?(c.count++,c.samples.add(a.sample)):a.value<0&&(f.count++,f.samples.add(a.sample));const l=Math.max(e.start,o),u=Math.min(e.stop,i);let d,m;e.reverse?(d=Math.floor((e.stop-u)/h),m=Math.floor((e.stop-l)/h)):(d=Math.floor((l-e.start)/h),m=Math.floor((u-e.start)/h));for(let t=d;t<m;t++)a.value>0?p[t].positive++:a.value<0&&p[t].negative++}));const g=[];l.stderr.on("data",(t=>g.push(t))),l.on("close",(t=>{const e=g.join("");!e\|\|r(e)?n(p):i(e)}))}));l.push(n)}Promise.all(l).then((n=>{const r=t.query.rglst.reduce(((e,n)=>e+n.width+t.query.regionspace),0)-t.query.regionspace,o=g(r,t.query.gain.barheight+t.query.loss.barheight),i=o.getContext("2d"),l={gain:{count:c.count,samplenumber:c.samples.size},loss:{count:f.count,samplenumber:f.samples.size},maxvalue:0};if(c.count+f.count==0)return i.font="15px Arial",i.fillStyle="#aaa",i.textAlign="center",i.textBaseline="middle",i.fillText("No data in view range",r/2,t.query.gain.barheight),l.src=o.toDataURL(),void e.send(l);for(const t of n)for(const e of t)l.maxvalue=Math.max(l.maxvalue,e.positive,e.negative);const u=t.query.maxvalue\|\|l.maxvalue;let d=0;for(const e of n){for(const n of e){if(n.positive){i.fillStyle=t.query.gain.color\|\|"#67a9cf";const e=Math.ceil(t.query.gain.barheightMath.min(u,n.positive)/u),r=t.query.gain.barheight-e;i.fillRect(d,r,1,e)}if(n.negative){i.fillStyle=t.query.loss.color\|\|"#ef8a62";const e=Math.ceil(t.query.loss.barheightMath.min(u,n.negative)/u),r=t.query.gain.barheight;i.fillRect(d,r,1,e)}d++}d+=t.query.regionspace}if(l.src=o.toDataURL(),c.samples.size\|\|f.samples.size){const t=new Set([...c.samples,...f.samples]),[e,n]=function(t,e,n){if(!t.cohort\|\|!t.cohort.annotation\|\|0==n.length)return[null,null];const r=[];for(const e of n){const n=t.cohort.annotation[e];n&&r.push(n)}if(0==r.length)return[null,null];let o,i;if(t.cohort.attributes){o=[];for(const n of t.cohort.attributes.lst){const i={label:n.label,key:n.key};if(n.isNumeric){i.isNumeric=!0;continue}const s=new Map;let a=0;for(const e of r){const r=e[n.key];null!=r?(s.has(r)\|\|s.set(r,new Set),s.get(r).add(e[t.cohort.samplenamekey])):a++}const l=[...s];a&&l.push([xt,a]),l.sort(((t,e)=>e[1]-t[1])),i.values=[];for(const[t,r]of l){const o={name:t,sampleset:r};if(n.values&&n.values[t])for(const e in n.values[t])o[e]=n.values[t][e];e.attributeSummary&&e.attributeSummary[n.key]&&e.attributeSummary[n.key][t]&&(o.totalCount=e.attributeSummary[n.key][t]),i.values.push(o)}o.push(i)}}if(t.cohort.hierarchies){i={};for(const n of t.cohort.hierarchies.lst){const o=E()(y(r,n.levels));o.sum((t=>t.value));const s=[];o.eachBefore((r=>{const o={id:r.data.id,name:r.data.name,label:r.data.full,depth:r.depth};if(r.data.lst){o.sampleset=new Set;for(const e of r.data.lst)o.sampleset.add(e[t.cohort.samplenamekey])}r.children\|\|(o.isleaf=1),e.hierarchySummary&&e.hierarchySummary[n.name]&&(o.totalCount=e.hierarchySummary[n.name][r.id]),s.push(o)})),i[n.name]=s}}return[o,i]}(s,a,[...t]);if(e){for(const t of e)for(const e of t.values){e.gain=0,e.loss=0;for(const t of e.sampleset)c.samples.has(t)&&e.gain++,f.samples.has(t)&&e.loss++;delete e.sampleset}l.attributeSummary=e}if(n){for(const t in n)for(const e of n[t])if(e.sampleset){e.gain=0,e.loss=0;for(const t of e.sampleset)c.samples.has(t)&&e.gain++,f.samples.has(t)&&e.loss++}l.hierarchySummary=n}}e.send(l)})).catch((t=>{e.send({error:t}),t.stack&&console.error(t.stack)}))})),kt.post(qt+"/mdssvcnv",(async function(t,n){let i,s,a,l,f,d,h,p,g;if(t.query.iscustom){if(i=yt[t.query.genome],!i)return n.send({error:"invalid genome"});if(s={},a={iscustom:1,file:t.query.file,url:t.query.url,indexURL:t.query.indexURL,allow_getallsamples:!0},t.query.checkexpressionrank){if(!t.query.checkexpressionrank.file&&!t.query.checkexpressionrank.url)return n.send({error:"no file or url for checkexpressionrank"});a.checkexpressionrank={file:t.query.checkexpressionrank.file,url:t.query.checkexpressionrank.url,indexURL:t.query.checkexpressionrank.indexURL}}if(t.query.checkvcf){let e;try{e=JSON.parse(t.query.checkvcf)}catch(t){return n.send({error:"invalid JSON for VCF object"})}if(!e.file&&!e.url)return n.send({error:"no file or url for custom VCF track"});e.type=k.mdsvcftype.vcf,a.checkvcf={info:e.info,tracks:[e]}}if(t.query.checkrnabam){if(!t.query.checkrnabam.samples)return n.send({error:"samples{} missing from checkrnabam"});let e=0;for(const n in t.query.checkrnabam.samples)e++;if(e>13)return n.send({error:"no more than 13 BAM files allowed"});const r=Bt(t.query.checkrnabam);if(r)return n.send({error:r});a.checkrnabam=t.query.checkrnabam}}else{if(i=yt[t.query.genome],!i)return n.send({error:"invalid genome"});if(!i.datasets)return n.send({error:"genome is not equipped with datasets"});if(s=i.datasets[t.query.dslabel],!s)return n.send({error:"invalid dslabel"});if(t.query.getsample4disco)return function(t,e,n,r){if(t.query.iscustom)return e.send({error:"not for custom track"});if(!r.singlesamplemutationjson)return e.send({error:"singlesamplemutationjson not available for this dataset"});const i=t.query.getsample4disco,s=r.singlesamplemutationjson.samples[i];if(!s)return e.send({error:"no data"});const a=u.join(o.tpmasterdir,s);c.readFile(a,{encoding:"utf8"},((t,n)=>{if(t)return e.send({error:"error getting data for this sample"});e.send({text:n})}))}(t,n,0,s);if(t.query.gettrack4singlesample)return function(t,e,n){const r=t.query.gettrack4singlesample;if(t.query.iscustom)return e.send({error:"no server-side config available for custom track"});if(!n.sampleAssayTrack)return e.send({});return e.send({tracks:n.sampleAssayTrack.samples.get(r)})}(t,n,s);if(t.query.findsamplename)return function(t,e,n){if(t.query.iscustom)return e.send({error:"cannot search sample by name in custom track"});const r=t.query.findsamplename.toLowerCase(),o=[];if(!n.cohort.__samplelst){n.cohort.__samplelst=[];for(const t in n.cohort.annotation)n.cohort.__samplelst.push({name:t,low:t.toLowerCase()})}i(n.cohort.__samplelst);for(const t in n.queries){const e=n.queries[t];if(e.type==k.tkt.mdssvcnv&&e.groupsamplebyattr)for(const t of o){const r=n.cohort.annotation[t.name];if(!r)continue;const o=[];for(const t of e.groupsamplebyattr.attrlst){const e=r[t.k];e&&o.push({k:t.k,kvalue:e})}o.length&&(t.attributes=o,t.grouplabel=o.map((t=>t.kvalue)).join(e.groupsamplebyattr.attrnamespacer))}}if(n.cohort&&n.cohort.sampleAttribute&&n.cohort.sampleAttribute.attributes&&n.cohort.annotation)for(const t of o){const e=n.cohort.annotation[t.name];if(!e)continue;const r=[];for(const t in n.cohort.sampleAttribute.attributes){if(n.cohort.sampleAttribute.attributes[t].clientnoshow)continue;const o=e[t];null!=o&&r.push({k:t,v:o})}r.length&&(t.attr=r)}if(n.sampleAssayTrack)for(const t of o){const e=n.sampleAssayTrack.samples.get(t.name);e&&(t.num_assay_tracks=e.length)}if(n.cohort&&n.cohort.mutation_signature)for(const t in n.cohort.mutation_signature.sets){const e=n.cohort.mutation_signature.sets[t];if(e.samples)for(const t of o)e.samples.map.has(t.name)&&(t.mutation_signature=1)}if(n.singlesamplemutationjson)for(const t of o)n.singlesamplemutationjson.samples[t.name]&&(t.disco=1);return e.send({result:o});function i(t){for(const e of t){if(o.length>10)return;-1!=e.low.indexOf(r)&&(o.find((t=>t.name==e.name))\|\|o.push(e))}}}(t,n,s);if(t.query.assaymap)return async function(t,e,n){try{if(!n.assayAvailability)throw"assay availability not enabled for this dataset";const r=new 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to show expression rank";if(!t.query.sample)throw"sample missing";if(t.query.iscustom){if(n=yt[t.query.genome],!n)throw"invalid genome";if(!t.query.file&&!t.query.url)throw"no file or url for expression data";i={},s={file:t.query.file,url:t.query.url,indexURL:t.query.indexURL}}else{const[e,r,o,a]=Et(t.query);if(e)throw e;if(n=r,i=o,s=a,!s.samples)throw"total samples missing from server config";if(-1==s.samples.indexOf(t.query.sample))throw{nodata:1}}if(s.viewrangeupperlimit&&t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>s.viewrangeupperlimit)throw"zoom in under "+k.bplen(s.viewrangeupperlimit)+" to view data";if(t.query.levelkey){if(!t.query.levelvalue)throw"levelvalue is required when levelkey is used";if(!i.cohort\|\|!i.cohort.annotation)throw".cohort.annotation missing from dataset"}if(!s.file){if(!s.url)throw"file or url missing";return x.cache_index(s.url,s.indexURL)}})).then((e=>{const n=[];for(const l of t.query.rglst)n.push(new Promise(((n,c)=>{const f=m(vt,[s.file?u.join(o.tpmasterdir,s.file):s.url,l.chr+":"+l.start+"-"+l.stop],{cwd:e}),d=_.createInterface({input:f.stdout}),h=new Map;d.on("line",(e=>{const n=e.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],s=Number.parseInt(n[1]),l=Number.parseInt(n[2]);if(r.sample==t.query.sample)return h.has(r.gene)\|\|h.set(r.gene,{chr:o,start:s,stop:l,allvalues:[]}),h.get(r.gene).thisvalue=r.value,void(r.ase&&(h.get(r.gene).ase=r.ase));if(t.query.attributes){const e=i.cohort.annotation[r.sample];if(!e)return;for(const n of t.query.attributes)if(n.k&&n.kvalue&&n.kvalue!=e[n.k])return}a.add(r.sample),h.has(r.gene)\|\|h.set(r.gene,{chr:o,start:s,stop:l,allvalues:[]}),h.get(r.gene).allvalues.push({value:r.value})}));const p=[];f.stderr.on("data",(t=>p.push(t))),f.on("close",(t=>{const e=p.join("");e&&!r(e)&&c({message:e}),n(h)}))})));return Promise.all(n)})).then((t=>{const n=[];for(const e of t)for(const[t,r]of e)null!=r.thisvalue&&(r.allvalues.sort(((t,e)=>t.value-e.value)),r.rank=Ht(r.thisvalue,r.allvalues),delete r.allvalues,r.gene=t,n.push(r));e.send({result:n,samplecount:a.size})})).catch((t=>{t.stack&&console.log(t),t.nodata?e.send({nodata:1}):e.send({error:t.message?t.message:t})}))})),kt.post(qt+"/mdsgeneboxplot",st(yt)),kt.post(qt+"/mdsgenevalueonesample",(async function(t,e){const n=t.query;try{if(!n.sample)throw".sample missing";if(!n.genes)throw".genes[] missing";let r,i,s;if(t.query.iscustom){if(r=yt[n.genome],!r)throw"invalid genome";if(!n.file&&!n.url)throw"no file or url for expression data";i={},s={file:n.file,url:n.url,indexURL:n.indexURL}}else{const[t,e,o,a]=Et(n);if(t)throw t;r=e,i=o,s=a}const a=s.file?null:await x.cache_index(s.url,s.indexURL),l={};let c=!0;for(const t of n.genes){let e;await x.get_lines_bigfile({args:[s.file?u.join(o.tpmasterdir,s.file):s.url,t.chr+":"+t.start+"-"+t.stop],dir:a,callback:r=>{const o=r.split("\t");if(!o[3])return;const i=JSON.parse(o[3]);i.gene==t.gene&&i.sample==n.sample&&(e=i.value)}}),Number.isFinite(e)&&(l[t.gene]=e,c=!1)}c?e.send({nodata:1}):e.send({result:l})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/vcf",(async function(t,e){try{const[n,r,o]=le(t);if(n)throw n;const i=o?await x.cache_index(r,t.query.indexURL):null;if(!t.query.rglst)throw"rglst missing";const s=[];for(const e of t.query.rglst)await x.get_lines_bigfile({args:[r,e.chr+":"+e.start+"-"+e.stop],dir:i,callback:t=>s.push(t)});e.send({linestr:s.join("\n")})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.get(qt+"/vcfheader",(async function(t,e){try{if(!t.query.genome)throw"genome missing";const n=yt[t.query.genome];if(!n)throw"invalid genome";const[r,o,i]=le(t);if(r)throw r;const s=i?await x.cache_index(o,t.query.indexURL):null;e.send({metastr:(await x.get_header_tabix(o,s)).join("\n"),nochr:await x.tabix_is_nochr(o,s,n)})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/translategm",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=t.query.gm;if(!r)throw"missing gm{}";if(!r.chr)throw"gm.chr missing";if(!r.start)throw"gm.start missing";if(!Number.isInteger(r.start))throw"gm.start not integer";if(!r.stop)throw"gm.stop missing";if(!Number.isInteger(r.stop))throw"gm.stop not integer";const o=await x.get_fasta(n,r.chr+":"+(r.start+1)+"-"+r.stop),i=k.fasta2gmframecheck(r,o);e.send({frame:i})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.get(qt+"/hicstat",(async function(t,e){St(t);try{const[n,r,o]=le(t);if(n)throw"illegal file name";o\|\|await x.file_is_readable(r);const i=await it(r,o);e.send({out:i})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/hicdata",(function(t,e){const[n,r,o]=le(t);if(n)return void e.send({error:"illegal file name"});const i=[t.query.nmeth\|\|"NONE",r,t.query.pos1,t.query.pos2,t.query.isfrag?"FRAG":"BP",t.query.resolution],s=m(wt,i),a=_.createInterface({input:s.stdout}),l=[],c=[];let u=0,f=0;a.on("line",(e=>{const n=e.split("\t");if(3!=n.length)return void u++;const r=Number.parseInt(n[0]),o=Number.parseInt(n[1]),i=Number.parseFloat(n[2]);Number.isNaN(r)\|\|Number.isNaN(o)\|\|Number.isNaN(i)?f++:null!=t.query.mincutoff&&i<=t.query.mincutoff\|\|l.push([r,o,i])})),s.stderr.on("data",(t=>c.push(t))),s.on("close",(()=>{const t=c.join("");return t?e.send({error:t}):u?e.send({error:u+" lines have other than 3 fields"}):f?e.send({error:f+" lines have non-numerical values in any of the 3 fields"}):void e.send({items:l})}))})),kt.post(qt+"/samplematrix",(function(t,e){Promise.resolve().then((()=>{const e=yt[t.query.genome];if(!e)throw"invalid genome";let n,r;if(t.query.iscustom){if(!t.query.querykey2tracks)throw"querykey2tracks{} missing for custom dataset";n={queries:{}};for(const e in t.query.querykey2tracks){const r=t.query.querykey2tracks[e];if(!r.type)throw'missing "type" for a data track';if(r.type==k.tkt.mdsvcf){const r=t.query.querykey2tracks[e];r.type=k.mdsvcftype.vcf,n.queries[e]={type:k.tkt.mdsvcf,info:r.info,tracks:[r]}}else if(r.type==k.tkt.mdssvcnv)n.queries[e]=r;else{if(r.type!=k.tkt.mdsexpressionrank)throw"unknown type of data track: "+r.type;n.queries[e]=r}}}else{if(!e.datasets)throw"genome is not equipped with datasets";if(!t.query.dslabel)throw"dslabel missing";if(n=e.datasets[t.query.dslabel],!n)throw"invalid dslabel";if(!n.queries)throw"dataset is not equipped with queries"}if(t.query.sampleset)r=new Set(t.query.sampleset);else if(t.query.limitsamplebyeitherannotation){if(!n.cohort)throw"limitsamplebyeitherannotation but no cohort in ds";if(!n.cohort.annotation)throw"limitsamplebyeitherannotation but no cohort.annotation in ds";r=new Set;for(const e in n.cohort.annotation){const o=n.cohort.annotation[e];for(const n of t.query.limitsamplebyeitherannotation)if(o[n.key]==n.value){r.add(e);break}}}const o=[];for(const e of t.query.features){let t,i=[];if(e.querykey){if(!n.queries)throw"using querykey for a feature but no ds.queries";if(t=n.queries[e.querykey],!t)throw"unknown dsquery by key "+e.querykey}else if(e.querykeylst){if(!n.queries)throw"using querykeylst for a feature but no ds.queries";for(const t of e.querykeylst){const e=n.queries[t];if(!e)throw'unknown key "'+t+'" from querykeylst';i.push(e)}if(0==i.length)throw"no valid keys in querykeylst"}else if(!e.issampleattribute)throw"unknown way to query a feature";if(e.isgenevalue){const[i,s]=Yt(e,n,t,r);if(i)throw"error with isgenevalue: "+i;o.push(s)}else if(e.iscnv){const[i,s]=Qt(e,n,t,r);if(i)throw"error with iscnv: "+i;o.push(s)}else if(e.isloh){const[i,s]=Kt(e,n,t,r);if(i)throw"error with isloh: "+i;o.push(s)}else if(e.isvcf){const[i,s]=re(e,n,t,r);if(i)throw"error with isvcf: "+i;o.push(s)}else if(e.isitd){const[i,s]=Xt(e,n,t,r);if(i)throw"error with isitd: "+i;o.push(s)}else if(e.issvfusion){const[i,s]=te(e,n,t,r);if(i)throw"error with issvfusion: "+i;o.push(s)}else if(e.issvcnv){const[i,s]=ee(e,n,t,r);if(i)throw"error with issvcnv: "+i;o.push(s)}else if(e.ismutation){const[t,s]=ne(e,n,i,r);if(t)throw"error with ismutation: "+t;o.push(s)}else{if(!e.issampleattribute)throw"unknown type of feature";{const[t,i]=Vt(e,n,r);if(t)throw"error with issampleattribute: "+t;o.push(i)}}}return Promise.all(o)})).then((t=>{e.send({results:t})})).catch((t=>{e.send({error:"string"==typeof t?t:t.message}),t.stack&&console.error(t.stack)}))})),kt.get(qt+"/mdssamplescatterplot",(async function(t,e){St(t);try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.cohort)throw"no cohort for dataset";if(!r.cohort.annotation)throw"cohort.annotation missing for dataset";const o=r.cohort.scatterplot;if(!o)throw"scatterplot not 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r=e.samples.map.get(n.sample);if(!r)continue;const s=[];for(const t in e.signatures)r[t]&&s.push({k:t,v:r[t]});s.length&&i.push({key:t,valuename:e.samples.valuename,annotation:s.sort(((t,e)=>e.v-t.v))})}e.send({lst:i})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/mdssurvivalplot",lt(yt)),kt.post(qt+"/fimo",rt.handle_closure(yt)),kt.all(qt+"/termdb",P.handle_request_closure(yt)),kt.all(qt+"/termdb-barsql",D.handle_request_closure(yt)),kt.post(qt+"/singlecell",nt.handle_singlecell_closure(yt)),kt.post(qt+"/massSession",et.save),kt.get(qt+"/massSession",et.get),kt.get(qt+"/isoformbycoord",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!t.query.chr)throw"chr missing";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos must be positive integer";const i=n.tracks.find((t=>t.__isgene));i\|\|reject("no gene track");const s=[];await x.get_lines_bigfile({args:[u.join(o.tpmasterdir,i.file),t.query.chr+":"+r+"-"+r],callback:t=>{const e=t.split("\t")[3];if(!e)return;const r=JSON.parse(e);if(!r.isoform)return;const o={isoform:r.isoform},i=n.genedb.getjsonbyisoform.get(r.isoform);i&&(o.name=JSON.parse(i.genemodel).name,o.isdefault=i.isdefault),s.push(o)}}),e.send({lst:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/ase",(async function(t,e){const n=t.query,r=3e6,i=5e5;try{const t=yt[n.genome];if(!t)throw"invalid genome";if(!n.samplename)throw"samplename missing";if(!n.chr)throw"no chr";if(!n.start\|\|!n.stop)throw"no start/stop";if(!n.rnabarheight)throw"no rnabarheight";if(!n.dnabarheight)throw"no dnabarheight";if(!Number.isInteger(n.barypad))throw"invalid barypad";if(n.rnamax&&!Number.isFinite(n.rnamax))throw"invalid value for rnamax";if(!n.checkrnabam)throw".checkrnabam{} missing";const s=Bt(n.checkrnabam);if(s)throw 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n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.genedb.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const r=n.genedb.get_gene2canonicalisoform.get(t.query.gene);e.send(r)}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.get(qt+"/ideogram",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.genedb.hasIdeogram)throw"ideogram not supported on this genome";if(!t.query.chr)throw".chr missing";const r=n.genedb.getIdeogramByChr.all(t.query.chr);if(!r.length)throw"no ideogram data for this chr";e.send(r)}catch(t){e.send({error:t.message\|\|t})}})),async function(){try{await c.promises.stat(o.tpmasterdir)}catch(t){const e="Error with "+o.tpmasterdir+": "+t.code;if("validate"==process.argv[2])throw e;return void console.log("\n!!! 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missing";try{console.log("Connecting",n.genedb.dbfile),n.genedb.db=x.connect_db(n.genedb.dbfile)}catch(t){throw`Cannot connect genedb: ${n.genedb.dbfile}: ${t}`}n.genedb.getnamebynameorisoform=n.genedb.db.prepare("select name from genes where name=? or isoform=?"),n.genedb.getnamebyisoform=n.genedb.db.prepare("select distinct name from genes where isoform=?"),n.genedb.getjsonbyname=n.genedb.db.prepare("select isdefault,genemodel from genes where name=?"),n.genedb.getjsonbyisoform=n.genedb.db.prepare("select isdefault,genemodel from genes where isoform=?"),n.genedb.getnameslike=n.genedb.db.prepare("select distinct name from genes where name like ? limit 20");const e=ht(n.genedb.db);e.has("genealias")&&(n.genedb.getNameByAlias=n.genedb.db.prepare("select name from genealias where alias=?"),n.genedb.tableSize=n.genedb.db.prepare("select count() from genealias where alias=?")),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 ${t}`).get().size)}if(n.termdbs)for(const r in n.termdbs)dt(n.termdbs[r],e.features),console.log(`${r} 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 x.validate_tabixfile(u.join(o.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=x.connect_db(n.proteindomain.dbfile)}catch(t){throw"Error with "+n.proteindomain.dbfile+": "+t}n.proteindomain.getbyisoform=e.prepare(n.proteindomain.statement)}if(n.snp){if(!n.snp.bigbedfile)throw t+".snp: missing bigBed file";n.snp.bigbedfile=u.join(o.tpmasterdir,n.snp.bigbedfile),await x.file_is_readable(n.snp.bigbedfile)}if(n.clinvarVCF){if(!n.clinvarVCF.file)throw t+".clinvarVCF: VCF file missing";n.clinvarVCF.file=u.join(o.tpmasterdir,n.clinvarVCF.file);try{await x.validate_tabixfile(n.clinvarVCF.file)}catch(t){throw"Error with "+n.clinvarVCF.file+": "+t}if(!n.clinvarVCF.infokey)throw t+".clinvarVCF.infokey missing";if(!n.clinvarVCF.categories)throw t+".clinvarVCF.categories{} missing";{const e=p.execSync(vt+" -H 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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 x.validate_tabixfile(u.join(o.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 e=n.hicdomain.groups[t];if(!e.name)throw".name missing from hicdomain "+t;if(!e.sets)throw".set{} missing from hicdomain "+t;for(const n in e.sets){const r=e.sets[n];if(!r.name)throw".name missing from hicdomain "+t+" > "+n;if(!r.file)throw".file missing from hicdomain "+t+" > "+n;r.file=u.join(o.tpmasterdir,r.file);try{await x.validate_tabixfile(r.file)}catch(t){throw"Error with "+r.file+": "+t}}}}if(n.rawdslst){n.datasets={};for(const e of n.rawdslst){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 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o.whiteListPaths){if(t.startsWith(n)\|\|"!"!=n[0]&&mt(t,n)){e=!1;break}if("!"==n[0]&&!mt(t,n)){e=!0;break}}if(e)return!0}if(n)for(const e of se)if(e===u.extname(t).toLowerCase())return!0;return!1}function le(t,e=!0){let n=null,r=!1;if(t.query.file){if(n=t.query.file,ae(n,e,!1))return["illegal file path"];n=u.join(o.tpmasterdir,n)}else if(t.query.url){if(n=t.query.url,n.includes(" "))return["url must not contain whitespace"];if(n.includes('"')\|\|n.includes("'"))return["url must not contain single or double quotes"];r=!0}return n?[null,n,r]:["file unspecified"]}function ce(t){const e=t.split(/\r?\n/);if(e.length<=1\|\|!e[0])return[null,[]];const n=e[0].split("\t"),r=[];for(let t=1;t<e.length;t++){if("#"==e[t][0])continue;const o=e[t].split("\t"),i={};for(let t=0;t<n.length;t++){const e=o[t];e&&(i[n[t]]=e)}r.push(i)}return[null,r]}async function ue(){const t=await c.promises.readdir(o.cachedir_massSession);try{t.forEach((async t=>{const e=(await c.promises.stat(u.join(o.cachedir_massSession,t))).birthtime,n=new Date,r=new Date(e),i=o.features.massSessionDuration\|\|30;Math.round((n.getTime()-r.getTime())/864e5)>i&&(await c.promises.copyFile(u.join(o.cachedir_massSession,t),u.join(o.cachedir_massSessionTrash,t)),await c.promises.unlink(u.join(o.cachedir_massSession,t)),console.log("File deleted: ",t,e))}))}catch(t){throw`Error: ${t}`}}function fe(t,e){if(t.dbfile)try{console.log("Connecting",t.dbfile),t.newconn=x.connect_db(t.dbfile)}catch(e){throw"Error with "+t.dbfile+": "+e}if(t.snvindel_attributes)for(const e of t.snvindel_attributes)if(e.lst)for(const t of e.lst)t.get=t.get.toString();else e.get=e.get.toString();if(t.cohort){if(t.cohort.levels){if(!Array.isArray(t.cohort.levels))throw"cohort.levels must be array for "+t.genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+t.genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+t.genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+t.genomename+"."+t.label;const e=t.newconn.prepare(t.cohort.fromdb.sql).all();delete t.cohort.fromdb,t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.files){let e=[];for(const n of t.cohort.files){if(!n.file)throw".file missing from one of cohort.files[] for "+t.genomename+"."+t.label;const r=c.readFileSync(u.join(o.tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+t.genomename+"."+t.label;e=[...e,...R.tsvParse(r)]}delete t.cohort.files,t.cohort.raw?t.cohort.raw=[...t.cohort.raw,...e]:t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.tosampleannotation){if(!t.cohort.tosampleannotation.samplekey)throw".samplekey missing from .cohort.tosampleannotation for "+t.genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+t.genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+t.genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=he(n,t,e);if(r)throw'Error parsing a query in "'+t.label+'": '+r}if(t.vcfinfofilter){const e=k.validate_vcfinfofilter(t.vcfinfofilter);if(e)throw t.label+": vcfinfofilter error: "+e}if(t.url4variant)for(const e of t.url4variant){if(!e.makelabel)throw"makelabel() missing for one item of url4variant from "+t.label;if(!e.makeurl)throw"makeurl() missing for one item of url4variant from "+t.label;e.makelabel=e.makelabel.toString(),e.makeurl=e.makeurl.toString()}}async function de(t){const e=u.join(o.cachedir,t);try{await c.promises.stat(e)}catch(t){if("ENOENT"!=t.code)throw"error stating dir";try{await c.promises.mkdir(e)}catch(t){throw"cannot make dir"}}return e}function he(t,e,n){if(!t.name)return".name missing";if(t.dsblocktracklst){if(!Array.isArray(t.dsblocktracklst))return"dsblocktracklst not an array in "+e.label;for(const n of t.dsblocktracklst){if(!n.type)return"missing type for a blocktrack of "+e.label;if(!n.file&&!n.url)return"neither file or url given for a blocktrack of "+e.label}}else if(t.vcffile){const e=p.execSync(vt+" -H "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==e)return"no meta lines in VCF file "+t.vcffile+" of query "+t.name;const[r,i,s,a]=q.vcfparsemeta(e.split("\n"));if(a)return"error parsing VCF meta lines of "+t.vcffile+": "+a.join("; ");t.vcf={vcfid:Math.random().toString(),info:r,format:i,samples:s},t.hlinfo&&(t.vcf.hlinfo=t.hlinfo,delete t.hlinfo),t.infopipejoin&&(t.vcf.infopipejoin=t.infopipejoin,delete t.infopipejoin);const l=p.execSync(vt+" -l "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==l)return"tabix -l found no chromosomes/contigs in "+t.vcffile+" of query "+t.name;t.vcf.nochr=k.contigNameNoChr(n,l.split("\n"));let c=0;if(r)for(const t in r)c++;console.log("Parsed vcf meta from "+t.vcffile+": "+c+" INFO, "+s.length+" sample, "+(t.vcf.nochr?'no "chr"':'has "chr"'))}else{if(!t.makequery)return"do not know how to parse query: "+t.name;if(t.isgeneexpression){if(!t.config)return"config object missing for gene expression query of "+t.name;t.config.maf&&(t.config.maf.get=t.config.maf.get.toString())}}}async function pe(t,e,n){if((t.isMds2\|\|t.isMds3\|\|t.isMds)&&Q(t,n),t.assayAvailability){if(!t.assayAvailability.file)throw".assayAvailability.file missing";if(!t.assayAvailability.assays)throw".assayAvailability.assays[] missing";Object.freeze(t.assayAvailability.assays),t.assayAvailability.samples=new Map;for(const e of c.readFileSync(u.join(o.tpmasterdir,t.assayAvailability.file),{encoding:"utf8"}).trim().split("\n")){const[n,r]=e.split("\t");t.assayAvailability.samples.set(n,JSON.parse(r))}console.log(t.assayAvailability.samples.size+" samples with assay availability ("+t.label+")")}if(t.gene2mutcount){if(!t.gene2mutcount.dbfile)throw".gene2mutcount.dbfile missing";try{console.log("Connecting",t.gene2mutcount.dbfile),t.gene2mutcount.db=x.connect_db(t.gene2mutcount.dbfile),console.log("DB connected for "+t.label+": "+t.gene2mutcount.dbfile)}catch(t){throw"Error connecting db at ds.gene2mutcount.dbfile"}}if(t.sampleAssayTrack){if(!t.sampleAssayTrack.file)throw".file missing from sampleAssayTrack";t.sampleAssayTrack.samples=new Map;let e=0,n=new Set;for(const r of c.readFileSync(u.join(o.tpmasterdir,t.sampleAssayTrack.file),{encoding:"utf8"}).trim().split("\n")){if(!r)continue;if("#"==r[0])continue;const[o,i,s]=r.split("\t");if(!i\|\|!s)continue;if(!t.sampleAssayTrack.samples.has(o)){if(t.cohort&&t.cohort.annotation&&!t.cohort.annotation[o]){n.add(o);continue}t.sampleAssayTrack.samples.set(o,[])}const a=JSON.parse(s);if(!k.tkt[a.type])throw"invalid type from a sample track: "+s;a.name\|\|(a.name=o+" "+i),a.assayName=i,t.sampleAssayTrack.samples.get(o).push(a),e++}console.log(e+" assay-tracks from "+t.sampleAssayTrack.samples.size+" samples ("+t.label+")"),n.size&&console.log("Error: "+n.size+" samples with assay tracks are unannotated: "+[...n].join(" "))}if(t.singlesamplemutationjson){const e=t.singlesamplemutationjson;if(!e.file)throw".file missing from singlesamplemutationjson";e.samples={};let n=0;for(const t of c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim().split("\n")){if(!t)continue;if("#"==t[0])continue;const[r,o]=t.split("\t");r&&o&&(n++,e.samples[r]=o)}console.log(n+" samples for disco plot")}if(t.cohort&&t.cohort.db&&t.cohort.termdb&&await K.init_db(t,kt,qt),t.cohort&&t.cohort.files){if(!Array.isArray(t.cohort.files))throw".cohort.files is not array";if(!t.cohort.tohash)throw".tohash() missing from cohort";if("function"!=typeof t.cohort.tohash)throw".cohort.tohash is not function";if(!t.cohort.samplenamekey)throw".samplenamekey missing";if(t.cohort.annotation={},t.cohort.mutation_signature){const e=t.cohort.mutation_signature;if(!e.sets)throw".mutation_signature.sets missing";for(const n in e.sets){const r=e.sets[n];if(r.name\|\|(r.name=n),!r.signatures)throw".signatures{} missing from a signature set";if(r.samples){if(!r.samples.file)throw".samples.file missing from a signature set";const[e,n]=ce(c.readFileSync(u.join(o.tpmasterdir,r.samples.file),{encoding:"utf8"}).trim());r.samples.map=new Map;for(const e of n){const n=e[t.cohort.samplenamekey];if(!n)throw t.cohort.samplenamekey+" missing in file "+r.samples.file;r.samples.map.set(n,e);for(const t in r.signatures)if(e[t]){const o=Number.parseFloat(e[t]);if(Number.isNaN(o))throw"mutation signature value is not float: "+e[t]+" from sample "+n;r.samples.skipzero&&0==o?delete e[t]:e[t]=o}}}}}if(t.cohort.attributes){if(!t.cohort.attributes.lst)throw".lst[] missing for cohort.attributes";if(!Array.isArray(t.cohort.attributes.lst))return".cohort.attributes.lst is not array";for(const e of t.cohort.attributes.lst){if(!e.key)throw".key missing from one of the .cohort.attributes.lst[]";if(!e.label)throw".label missing from one of the .cohort.attributes.lst[]";if(!e.values)throw".values{} missing from "+e.label+" of .cohort.attributes.lst";for(const t in e.values)if(!e.values[t].label)throw".label missing from one value of "+e.label+" in .cohort.attributes.lst"}if(t.cohort.attributes.defaulthidden)for(const e in t.cohort.attributes.defaulthidden){const n=t.cohort.attributes.lst.find((t=>t.key==e));if(!n)throw"invalid defaulthidden key: "+e;for(const r in t.cohort.attributes.defaulthidden[e])if(!n.values[r])throw"invalid defaulthidden value "+r+" for "+e}}if(t.cohort.hierarchies){if(!t.cohort.hierarchies.lst)throw".lst[] missing from .cohort.hierarchies";if(!Array.isArray(t.cohort.hierarchies.lst))throw".cohort.hierarchies.lst is not array";for(const e of t.cohort.hierarchies.lst){if(!e.name)throw".name missing from one hierarchy";if(!e.levels)throw".levels[] missing from one hierarchy";if(!Array.isArray(e.levels))throw".levels is not array from one hierarchy";for(const t of e.levels)if(!t.k)throw".k missing from one level in hierarchy "+e.name}}if(t.cohort.sampleAttribute){if(!t.cohort.sampleAttribute.attributes)throw"attributes{} missing from cohort.sampleAttribute";for(const e in t.cohort.sampleAttribute.attributes){const n=t.cohort.sampleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from cohort.sampleAttribute.attributes";if(n.values)for(const t in n.values){const e=n.values[t];if("object"!=typeof e)throw'value "'+t+'" not pointing to {} from sampleAttribute';e.name\|\|(e.name=t)}if(n.showintrack&&!n.isinteger&&!n.isfloat)throw n.label+": .showintrack requires .isinteger or .isfloat"}}if(t.cohort.scatterplot){if(!t.cohort.sampleAttribute)throw".sampleAttribute missing but required for .cohort.scatterplot";const e=t.cohort.scatterplot;if(!e.querykey)throw".querykey missing from .cohort.scatterplot";{if(!t.queries)throw".cohort.scatterplot.querykey in use but ds.queries{} missing";const n=t.queries[e.querykey];if(!n)throw"unknown query by .cohort.scatterplot.querykey: "+e.querykey;if(n.type!=k.tkt.mdssvcnv)throw"type is not "+k.tkt.mdssvcnv+" of the track pointed to by .cohort.scatterplot.querykey"}if(e.colorbygeneexpression){if(!e.colorbygeneexpression.querykey)throw"querykey missing from .cohort.scatterplot.colorbygeneexpression";if(!t.queries)throw".cohort.scatterplot.colorbygeneexpression in use but ds.queries{} missing";const n=t.queries[e.colorbygeneexpression.querykey];if(!n)throw"unknown query by .cohort.scatterplot.colorbygeneexpression.querykey: "+e.colorbygeneexpression.querykey;if(!n.isgenenumeric)throw"isgenenumeric missing from the track pointed to by .cohort.scatterplot.colorbygeneexpression.querykey"}if(e.tracks,!e.x)throw".x missing from .cohort.scatterplot";if(!e.x.attribute)throw".attribute missing from .cohort.scatterplot.x";const n=t.cohort.sampleAttribute.attributes[e.x.attribute];if(!n)throw"scatterplot.x.attribute is not defined in sampleAttribute";if(!n.isfloat)throw'scatterplot.x is not "isfloat"';if(!e.y)throw".y missing from .cohort.scatterplot";if(!e.y.attribute)throw".attribute missing from .cohort.scatterplot.y";const r=t.cohort.sampleAttribute.attributes[e.y.attribute];if(!r)throw"scatterplot.y.attribute is not defined in sampleAttribute";if(!r.isfloat)throw'scatterplot.y is not "isfloat"';if(e.colorbyattributes)for(const n of e.colorbyattributes){if(!n.key)throw".key missing from one of scatterplot.colorbyattributes";const e=t.cohort.sampleAttribute.attributes[n.key];if(!e)throw"unknown attribute by key "+n.key+" from scatterplot.colorbyattributes";n.label=e.label,n.values=e.values}}for(const e of t.cohort.files){if(!e.file)throw".file missing from one of .cohort.files";const[n,r]=ce(c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim());if(n)throw'cohort annotation file "'+e.file+'": '+n;console.log(t.label+": "+r.length+" samples loaded from annotation file "+e.file),r.forEach((e=>{for(const n in e){let r;t.cohort.sampleAttribute&&(r=t.cohort.sampleAttribute.attributes[n]),r\|\|t.cohort.termdb&&t.cohort.termdb.termjson&&t.cohort.termdb.termjson.map&&(r=t.cohort.termdb.termjson.map.get(n)),r&&(r.isfloat?e[n]=Number.parseFloat(e[n]):r.isinteger&&(e[n]=Number.parseInt(e[n])))}t.cohort.tohash(e,t)}))}if(t.cohort.annorows=Object.values(t.cohort.annotation),console.log(t.label+": total samples from sample table: "+t.cohort.annorows.length),t.cohort.survivalplot){const e=t.cohort.survivalplot;if(!e.plots)throw".plots{} missing from survivalplot";e.init={plottypes:[]};for(const t in e.plots){const n=e.plots[t];if(!n.name)throw".name missing from survivalplot "+t;if(!n.serialtimekey)throw".serialtimekey missing from survivalplot "+t;if(!n.iscensoredkey)throw".iscensoredkey missing from survivalplot "+t;if(!n.timelabel)throw".timelabel missing from survivalplot "+t;n.key=t,e.init.plottypes.push({key:t,name:n.name,timelabel:n.timelabel})}if(e.samplegroupattrlst){e.init.samplegroupings=[];for(const n of e.samplegroupattrlst){if(!n.key)throw".key missing from an attr of samplegroupattrlst for survival";const r=t.cohort.sampleAttribute.attributes[n.key];if(!r)throw'unknown attribute key "'+n.key+'" from survival samplegroupattrlst';const o=new Map;for(const r in t.cohort.annotation){const i=t.cohort.annotation[r],s=i[n.key];if(null==s)continue;let a=!1;for(const t in e.plots)if(null!=i[e.plots[t].serialtimekey]){a=!0;break}a&&(o.has(s)?o.set(s,o.get(s)+1):o.set(s,1))}if(0==o.size)throw'no value found for "'+n.key+'" from survival samplegroupattrlst';const i=[];for(const[t,e]of o)i.push({value:t,count:e});e.init.samplegroupings.push({key:n.key,label:r.label,values:i})}}}}if(t.mutationAttribute){if(!t.mutationAttribute.attributes)throw"attributes{} missing from mutationAttribute";for(const e in t.mutationAttribute.attributes){const n=t.mutationAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from mutationAttribute.attributes";if(!n.appendto_link&&n.values)for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from mutationAttribute.attributes"}}}if(t.alleleAttribute){if(!t.alleleAttribute.attributes)throw"attributes{} missing from alleleAttribute";for(const e in t.alleleAttribute.attributes){const n=t.alleleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from alleleAttribute.attributes";if(!n.isnumeric){if(!n.values)throw".values{} missing for non-numeric key "+e+" from alleleAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from alleleAttribute.attributes"}}}}if(t.locusAttribute){if(!t.locusAttribute.attributes)throw"attributes{} missing from locusAttribute";for(const e in t.locusAttribute.attributes){const n=t.locusAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from locusAttribute.attributes";if(!n.isnumeric&&!n.appendto_link){if(!n.values)throw".values{} missing for non-numeric key "+e+" from locusAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from locusAttribute.attributes"}}}}if(t.queries)for(const r in t.queries){if(n.remove_queries&&-1!=n.remove_queries.indexOf(r)){delete t.queries[r];continue}const o=t.queries[r];if(n.hide_queries&&-1!=n.hide_queries.indexOf(r)&&(o.hideforthemoment=1),o.istrack){if(!o.type)throw".type missing for track query "+r;if(o.viewrangeupperlimit&&!Number.isInteger(o.viewrangeupperlimit))throw".viewrangeupperlimit should be integer for track query "+r;if(o.type==k.tkt.mdsjunction){const n=ge(o,t,e);if(n)throw r+" (mdsjunction) error: "+n}else if(o.type==k.tkt.mdscnv){const n=be(o,t,e);if(n)throw r+" (mdscnv) error: "+n}else if(o.type==k.tkt.mdssvcnv){const n=_e(o,t,e);if(n)throw r+" (svcnv) error: "+n}else{if(o.type!=k.tkt.mdsvcf)throw"unknown track type for a query: "+o.type+" "+r;{const n=await xe(o,t,e);if(n)throw r+" (vcf) error: "+n}}me(o,t)}else{if(!o.isgenenumeric)throw"unknown type of query from "+r;{const n=we(o,t,e);if(n)throw r+" (genenumeric) error: "+n}}}if(t.track&&await K.init_track(t,e),t.annotationsampleset2matrix){if(!t.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!t.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!t.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!t.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!t.annotationsampleset2matrix.groups)throw".groups{} missing in annotationsampleset2matrix";if("object"!=typeof t.annotationsampleset2matrix.groups)throw"ds.annotationsampleset2matrix.groups{} not an object";for(const e in t.annotationsampleset2matrix.groups){const n=t.annotationsampleset2matrix.groups[e];if(!n.groups\|\|!Array.isArray(n.groups)\|\|0==n.groups.length)throw".groups[] must be nonempty array in "+e;for(const r of n.groups){if(!r.name)throw".name missing from one of .groups[] in "+e;const n=r.matrixconfig;if(!n)throw".matrixconfig missing from one of .groups[] of "+e;if(!n.features)throw".features[] missing from group "+e;if(!Array.isArray(n.features))throw".features[] should be array from group "+e;if(0==n.features.length)throw".features[] zero length from group "+e;for(const r of n.features){if(t.annotationsampleset2matrix.commonfeatureattributes)for(const e in t.annotationsampleset2matrix.commonfeatureattributes)null==r[e]&&(r[e]=t.annotationsampleset2matrix.commonfeatureattributes[e]);if(!r.ismutation)return"unknown feature type from group "+e;if(!r.position)throw"position missing from feature "+JSON.stringify(r)+" from group "+e;if(!r.querykeylst)throw".querykeylst[] missing from ismutation feature from group "+e;if(!Array.isArray(r.querykeylst))throw".querykeylst[] not an array from ismutation feature from group "+e;if(0==r.querykeylst.length)throw".querykeylst[] zero length from ismutation feature from group "+e;for(const n of r.querykeylst)if(!t.queries[n])throw'unknown query key "'+n+'" from ismutation feature of group '+e}if(!n.limitsamplebyeitherannotation)throw".limitsamplebyeitherannotation[] missing from group "+e;if(!Array.isArray(n.limitsamplebyeitherannotation))throw".limitsamplebyeitherannotation[] should be array from group "+e;if(0==n.limitsamplebyeitherannotation.length)throw".limitsamplebyeitherannotation[] zero length from group "+e;for(const t of n.limitsamplebyeitherannotation){if(!t.key)throw"key missing from one of limitsamplebyeitherannotation from group "+e;if(!t.value)throw"value missing from one of limitsamplebyeitherannotation from group "+e}}}delete t.annotationsampleset2matrix.commonfeatureattributes}}function me(t,e){if(t.groupsamplebyattr){t.groupsamplebyattr.key2group=new Map;for(const n in e.cohort.annotation)zt(n,[],t.groupsamplebyattr.key2group,[],e,t)}}function ge(t,e,n){if(t.readcountCutoff&&(!Number.isInteger(t.readcountCutoff)\|\|t.readcountCutoff<1))return"readcountCutoff must be positive integer";let r;if(t.file){const[e,n]=oe(t.file);if(e)return"tabix file error: "+e;t.file=n,r=n}else{if(!t.url)return"no file or url given for mdsjunction "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=i.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");if(r[5]){t.samples=r.slice(5),t.attributeSummary=ye(t.samples,e),t.hierarchySummary=ve(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}if(console.log("(mdsjunction) "+t.name+": "+(t.samples?t.samples.length:0)+" samples, "+(t.nochr?'no "chr"':'has "chr"')),!t.infoFilter)return".infoFilter{} missing";if(!t.infoFilter.lst)return".lst[] missing from .infoFilter";for(const e of t.infoFilter.lst){if(!e.key)return".key missing from one of infoFilter";if(!e.label)return".label missing from one of infoFilter";if(!e.categories)return".categories missing from one of infoFilter";for(const t in e.categories){if(!e.categories[t].label)return".label missing from one category of "+e.label;if(!e.categories[t].color)return".color missing from on category of "+e.label}if(e.hiddenCategories){for(const t in e.hiddenCategories)if(!e.categories[t])return"invalid hidden key "+t+" of "+e.label}else e.hiddenCategories={}}if(!t.singlejunctionsummary)return".singlejunctionsummary missing but is currently required from "+t.name;if(t.singlejunctionsummary.readcountboxplotpercohort){if(!t.singlejunctionsummary.readcountboxplotpercohort.groups)return".groups[] missing from query.singlejunctionsummary.readcountboxplotpercohort for "+t.name;for(const e of t.singlejunctionsummary.readcountboxplotpercohort.groups){if(!e.key)return".key missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups";if(!e.label)return".label missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups"}}}function ye(t,e){if(!(e.cohort&&e.cohort.annotation&&e.cohort.attributes&&t))return;const n={};for(const r of e.cohort.attributes.lst){const o={};for(const t in r.values)o[t]=0;for(const n of t){const t=e.cohort.annotation[n];if(!t)continue;const i=t[r.key];null!=i&&(i in o&&o[i]++)}n[r.key]=o}return n}function ve(t,e){if(!e.cohort\|\|!e.cohort.annotation\|\|!e.cohort.hierarchies\|\|0==t.length)return;const n=[];for(const r of t){const 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i=t.diff_score_plotwidth/(r-o),s=ri-oi,a=p(st.devicePixelRatio,e.canvasheightt.devicePixelRatio),l=a.getContext("2d");t.devicePixelRatio>1&&l.scale(t.devicePixelRatio,t.devicePixelRatio);const c=n.map((t=>t.__tempscore)),u=e.canvasheight/c.length;let f=0;const d=e.stackspace/e.canvasheight;for(const t of c){let e=0;for(const n of t)"alt0"==n?l.fillStyle=Y:"ref"==n?l.fillStyle=nt:"alt1"==n?l.fillStyle=Q:"alt2"==n?l.fillStyle=K:"alt3"==n?l.fillStyle=X:"alt4"==n?l.fillStyle=tt:"alt5"==n&&(l.fillStyle=et),l.fillRect(ie,fu,i,u-du),e+=1;f+=1}return{height:e.canvasheight,width:s,src:a.toDataURL(),read_height:u}}function xt(t,e,n,r){for(const o of n)for(const n of o.segments)if(!(n.ridx!=t\|\|Math.max(n.segstart,e.start)>Math.min(n.segstop,e.stop)))for(const t of n.boxes)if(e.ntwidth>=1){if(("S"==t.opr\|\|"X"==t.opr)&&t.s)for(let e=0;e<t.s.length;e++){const n=t.start+e,o=r.find((t=>t.position==n));if(!o)continue;const i=t.s[e];o[i]=1+(o[i]\|\|0),"S"==t.opr&&o.total++}}else if("S"==t.opr){const n=Math.floor((t.start-e.start)e.ntwidth),o=Math.floor((t.start+t.len-e.start)e.ntwidth);for(let t=n;t<=o;t++){const e=r[t];e&&(e.softclip=1+(e.softclip\|\|0),e.total++)}}}async function kt(t,e){if(!await d.file_not_exist(e))return;if(!t.query.gdcFilePosition)throw".gdcFilePosition missing";const n=t.query.regions,r=t.query.gdcFilePosition.split(".");t.query.regions=[{chr:r[0],start:Number(r[1]),stop:Number(r[2])}],await Gt(t),t.query.regions=n}async function qt(t,e,n,r,o){const i=t.map((t=>t.segments[0].seq)),s=t.map((t=>t.segments[0].qual));let a="",l="";o&&(a+=">seq\n"+o.replace("\n","")+"\n");let c=0;for(const t of i){if(!(c<yt))break;a+=">seq\n"+t.replace("\n","")+"\n",l+=It(s[c].replace("\n",""))+"\n",c+=1}return await function(t,e,n,r,o,i,s,a){return new Promise(((n,l)=>{const c=m(k,["-i","-","-t","DNA","--outfmt=clu","--wrap=5000","--maxnumseq="+(e+1),"--maxseqlen=1000"]),u=[],d=[];f.from(t).pipe(c.stdin),c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>d.push(t))),c.on("error",(t=>{console.log("stderr (clustalo):",d),l(t)})),c.on("close",(t=>{let e=0;const c=[],f={final_read_align:[],qual_r:[],qual_g:[],qual_b:[]};let d=0;for(const t of u.toString().split("\n"))if(t.includes("seq ")){let n=0,l="",u=0,h="";0!=e&&a?h=r.split("\n")[e-1].split(","):a\|\|(h=r.split("\n")[e].split(","));let p="",m="",g="";for(const r of t.replace("seq ",""))if(","!=r){if("-"!=r){if(n+=1,l+=r,0==e&&a)c.push(r);else if(r==c[u]&&a\|\|!a){const t=S(h[n-1]/ft).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}else if(r!=c[u]&&a){const t=E(h[n-1]/ft).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}}else n>0&&n<t.replace(/-/g,"").replace(/,/g,"").replace("seq 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n=["view",e.file];e.gdc_case_id\|\|n.push((e.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop),await d.get_lines_bigfile({isbam:!0,args:n,dir:e.dir,callback:(n,r)=>{if(!(1024&n.split("\t")[1]&&e.drop_pcrduplicates)){if(e.downsample){const t=e.downsample;if(t.pointer++,t.pointer>=t.keep&&t.pointer<t.keep+t.skip)return;t.pointer>=t.keep+t.skip&&(t.pointer=0)}t.lines.push(n)}}})}async function At(t,e){const n=[],r=["depth","-r",(t.nochr?e.chr.replace("chr",""):e.chr)+":"+(e.start+1)+"-"+e.stop,"-g","DUP",t.file\|\|t.url];if(t.drop_pcrduplicates&&(r.push("-G"),r.push("0x400")),await d.get_lines_bigfile({isbam:!0,args:r,dir:t.dir,callback:t=>{const r=t.split("\t"),o=Number.parseInt(r[1])-1,i=Number.parseInt(r[2]);if(e.ntwidth>=1)return void n.push({position:o,total:i});const s=Math.floor((o-e.start)e.ntwidth);n[s]\|\|(n[s]={position:o,sum:0,count:0}),n[s].sum+=i,n[s].count++}}),e.ntwidth<1)for(const t of n)t&&(t.total=t.sum/t.count,delete t.sum,delete t.count);return n}async function Mt(t,e){for(const t of e.regions)t.lines.length>0&&t.ntwidth>=st&&(t.to_checkmismatch=!0,t.referenceseq=await Et(e.genome,t.chr+":"+(t.start+1)+"-"+t.stop));for(const n of t)for(const t of n.segments){const n=e.regions[t.ridx];if(!n.to_checkmismatch)continue;const r=[];for(const e of t.boxes)null!=e.cidx&&"M"==e.opr&&(e.s=t.seq.substr(e.cidx,e.len),Ft(r,n,e,e.s));r.length&&t.boxes.push(...r)}for(const t of e.regions)delete t.to_checkmismatch,delete t.referenceseq}function Tt(t,e){if(!t.asPaired){const n=[];for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=Ct(i,o,t);e&&n.push({x1:e.x1,x2:e.x2,__tempscore:e.tempscore,segments:[e]})}}return n}const n=new Map;for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=Ct(i,o,t);if(!e\|\|!e.qname)continue;const s=n.get(e.qname);s?(s.segments.push(e),s.x2=Math.max(s.x2,e.x2)):n.set(e.qname,{x1:Math.max(e.x1,o.x),x2:Math.min(e.x2,o.x+o.width),__tempscore:e.tempscore,segments:[e]})}}return[...n.values()]}function Ct(t,e,n){const{sam_info:r,tempscore:o,ridx:i,keepallboxes:s,keepmatepos:a,keepunmappedread:l}=t,c=r.trim().split("\t");if(c.length<11)return;const u=c[0],f=c[1],d=Number.parseInt(c[3]),h=c[5],p=c[6],m=c[7],g=Number.parseInt(c[8]),y=c[9],v=c[10];if(Number.isNaN(d)\|\|d<=0)return;const b=d-1,_={qname:u,segstart:b,segstart_original:b,segstop:b,boxes:[],forward:!(16&f),ridx:i,seq:y,qual:v,cigarstr:h,tlen:g,flag:f,tempscore:o};if(function(t,e,n,r,o,i){const s=t.flag;if(!(1&s))return;64&s?t.isfirst=!0:128&s&&(t.islast=!0);if("="!=e&&""!=e&&e!=r.chr)return t.rnext=e,void(t.pnext=n);if(8&s)return void(t.discord_unmapped2=!0);32&s&&!(16&s)&&64&s\|\|16&s&&!(32&s)&&128&s\|\|16&s&&!(32&s)&&64&s\|\|32&s&&!(16&s)&&128&s\|\|(t.discord_orientation=!0,o&&(16&s?32&s?t.discord_orientation_direction="R1R2":n>i&&(t.discord_orientation_direction="R1F2"):32&s?n<i&&(t.discord_orientation_direction="R1F2"):t.discord_orientation_direction="F1F2")),2&s\|\|(t.discord_wrong_insertsize=!0,o&&(t.pnext=n))}(_,p,m,e,a,d),4&f)return l?(_.boxes.push({opr:h,start:b,len:y.length,cidx:0,qual:v}),_.discord_unmapped1=!0,_):void 0;if(""!=h){let t=b,r=0,o=0;for(let n=0;n<h.length;n++){const i=h[n];if(i.match(/[0-9]/))continue;const a=Number.parseInt(h.substring(r,n));if("H"!=i)if("N"==i\|\|"P"==i\|\|"D"==i\|\|(o+=a),r=n+1,"="!=i&&"M"!=i)if("I"!=i)if("N"!=i&&"D"!=i)if("X"!=i)if("S"!=i){if("P"!=i)console.log("unknown cigar: "+i);else if(s\|\|t>e.start&&t<e.stop){const e={opr:"P",start:t,len:a,cidx:o-a};_.boxes.push(e)}}else{const n={opr:i,start:t,len:a,cidx:o-a};0==_.boxes.length?(n.start-=a,(s\|\|Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push(n)):_.boxes.push(n)}else{if(s\|\|Math.max(t,e.start)<Math.min(t+a-1,e.stop)){const e={opr:i,start:t,len:a,cidx:o-a};_.boxes.push(e)}t+=a}else(t>=e.start&&t<=e.stop\|\|t+a-1>=e.start&&t+a-1<=e.stop\|\|s)&&_.boxes.push({opr:i,start:t,len:a}),t+=a;else(s\|\|t>e.start&&t<e.stop)&&ae.ntwidth>=rt&&_.boxes.push({opr:"I",start:t,len:a,cidx:o-a});else(s\|\|Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push({opr:i,start:t,len:a,cidx:o-a}),t+=a;else _.boxes.push({opr:i,start:t,len:a,cidx:o-a}),r=n+1}if(0==_.boxes.length)return void(n&&n.readcount_skipped++);_.segstop=t,_.x1=e.x+e.scale(_.boxes[0].start),_.x2=e.x+e.scale((w=_.boxes,Math.max(...w.map((t=>t.start+t.len)))))}var w;return _}async function jt(t,e,n){const[r,o]=function(t,e){let n=(e.groups.length>1?pt/2:pt)/t;return n>10?[Math.min(15,Math.floor(n)),1]:n>7?[Math.floor(n),1]:n>3?[Math.ceil(n),0]:n>1?[Math.floor(n),0]:[n,0]}(t.stacks.length,e);t.stackheight=r,t.stackspace=o;for(const e of t.regions)e.to_printnt=t.stackheight>7&&e.ntwidth>=7,e.to_qual=e.ntwidth>=ot;if(t.stacks.length&&(t.stackheight>=gt&&n.length<mt?t.returntemplatebox=[]:t.partstack\|\|(t.allowpartstack=!0)),t.stackheight>=at){let e=0;for(const t of n)for(const n of t.segments)e=Math.max(e,n.x2-n.x1);e>.7t.stackheight&&(t.canClipArrowhead=!0)}}function Ot(t,e,n){if(e.asPaired){t.stacks=[];const r=[],o=[];for(const t of n){let n=t.segments[0].ridx;1==t.segments.length\|\|2==t.segments.length&&t.segments[0].ridx==t.segments[1].ridx?(t.x1=Math.max(e.regions[n].x,t.x1),t.x2=Math.min(e.regions[n].x+e.regions[n].width,t.x2),r.push(t)):2==t.segments.length&&t.segments[0].ridx!=t.segments[1].ridx&&(t.x1=t.x1,t.x2=t.x2,o.push(t))}if(r.sort(((t,e)=>t.x1-e.x1)),o.sort(((t,e)=>t.x1-e.x1)),o.length>0){const t=[],e=[],i=o[0];for(const n of r)n.x1<i.x1&&n.x2<i.x1?t.push(n):e.push(n);n=[...t,...o,...e]}for(const r of n){let n=r.segments[0].ridx,o=null;if(!e.variant)for(let i=0;i<t.stacks.length;i++){if(r.x2==e.regions[n].x+e.regions[n].width&&t.stacks[i]<r.x1){o=i,t.stacks[i]=r.x2;break}if(t.stacks[i]+e.stacksegspacing<r.x1){o=i,t.stacks[i]=r.x2;break}}null==o&&(o=t.stacks.length,t.stacks[o]=r.x2),r.y=o}}else{n.sort(((t,e)=>t.x1-e.x1)),t.stacks=[];for(let r=0;r<e.regions.length;r++)for(const o of n)if(o.segments[0].ridx==r){let n=null;if(!e.variant&&!e.sv)for(let i=0;i<t.stacks.length;i++)if(t.stacks[i]+e.stacksegspacing<o.x1&&t.stacks[i]+e.stacksegspacing<e.regions[r].x+e.regions[r].width){n=i,t.stacks[i]=o.x2;break}null==n&&(n=t.stacks.length,t.stacks[n]=o.x2),o.y=n}}return n=function(t,e,n){if(!t.partstack)return e;const r=e.filter((e=>e.y>=t.partstack.start&&e.y<=t.partstack.stop));r.forEach((e=>e.y-=t.partstack.start)),e=r,t.stacks=[];for(let e=t.partstack.start;e<=t.partstack.stop;e++)t.stacks.push(0);return t.returntemplatebox=[],e}(t,n),n}async function Et(t,e){const n=(await d.get_fasta(t,e)).split("\n");return n.shift(),n.join("").toUpperCase()}function Rt(t,e,n){const r=function(t,e,n){const r=[];for(let e=0;e<t.stacks.length;e++)r.push(t.stackheight);if(function(t,e){if(!e.asPaired)return;for(const e of t.regions)if(e.ntwidth<=it)return;t.overlapRP_multirows=!0,t.overlapRP_hlline=t.stackspace>0}(t,n),t.overlapRP_multirows)for(const n of e)n.segments.length<=1\|\|n.segments[0].ridx!=n.segments[1].ridx\|\|(n.height=Pt(n,t.stackheight),r[n.y]=Math.max(r[n.y],n.height));const o=[];let i=t.stackspace;for(const e of r)o.push(i),i+=e+t.stackspace;return t.canvasheight=i,o}(t,e,n);for(const n of e){n.y=r[n.y];for(const e of n.segments){const n=t.regions[e.ridx].to_qual?It(e.qual):null;for(const t of e.boxes)null!=t.cidx&&"H"!=t.opr&&(n&&(t.qual=n.slice(t.cidx,t.cidx+t.len)),"I"==t.opr?t.s=e.seq.substr(t.cidx,t.len):"X"!=t.opr&&"S"!=t.opr\|\|(t.s=e.seq.substr(t.cidx,t.len)),delete t.cidx);delete e.seq,delete e.qual}}}function It(t){if(""==t)return null;const e=[];for(let n=0;n<t.length;n++){const r=t[n].charCodeAt(0)-33;e.push(r)}return e}function Pt(t,e){if(2==t.segments.length){const[n,r]=t.segments;return n.x2>r.x1?(r.shiftdownrow=1,2e):e}console.log("more than 2 segments",t.segments.length);const n=[];for(const e of t.segments){let t=null;for(let r=0;r<n.length;r++)if(n[r]<e.x1){t=r,n[r]=e.x2;break}null==t&&(t=n.length,n[t]=e.x2),e.shiftdownrow=t}return en.length}function Ft(t,e,n,r){for(let o=0;o<r.length;o++){if(n.start+o<e.start\|\|n.start+o>e.stop)continue;const i=r[o];if(e.referenceseq[n.start+o-e.start]!=i.toUpperCase()){const e={opr:"X",start:n.start+o,len:1,s:i,cidx:n.cidx+o};t.push(e)}}}function Lt(t,e,n,r){if(n.returntemplatebox){const t=n.regions[e.segments[0].ridx];let o;if(t.width=n.widths[e.segments[0].ridx],r.asPaired)if(2==e.segments.length)o=e.segments[0].ridx!=e.segments[1].ridx?{qname:e.segments[0].qname,x1:e.x1,x2:e.x2,y1:e.y,y2:e.y+(e.height\|\|n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop))),multi_region:!0}:{qname:e.segments[0].qname,x1:Math.max(t.x,e.x1),x2:Math.min(e.x2,t.width),y1:e.y,y2:e.y+(e.height\|\|n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))};else{const t=e.segments[0],r=n.regions[t.ridx];r.width=n.widths[t.ridx],o={qname:e.segments[0].qname,x1:Math.max(r.x,e.x1),x2:Math.min(e.x2,r.width),y1:e.y,y2:e.y+(e.height\|\|n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))}}else o={qname:e.segments[0].qname,x1:Math.max(t.x,e.x1),x2:Math.min(e.x2,t.x+t.width),y1:e.y,y2:e.y+(e.height\|\|n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))},e.segments[0].isfirst&&(o.isfirst=!0),e.segments[0].islast&&(o.islast=!0);n.returntemplatebox.push(o)}for(let o=0;o<e.segments.length;o++){const i=e.segments[o],s=n.regions[i.ridx];if(s.width=n.widths[i.ridx],0==o){Dt(t,i,e.y,n,r);continue}const a=e.segments[o-1],l=n.regions[a.ridx];if(l.width=n.widths[a.ridx],a.x2<=i.x1\|\|e.segments[0].ridx!=e.segments[1].ridx){Dt(t,i,e.y,n,r);const o=Math.floor(e.y+n.stackheight/2)+.5;if(t.strokeStyle=n.stackheight<=2?J:q,t.setLineDash([5,3]),t.beginPath(),l.x==s.x?(t.moveTo(a.x2,o),t.lineTo(i.x1,o)):l.x<a.x2&&i.x1<s.width&&(t.moveTo(Math.min(a.x2,l.width),o),t.lineTo(Math.max(i.x1,s.x),o)),t.stroke(),n.overlapRP_hlline){const r=a.boxes.reduce(((t,e)=>t.start+t.len>e.start+e.len?t:e));if(r.start+r.len==i.boxes[0].start){t.strokeStyle=H,t.setLineDash([]),t.beginPath();const r=Math.floor(i.x1)+.5;t.moveTo(r,e.y),t.lineTo(r,e.y+n.stackheight),t.stroke()}}}else if(n.overlapRP_multirows){if(Dt(t,i,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=H,t.setLineDash([]),t.beginPath(),l.x<=a.x2&&i.x1<=s.width&&(t.moveTo(Math.max(i.x1,s.x),r),t.lineTo(Math.min(a.x2,l.width),r)),t.stroke()}}else Dt(t,i,e.y,n,r)}null!=e.__tempscore&&x.features.indel_read_alignment_scores&&(t.fillStyle="blue",t.font=n.stackheight+"pt Arial",t.fillText(e.__tempscore,r.regions[0].width-100,e.y+n.stackheight/2))}function Dt(t,e,n,r,o){const i=r.regions[e.ridx];i.width=r.widths[e.ridx];for(const o of e.boxes){const s=i.x+i.scale(o.start);if("P"!=o.opr&&"H"!=o.opr&&"I"!=o.opr)if("D"!=o.opr&&"N"!=o.opr)if(""!=o.opr){if("X"!=o.opr&&"S"!=o.opr){if("M"!=o.opr&&"="!=o.opr)throw"unknown opr at rendering: "+o.opr;if(i.to_qual&&o.qual){let a=s;o.qual.forEach((o=>{e.rnext?t.fillStyle=M(o/ft):e.discord_orientation?t.fillStyle=z(o/ft):e.discord_wrong_insertsize?t.fillStyle=C(o/ft):e.discord_unmapped2?t.fillStyle=L(o/ft):t.fillStyle=S(o/ft),a+i.ntwidth+dt<i.width&&i.x<=a?t.fillRect(a,n,i.ntwidth+dt,r.stackheight):a<i.width&&a+i.ntwidth+dt>=i.width&&i.x<=a?t.fillRect(a,n,i.width-a,r.stackheight):a<=i.x&&a+i.ntwidth+dt>i.x&&t.fillRect(i.x,n,i.ntwidth+dt+a-i.x,r.stackheight),a+=i.ntwidth}))}else o.qual?e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q:i.to_printnt?t.fillStyle="white":e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q,s+o.leni.ntwidth+dt<i.width&&s<i.width&&i.x<s+dt?t.fillRect(s,n,o.leni.ntwidth+dt,r.stackheight):s+o.leni.ntwidth+dt<i.width&&i.x>=s?t.fillRect(i.x,n,o.leni.ntwidth+dt+s-i.x,r.stackheight):s+o.leni.ntwidth+dt>=i.width&&i.x<s?t.fillRect(s,n,i.width-s,r.stackheight):s+o.leni.ntwidth+dt>=i.width&&i.x>=s&&t.fillRect(i.x,n,i.width-s,r.stackheight);if(i.to_printnt){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth(e+.5)&&t.fillText(o.s[e],s+i.ntwidth(e+.5),n+r.stackheight/2)}}else if(i.to_qual&&o.qual){i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial");let e=s;for(let s=0;s<o.qual.length;s++){const a=o.qual[s]/ft;t.fillStyle="S"==o.opr?P(a):E(a),e+i.ntwidth+dt<i.x+i.width&&i.x<=e?t.fillRect(e,n,i.ntwidth+dt,r.stackheight):e<i.x+i.width&&e+i.ntwidth+dt>=i.x+i.width&&i.x<=e?t.fillRect(e,n,i.width+i.x-e,r.stackheight):e<=i.x&&e+i.ntwidth+dt>i.x&&t.fillRect(i.x,n,i.ntwidth+dt+e-i.x,r.stackheight),i.to_printnt&&(o.qual?t.fillStyle="white":t.fillStyle="black",e+i.ntwidth/2<i.width&&e<i.width&&i.x<=e+i.ntwidth/2&&t.fillText(o.s[s],e+i.ntwidth/2,n+r.stackheight/2)),e+=i.ntwidth}}else if(t.fillStyle="S"==o.opr?R:j,s+o.leni.ntwidth+dt<i.width&&i.x<s?t.fillRect(s,n,o.leni.ntwidth+dt,r.stackheight):s+o.leni.ntwidth+dt<i.width&&i.x>=s?t.fillRect(i.x,n,o.leni.ntwidth+dt+s-i.x,r.stackheight):s+o.leni.ntwidth+dt<=i.width&&i.x<s&&t.fillRect(s,n,i.width-s,r.stackheight),i.to_printnt&&!o.qual){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth(e+.5)&&t.fillText(o.s[e],s+i.ntwidth(e+.5),n+r.stackheight/2)}}else{if(i.to_qual&&o.qual){let a=s;o.qual.forEach((o=>{e.discord_unmapped2&&(t.fillStyle=L(o/ft)),t.fillRect(a,n,i.ntwidth+dt,r.stackheight),a+=i.ntwidth}))}else e.discord_unmapped2&&(t.fillStyle=F),t.fillRect(s,n,o.leni.ntwidth+dt,r.stackheight);i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial")}else{"D"==o.opr?t.strokeStyle=W:t.strokeStyle=r.stackheight<=2?J:q,t.setLineDash([]);const e=Math.floor(n+r.stackheight/2)+.5;if(t.beginPath(),t.moveTo(Math.max(s,i.x),e),t.lineTo(Math.min(s+o.leni.ntwidth,i.x+i.width),e),t.stroke(),r.stackheight>lt){const e=Math.max(i.x,s),a=Math.min(i.x+i.width,s+o.leni.ntwidth);if(a-e>=50){const s=Math.min(ct,Math.max(ut,r.stackheight-2));t.font=s+"pt Arial";const l=t.measureText(o.len+" 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i=Math.ceil(e.x2+dt);i<=r.width+n.stackheight/2&&(t.fillStyle="white",t.beginPath(),t.moveTo(i-n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i-n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}else{const i=e.x1;i>=r.x&&(t.fillStyle="white",t.beginPath(),t.moveTo(i+n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i+n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}}(t,e,r,i,n),e.rnext&&(i.to_qual\|\|e.x2-e.x1>=20&&r.stackheight>=7&&(t.font=Math.min(G,Math.max(U,r.stackheight-4))+"pt Arial",t.fillStyle="white",t.fillText((o.nochr?"chr":"")+e.rnext,(e.x1+e.x2)/2,n+r.stackheight/2,e.x2-e.x1)))}function zt(t,e,n,r){for(const[t,n]of e.regions.entries()){if(!n.to_printnt)continue;const e=new Set;for(const o of r)for(const r of o.segments){if(r.ridx!=t)continue;const o=r.boxes.filter((t=>"I"==t.opr));if(o.length)for(const t of o)e.add(n.x+n.scale(t.start))}}for(const n of r)for(const r of n.segments){const o=e.regions[r.ridx],i=r.boxes.filter((t=>"I"==t.opr));if(i.length){t.font=Math.max(G,e.stackheight-2)+"pt Arial";for(const s of i){const i=o.x+o.scale(s.start);s.qual?t.fillStyle=Z(s.qual.reduce(((t,e)=>t+e),0)/s.qual.length/ft):t.fillStyle=B;const a=1==s.s.length?s.s:s.s.length;t.fillText(a,i,n.y+e.stackheight(r.on2ndrow\|\|0)+e.stackheight/2)}}}}async function Bt(t,e,n){const r=It(t.qual),o=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)for(let n=0;n<e.len;n++){t.seq[e.cidx+n];o.push('<td style="background:'+S(r[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>")}const i=[];i.push('<li><span style="background:'+F+';color:white">This segment in template is unmapped</span></li>'),1&t.flag&&i.push("<li>Template has multiple segments</li>"),2&t.flag&&i.push("<li>Each segment properly aligned</li>"),16&t.flag&&i.push("<li>Reverse complemented</li>"),32&t.flag&&i.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&i.push("<li>This is the first segment in the template</li>"),128&t.flag&&i.push("<li>This is the last segment in the template</li>"),256&t.flag&&i.push("<li>Secondary alignment</li>"),512&t.flag&&i.push("<li>Not passing filters</li>"),1024&t.flag&&i.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&i.push("<li>Supplementary alignment</li>");let s={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center">\n\t\t\t <tr style="color:white">${o.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE</span>: ${Math.abs(t.seq.length)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${i.join("")}</ul>`};return t.discord_unmapped2&&(s.unmapped_mate=!0),s}async function $t(t,e,n){const r=t.boxes[0].start,o=t.boxes[t.boxes.length-1],i=o.start+o.len,s=await Et(e,n.chr+":"+(r+1)+"-"+i),a=It(t.qual),l=["<td>Reference</td>"],c=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)if("H"!=e.opr)if("I"!=e.opr)if("D"!=e.opr&&"N"!=e.opr)if("S"!=e.opr)if("M"!=e.opr&&"="!=e.opr&&"X"!=e.opr&&""!=e.opr);else for(let n=0;n<e.len;n++){const o=s[e.start-r+n],i=t.seq[e.cidx+n];l.push("<td>"+o+"</td>"),""==t.qual?c.push('<td style="color:black;background:'+(o.toUpperCase()==i.toUpperCase()?S:E)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+(o.toUpperCase()==i.toUpperCase()?S:E)(a[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>")}else for(let n=0;n<e.len;n++)l.push("<td>"+s[e.start-r+n]+"</td>"),""==t.qual?c.push('<td style="background:'+P(1)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+P(a[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=vt)l.push('<td style="font-size:.8em;opacity:.5;white-space:nowrap">'+e.len+" bp</td>"),c.push('<td style="color:black;white-space:nowrap">-----------</td>');else for(let t=0;t<e.len;t++)l.push("<td>"+s[e.start-r+t]+"</td>"),c.push('<td style="color:black">-</td>');else for(let n=e.cidx;n<e.cidx+e.len;n++)l.push("<td>-</td>"),""==t.qual?c.push('<td style="color:'+B+';background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:'+B+";background:"+S(a[n]/ft)+'">'+t.seq[n]+"</td>");let u=0,f=0,d=[],h=[],p=0;for(const e of t.boxes)u=f,f+=e.len,"S"==e.opr&&(p=1,d.push(u),h.push(f));const m=[];t.rnext&&m.push('<li>Next segment on <span style="background:'+A+'">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:'+T+';color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:'+D+';color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:'+T+';color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:'+D+';color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:'+F+';color:white">Other segment in template is unmapped</span></li>'),1&t.flag&&m.push("<li>Template has multiple segments</li>"),2&t.flag&&m.push("<li>Each segment properly aligned</li>"),16&t.flag&&m.push("<li>Reverse complemented</li>"),32&t.flag&&m.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&m.push("<li>This is the first segment in the template</li>"),128&t.flag&&m.push("<li>This is the last segment in the template</li>"),256&t.flag&&m.push("<li>Secondary alignment</li>"),512&t.flag&&m.push("<li>Not passing filters</li>"),1024&t.flag&&m.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&m.push("<li>Supplementary alignment</li>");let g={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center;font-family:courier">\n\t\t\t <tr style="opacity:.6">${l.join("")}</tr>\n\t\t\t <tr style="color:white">${c.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">CHR</span>: ${n.chr.replace("chr","")},\n\t\t\t<span style="opacity:.5;font-size:.7em">START</span>: ${t.segstart_original+1},\n\t\t\t<span style="opacity:.5;font-size:.7em">STOP</span>: ${i},\n\t\t\t<span style="opacity:.5;font-size:.7em">READ LENGTH</span>: ${t.seq.length} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE LENGTH</span>: ${Math.abs(t.tlen)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${m.join("")}</ul>`,start_readpos:r+1,boxes:t.boxes,readpanel_DN_maxlength:vt};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function Zt(t){const e=i.createHmac("md5",_t),n=[t.get("X-Auth-Token")\|\|t.cookies.sessionid,t.query.gdcFileUUID,t.query.gdcFilePosition];return e.update(n.join("")).digest("hex")+".bam"}async function Gt(t){const e=t.query.regions;if(!Array.isArray(e)\|\|0==e.length)throw"req.query.regions[] not non-empty array";const n=[];for(const r of e){const e=await Ut(r.chr,r.start,r.stop,t.get("X-Auth-Token"),t.query.gdcFileUUID,Zt(t),t.cookies.sessionid);n.push({filesize:e})}return n}async function Ut(t,e,n,r,o,i,s){const f={compression:!1};s?f.Cookie=`sessionid=${s}`:f["X-Auth-Token"]=r;const h=c.join(x.cachedir_bam,i),p=bt+"/slicing/view/"+o+"?region="+t+":"+e+"-"+n;try{if(await d.file_not_exist(h)&&(await l(a.stream(p,{method:"GET",headers:f}),u.createWriteStream(h)),await d.file_not_exist(h)))throw"BAM file slice is not found after downloading";const t=h+".bai";if(await d.file_not_exist(t)&&(await async function(t){await d.get_lines_bigfile({isbam:!0,args:["index",t],callback:()=>{}})}(h),await d.file_not_exist(t)))throw"index file is missing after indexing";const e=await u.promises.stat(h);return _(e.size,!0)}catch(t){throw t.stack&&console.log(t.stack),"Error with BAM slicing: "+(t.message\|\|t)}}t.exports=t=>async(e,n)=>{try{if(delete e.query.isFileSlice,e.query.gdcFileUUID){const t=e.cookies.sessionid,n=e.get("X-Auth-Token");if(!n&&!t)throw"GDC token or sessionid missing";await w(e.query.gdcFileUUID,n,t),e.query.file=Zt(e),e.query.isFileSlice=!0}if(e.query.downloadgdc)return void n.send(await Gt(e));if(e.query.clientdownloadgdcslice){if(!e.query.file\|\|!e.query.isFileSlice)throw"invalid query";const t=c.join(x.cachedir_bam,e.query.file),r=await u.promises.readFile(t);return n.writeHead(200,{"Content-Type":"application/octet-stream","Content-Disposition":"attachment; filename=gdc.bam","Content-Length":r.length}),void n.end(Buffer.from(r,"binary"))}if(!e.query.genome)throw".genome missing";const o=t[e.query.genome];if(!o)throw"invalid genome";if(e.query.getread)return void n.send(await async function(t,e){if(!e.query.chr)throw".chr missing";if(!e.query.qname)throw".qname missing";if(e.query.qname=decodeURIComponent(e.query.qname),!e.query.start)throw".start missing";if(!e.query.stop)throw".stop missing";const n={chr:e.query.chr,start:Number(e.query.start),stop:Number(e.query.stop),scale:()=>{},ntwidth:10};if(!Number.isInteger(n.start))throw".start not integer";if(!Number.isInteger(n.stop))throw".stop not integer";const o=await async function(t,e){let n,o,i,s,a,l,u,f,p;if(t.query.isFileSlice)a=c.join(x.cachedir_bam,t.query.file),await kt(t,a);else{if([s,a,l]=r.fileurl(t),s)throw s;i=l?await d.cache_index(a,t.query.indexURL\|\|a+".bai"):null}if(t.query.unknownorder&&(u=Number(t.query.readstart),f=Number(t.query.readstop),Number.isNaN(u)\|\|Number.isNaN(f)))throw"readstart/stop not provided for read with unknown order";if(await d.get_lines_bigfile({isbam:!0,args:["view",a,(t.query.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+e.start+"-"+e.stop],dir:i,callback:(r,i)=>{if(r.split("\t")[0]!=t.query.qname)return;const s=Ct({sam_info:r,keepallboxes:!0,keepmatepos:!0,keepunmappedread:!0},e);if(s&&(!t.query.show_unmapped\|\|!s.discord_unmapped2))if(t.query.show_unmapped&&t.query.getfirst){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.show_unmapped&&t.query.getlast){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getfirst){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getlast){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.unknownorder){if(s.segstart==u&&s.segstop==f)return i.kill(),void(p=[s])}else if(s.isfirst?n=s:s.islast&&(o=s),n&&o)return i.kill(),void(p=[n,o])}}),p){if(t.query.altseqs){const e={query_seq:p[0].seq,refseqs:t.query.refseqs,altseqs:t.query.altseqs,cigar_seq:p[0].cigarstr,start_position:p[0].segstart,ref_positions:t.query.ref_positions,refalleles:t.query.refalleles,altalleles:t.query.altalleles},n=(await h("align",JSON.stringify(e))).split("\n");let r;for(let t of n)t.includes("Final_output:")?r=JSON.parse(t.replace("Final_output:","")):console.log(t);p.alignments=r}return p}p=[],n&&p.push(n);o&&p.push(o);return p.length?p:null}(e,n);if(!o){if(e.query.show_unmapped)throw"mate not found";throw"read not found"}const i=[];for(const n of o)n.discord_unmapped1?i.push(await Bt(n,t,e.query)):i.push(await $t(n,t,e.query));o.alignments&&(i[0].alignments=o.alignments);return{lst:i}}(o,e));const i=x.debugmode?new Date:null,s=await async function(t,e){let n;if(e.query.isFileSlice)n={genome:t,file:c.join(x.cachedir_bam,e.query.file),asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},await kt(e,n.file);else{const[o,i,s]=r.fileurl(e);if(o)throw o;n={genome:t,file:i,asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},s&&(n.dir=await d.cache_index(i,e.query.indexURL\|\|i+".bai"))}if(e.query.pileupheight&&(n.pileupheight=Number(e.query.pileupheight),Number.isNaN(n.pileupheight)))throw".pileupheight is not integer";e.query.drop_pcrduplicates&&(n.drop_pcrduplicates=!0);if(e.query.variant){n.diff_score_plotwidth=Number(e.query.diff_score_plotwidth),e.query.max_diff_score&&(n.max_diff_score=Number(e.query.max_diff_score),n.min_diff_score=Number(e.query.min_diff_score));const t=e.query.variant.split(".");if(n.strictness=e.query.strictness,!Number.isInteger(t.length%4))throw"invalid variant, not chr.pos.ref.alt";n.alleleAlreadyUpdated=e.query.alleleAlreadyUpdated,n.alleleAlreadyUpdated&&(n.altseqs=e.query.altseqs,n.refseqs=e.query.refseqs,n.altalleles=e.query.altalleles,n.refalleles=e.query.refalleles,n.leftflankseqs=e.query.leftflankseqs,n.rightflankseqs=e.query.rightflankseqs,n.ref_positions=e.query.ref_positions);const r=t.length/4,o=[];for(let e=0;e<r;e++)o.push({chr:t[4e],pos:Number(t[4e+1]),ref:t[4e+2],alt:t[4e+3]});if(n.variant=o,e.query.alignOneGroup&&(n.alignOneGroup=e.query.alignOneGroup),Number.isNaN(n.variant.pos))throw"variant pos not integer"}else if(e.query.sv){const t=e.query.sv.split(".");if(t.length<6)throw"invalid sv, not chrA.posA.chrB.posB";if(n.sv={chrA:t[0],startA:Number(t[1]),strandA:Number(t[2]),chrB:t[3],startB:Number(t[4]),strandB:Number(t[5])},Number.isNaN(n.sv.startA))throw"sv.startA not integer";if(Number.isNaN(n.sv.startB))throw"sv.startB not integer"}if(Number.isFinite(Number(e.query.stackstart))){if(!e.query.stackstop)throw".stackstop missing";if(n.partstack={start:Number(e.query.stackstart),stop:Number(e.query.stackstop)},Number.isNaN(n.partstack.start))throw".stackstart not integer";if(Number.isNaN(n.partstack.stop))throw".stackstop not integer";if(!e.query.grouptype)throw".grouptype required for partstack";n.grouptype=e.query.grouptype}e.query.gdc\|\|(e.query.nochr?n.nochr="string"==typeof e.query.nochr?JSON.parse(e.query.nochr):e.query.nochr:n.nochr=await d.bam_ifnochr(n.file,t,n.dir));if(n.regions=e.query.regions,!Array.isArray(n.regions)\|\|0==n.regions.length)throw"q.regions[] not non-empty array";let o=0;for(const t of n.regions){if(!t.chr)throw".chr missing from a region";if(!Number.isInteger(t.start))throw".start not integer of a region";if(!Number.isInteger(t.stop))throw".stop not integer of a region";t.scale=e=>Math.ceil(t.width(e-t.start)/(t.stop-t.start)),t.ntwidth=t.width/(t.stop-t.start),o=Math.max(o,t.ntwidth)}return n.stacksegspacing=Math.max(2,5o),n.readcount_skipped=0,n}(o,e);n.send(await async function(t){await async function(t){if(t.variant){let e=0,n=0,r=0,o=t.variant[0].pos,i=t.variant[0].pos+Math.max(t.variant[0].ref.length,t.variant[0].alt.length);for(const s of t.variant){const t=Math.abs(s.pos-Math.max(s.ref.length,s.alt.length));t>e&&(e=t,n=r),o>s.pos&&(o=s.pos),i<s.pos+Math.max(s.ref.length,s.alt.length)&&(i=s.pos+Math.max(s.ref.length,s.alt.length)),r+=1}e=Math.floor(1.5Math.max(t.variant[n].ref.length,t.variant[n].alt.length));const s={chr:t.variant[0].chr,start:o-e,stop:i+e};return await Nt(t,[s]),await St(s,t),void(t.regions[0].lines=s.lines)}await Nt(t,t.regions);for(const e of t.regions)await St(e,t)}(t),t.totalnumreads=t.regions.reduce(((t,e)=>t+e.lines.length),0);const e={nochr:t.nochr,count:{r:t.totalnumreads},groups:[]};t.read_limit_reached&&(e.count.read_limit_reached=t.read_limit_reached);t.canvaswidth=t.regions[t.regions.length-1].x+t.regions[t.regions.length-1].width;{const n=await async function(t){const e=[],n=[];let r=0;for(const o of t.regions){for(const t of o.lines)e.push({sam_info:t,tempscore:""});r=o.x+o.width,n.push(r)}if(0==e.length)return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]};if(t.variant){if(1==t.regions.length)return await y(t,e,n);console.log("Indel pipeline works only in single region. Please check!")}if(t.sv&&t.regions.length>1)return async function(t,e,n){const r=v.make_type2group(e),o=[];for(let t=0;t<e.regions.length;t++){const n=e.regions[t],r=(await d.get_fasta(e.genome,n.chr+":"+n.start+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase(),i=[];for(const e of n.lines)i.push({sam_info:e,tempscore:"",ridx:t});const s={refseq:r,start:n.start,stop:n.stop,entries:i};0==t?(s.chr=e.sv.chrA,s.pos=e.sv.startA):1==t?(s.chr=e.sv.chrB,s.pos=e.sv.startB):console.log("More than two regions, please check"),o.push(s)}const i=new Date,s=(await h("sv",JSON.stringify(o))).split("\n"),a=new Date;let l,c;console.log("Time taken to run rust SV pipeline:",a-i,"ms");for(let t of s)t.includes("multi_region_templates:")?l=JSON.parse(t.replace("multi_region_templates:","")):t.includes("single_region_templates:")&&(c=JSON.parse(t.replace("single_region_templates:","")));if(!e.grouptype\|\|"support_sv"==e.grouptype)for(const t of l)r[v.type_supportsv].templates.push(t);if(!e.grouptype\|\|"support_ref"==e.grouptype)for(const t of c)r[v.type_supportref].templates.push(t);const u=[];for(const t in r){const e=r[t];0!=e.templates.length&&(t==v.type_supportsv?1==e.templates.length?e.messages.push({isheader:!0,t:e.templates.length+" read supporting SV/fusion"}):e.messages.push({isheader:!0,t:e.templates.length+" reads supporting SV/fusion"}):t==v.type_supportref&&e.messages.push({isheader:!0,t:e.templates.length+" reads supporting reference allele"}),e.widths=n,u.push(e))}return{groups:u}}(0,t,n);return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]}}(t);t.groups=n.groups,t.variant&&(e.ref_alleles=n.refalleles,e.alt_alleles=n.altalleles,e.allele_positions=n.ref_positions,e.strand_probability=n.strand_probability,e.alternate_forward_count=n.alternate_forward_count,e.reference_forward_count=n.reference_forward_count,e.alternate_reverse_count=n.alternate_reverse_count,e.reference_reverse_count=n.reference_reverse_count,1==n.strand_significance&&(e.strand_significance=!0),t.alleleAlreadyUpdated\|\|(e.refseqs=n.refseqs,e.altseqs=n.altseqs,e.leftflankseqs=n.leftflankseqs,e.rightflankseqs=n.rightflankseqs,e.ref_positions=n.ref_positions,e.refalleles=n.refalleles,e.altalleles=n.altalleles)),Number.isFinite(t.max_diff_score)&&t.variant?(e.max_diff_score=t.max_diff_score,e.min_diff_score=t.min_diff_score):Number.isFinite(n.max_diff_score)&&(e.max_diff_score=n.max_diff_score,e.min_diff_score=n.min_diff_score),n.refalleleerror&&(e.refalleleerror=n.refalleleerror)}if(0==e.count.r)throw"No reads in view range.";if(t.alignOneGroup){const e=t.groups.find((e=>e.type==t.alignOneGroup));if(!e)throw"cannot find group for realignment";let n=Tt(t,e);return n=Ot(e,t,n),await async function(t,e,n){let r;if(e.variant)if("support_ref"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await qt(n,o,t.partstack.start,t.partstack.stop,e.refseqs[0]):await qt(n,o,0,0,e.refseqs[0])}else if("support_no"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await qt(n,o,t.partstack.start,t.partstack.stop):await qt(n,o)}else if("support_amb"==t.type)console.log("Realignment of reads in ambiguous group is not currently implemented");else if(t.type.includes("support_alt")){for(let o=0;o<e.variant.length;o++)if(t.type=="support_alt"+o.toString()){let i=e.leftflankseqs[o].length;r=t.partstack?await qt(n,i,t.partstack.start,t.partstack.stop,e.altseqs[o]):await qt(n,i,0,0,e.altseqs[o])}}else console.log("Unaccounted group, please check");return{alignmentData:r}}(e,t,n)}let n=[];for(const r of t.groups){let o=Tt(t,r);o=Ot(r,t,o),await jt(r,t,o),await Mt(o,t),Rt(r,o,t);const i={type:r.type,width:t.canvaswidth,height:r.canvasheight,stackheight:r.stackheight,stackcount:r.stacks.length,allowpartstack:r.allowpartstack,templatebox:r.returntemplatebox,count:{r:o.reduce(((t,e)=>t+e.segments.length),0)}},s=p(t.canvaswidtht.devicePixelRatio,r.canvasheightt.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio),a.textAlign="center",a.textBaseline="middle",i.messages=r.messages,i.messagerowheights=0;for(const e of o)Lt(a,e,r,t);zt(a,r,t,o),t.asPaired&&(i.count.t=o.length),t.variant&&(i.diff_scores_img=await wt(t,r,o,e.max_diff_score,e.min_diff_score),"support_alt0"==i.type?i.group_color=Y:"support_alt1"==i.type?i.group_color=Q:"support_alt2"==i.type?i.group_color=K:"support_alt3"==i.type?i.group_color=X:"support_alt4"==i.type?i.group_color=tt:"support_alt5"==i.type?i.group_color=et:"support_ref"==i.type&&(i.group_color=nt)),i.src=s.toDataURL(),e.groups.push(i),n=[...n,...o]}t.readcount_skipped&&(e.count.skipped=t.readcount_skipped);t.getcolorscale&&(e.colorscale=function(t){const e=160,n=20,r=1,o=12,i=5,s=100,a=4,l=s+e+10,c=2o+i+a+4(n+r),u=p(t.devicePixelRatiol,t.devicePixelRatioc),f=u.getContext("2d");t.devicePixelRatio>1&&f.scale(t.devicePixelRatio,t.devicePixelRatio);f.fillStyle="black",f.font=o+"pt Arial",f.textAlign="center",f.fillText("Base quality",s+e/2,o);let d=2o+i;function h(t,r,o){const i=s,a=f.createLinearGradient(i,o,i+e,o);a.addColorStop(0,r),a.addColorStop(1,t),f.fillStyle=a,f.fillRect(i,o,e,n)}return f.strokeStyle="black",f.beginPath(),f.moveTo(s,d),f.lineTo(s,d+a),f.moveTo(s+e/4,d),f.lineTo(s+e/4,d+a),f.moveTo(s+e/2,d),f.lineTo(s+e/2,d+a),f.moveTo(s+3e/4,d),f.lineTo(s+3e/4,d+a),f.moveTo(s+e,d),f.lineTo(s+e,d+a),f.closePath(),f.stroke(),f.fillText(40,s,d),f.fillText(30,s+e/4,d),f.fillText(20,s+e/2,d),f.fillText(10,s+3e/4,d),f.fillText(0,s+e,d),f.textAlign="left",f.textBaseline="middle",d+=a,f.fillText("Match",0,d+n/2),h(N,q,d),d+=n+r,f.fillStyle="black",f.fillText("Mismatch",0,d+n/2),h(O,j,d),d+=n+r,f.fillStyle="black",f.fillText("Softclip",0,d+n/2),h(I,R,d),d+=n+r,f.fillStyle="black",f.fillText("Insertion",0,d+n/2),h($,B,d),{width:l,height:c,src:u.toDataURL()}}(t));if(!t.partstack)if(0==e.count.r);else{if(!t.pileupheight)throw"pileupheight missing";e.pileup_data=await async function(t,e){const n=p(t.canvaswidtht.devicePixelRatio,t.pileupheightt.devicePixelRatio),r=n.getContext("2d");t.devicePixelRatio>1&&r.scale(t.devicePixelRatio,t.devicePixelRatio);const o=[];let i=0;for(const[n,r]of t.regions.entries()){o[n]=await At(t,r),xt(n,r,e,o[n]);for(const t of o[n])t&&(i=Math.max(i,t.total))}for(const[e,n]of t.regions.entries()){const s=t.pileupheight/i;for(const i of o[e]){if(!i)continue;const e=(i.position-n.start)n.ntwidth+n.x,o=n.ntwidth>=1?e:Math.floor(e),a=Math.max(1,n.ntwidth);{r.fillStyle=V;const e=i.totals;r.fillRect(o,t.pileupheight-e,a,e)}let l=0;if(i.A){r.fillStyle=b.A;const e=i.As;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.C){r.fillStyle=b.C;const e=i.Cs;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.G){r.fillStyle=b.G;const e=i.Gs;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.T){r.fillStyle=b.T;const e=i.Ts;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.softclip){r.fillStyle=R;const e=i.softclips;r.fillRect(o,t.pileupheight-l-e,a,e)}}}return{width:t.canvaswidth,maxValue:i,src:n.toDataURL()}}(t,n)}return e}(s)),x.debugmode&&console.log("bam.js time ms",new Date-i)}catch(t){n.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}}},8953:(t,e,n)=>{"use strict";n.d(e,{Y:()=>s});n(8171).jStat,n(1017),n(9699).features;const r=n(3856),o=n(1271).run_rust,i=(n(2081).spawn,n(2781).Readable,n(4521),n(2384));n(7147),n(334).clustalo;async function s(t,e,n){const s=t.regions[0].lines[0].split("\t")[9].length;let a=!1,l=[],c=[],u=[],f=[],d=[],h=[],p=[];if(t.alleleAlreadyUpdated)l=t.leftflankseqs,c=t.rightflankseqs,h=t.refseqs,p=t.altseqs,u=t.refalleles,f=t.altalleles,d=t.ref_positions,0!=h[0].toUpperCase().localeCompare((l[0]+u[0]+c[0]).toUpperCase())&&(console.log("Reference allele is not correct for variant 0"),a=!0);else{let e,n,o=0;for(const i of t.variant){let a="",l="";if(!(0!=i.ref.length&&"-"!=i.ref\|\|"-"!=i.alt&&0!=i.alt.length))throw"Both Ref and Alt alleles are missing";if(0==i.ref.length\|\|"-"==i.ref)a=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase(),l=a+i.alt,i.pos-=1;else if("-"==i.alt\|\|0==i.alt.length){const e=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase();a=e+i.ref,l=e,i.pos-=1}else l=i.alt,a=i.ref;const c=i.pos,h=a.toUpperCase(),p=l.toUpperCase();0==o?(e=c-s,n=c+a.length+1+s):(c-s<e&&(e=c-s),c+a.length+1+s>n&&(n=c+a.length+1+s)),u.push(h),f.push(p),d.push(c),o+=1}o=0;for(const i of t.variant){const s=(await r.get_fasta(t.genome,i.chr+":"+e+"-"+d[o])).split("\n").slice(1).join("").toUpperCase(),a=(await r.get_fasta(t.genome,i.chr+":"+(d[o]+u[o].length+1)+"-"+n)).split("\n").slice(1).join("").toUpperCase(),m=s+u[o]+a,g=s+f[o]+a;console.log(i.chr+"."+d[o]+"."+u[o]+"."+f[o]),o+=1,l.push(s),c.push(a),h.push(m),p.push(g)}}const m=[];for(let t=0;t<e.length;t++){const n=e[t].sam_info.split("\t");m.push({read_sequence:n[9],start_position:Number(n[3]),cigar:n[5],flag:Number(n[1])})}const g=[];for(let t=0;t<u.length;t++)g.push({ref_position:Number(d[t]),refallele:u[t],altallele:f[t],refseq:h[t],altseq:p[t],leftflankseq:l[t],rightflankseq:c[t]});Number.isFinite(Number(t.strictness))\|\|(t.strictness=1);const y={reads:m,alleles:g,strictness:Number(t.strictness)},v=new Date,b=await o("indel",JSON.stringify(y)),_=new Date;console.log("Time taken to run rust indel pipeline:",_-v,"ms");const w=b.split("\n");let x,k,q,N,S,A,M=0;for(let t of w)t.includes("Final_output:")?x=JSON.parse(JSON.parse(t.replace("Final_output:",""))):1==u.length&&t.includes("fisher_strand:")?(k=JSON.parse(t.replace("fisher_strand:","")),q=k.alternate_forward_count,N=k.alternate_reverse_count,S=k.reference_forward_count,A=k.reference_reverse_count,M=k.p_value):console.log(t);let T=!1;1==t.variant.length&&M>60&&(T=!0);const C=i.make_type2group(t);t.variant.length;let j=1;for(let n=0;n<x.length;n++){const r=x[n],o=r.read_number,s=r.categories,a=r.categories[0],l=[];if(s.length>1){for(let t=1;t<s.length;t++)l.push(s[t]);s.length-1>j&&(j=s.length-1)}if(a.includes("alt"))for(let n=0;n<t.variant.length;n++)a=="alt"+n.toString()&&C[i.type_supportalt+n.toString()]&&(e[o].tempscore=["alt"+n.toString()],C[i.type_supportalt+n.toString()].templates.push(e[o]));else"ref"==a?C[i.type_supportref]&&(e[o].tempscore=["ref"],C[i.type_supportref].templates.push(e[o])):"none"==a?C[i.type_supportno]&&(e[o].tempscore=l,C[i.type_supportno].templates.push(e[o])):"amb"==a?C[i.type_supportamb]&&(e[o].tempscore=l,C[i.type_supportamb].templates.push(e[o])):console.log("Unaccounted group, please check")}const O=[];for(const e in C){const r=C[e];if(0!=r.templates.length){if(e.includes(i.type_supportalt))for(let n=0;n<t.variant.length;n++)e==i.type_supportalt+n.toString()&&(1==t.variant.length?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the alternative allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the alternative allele"}):1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read support the alternative allele with "+f[n]+" sequence"}):r.messages.push({isheader:!0,t:r.templates.length+" reads support the alternative allele with "+f[n]+" sequence"}));else e==i.type_supportamb?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" ambiguous read"}):r.messages.push({isheader:!0,t:r.templates.length+" ambiguous reads"}):e==i.type_supportref?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the reference allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the reference allele"}):e==i.type_supportno?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting neither reference nor alternative alleles"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting neither reference nor alternative alleles"}):console.log("Unaccounted group, please check");r.widths=n,O.push(r)}}const E=[];for(let t=0;t<O.length;t++)O[t].type.includes("support_alt")&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_ref"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_no"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_amb"==O[t].type&&E.push(O[t]);return{groups:E,refalleleerror:a,ref_positions:d,refalleles:u,altalleles:f,max_diff_score:j,min_diff_score:0,strand_probability:M,strand_significance:T,refseqs:h,altseqs:p,leftflankseqs:l,rightflankseqs:c,alternate_forward_count:q,alternate_reverse_count:N,reference_forward_count:S,reference_reverse_count:A}}},1270:(t,e,n)=>{const r=n(9699),o=n(3856),i=n(6718).createCanvas,s=n(2273).basecolor;t.exports=async(t,e)=>{try{const[n,a,l]=r.fileurl(t);if(n)throw n;let c=t.query.usegrade;const 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o}t.exports=t=>async(e,n)=>{try{const r=e.query,s=t[r.genome];if(!s)throw"unknown genome";let c=null;if(r.file)r.file=o.join(a.tpmasterdir,r.file);else{if(!r.url)throw"file or url missing";c=await i.cache_index(r.url,r.indexURL)}const u=await i.tabix_is_nochr(r.file\|\|r.url,c,s),f=await l(r,c,u);n.send(f)}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message\|\|t})}}},8145:(t,e,n)=>{const r=n(9699),o=(n(1017),n(7147),n(3856)),i=n(6718).createCanvas,s=n(2273).nt2aa,a=n(2818).X,l=400,c="rgba(122,103,44,.7)",u="#edad0c",f="rgba(255,0,0,.5)",d="#ccc";function h(t,e,n,r,o){if(!t)return;if(!o.name&&!o.isoform)return;const i=[];o.name&&i.push(o.name),o.isoform&&i.push(o.isoform),t.push({chr:o.chr,start:o.start,stop:o.stop,x1:e,x2:n,y:r,isoform:o.isoform,name:i.join(" ")})}function p(t,e,n,r,o,i){const s=i/2,a=i/2,l=Math.max(i/2,6);if(o-2s<a)return;const c=Math.ceil((o-2s)/(a+l));if(c<=0)return;const u="+"==e;let f=Math.ceil(n+(o-ac-l(c-1))/2);for(let e=0;e<c;e++)t.beginPath(),u?(t.moveTo(f,r),t.lineTo(f+a,r+i/2),t.moveTo(f+a,r+i/2+1),t.lineTo(f,r+i)):(t.moveTo(f+a,r),t.lineTo(f,r+i/2),t.moveTo(f,r+i/2+1),t.lineTo(f+a,r+i)),t.stroke(),f+=a+l}t.exports=t=>async(e,n)=>{try{n.send(await async function(t,e){const[n,m,g]=r.fileurl(t);if(n)throw n;let y,v,b,_,w;if(t.query.fileIsBigbed=await o.testIfFileIsBigbed(m),t.query.getdata)t.query.getBED;else{if(y=Number(t.query.stackheight),v=Number(t.query.stackspace),b=Number(t.query.regionspace),_=Number(t.query.width),Number.isNaN(y))throw"stackheight is not integer";if(w=Math.max(10,y-2),Number.isNaN(v))throw"stackspace is not integer";if(Number.isNaN(b))throw"regionspace is not integer";if(Number.isNaN(_))throw"width is not a number"}if(t.query.usevalue){if(!t.query.usevalue.key)throw".key missing from 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t){const t=e.split("\t"),n=a(t);n.chr=t[0],n.start=Number(t[1]),n.stop=Number(t[2]),n.rglst=[{idx:r}],c.push(n)}}else await o.get_lines_bigfile({args:[e,i.chr+":"+i.start+"-"+i.stop],dir:n,callback:e=>{const n=e.split("\t");let o={};if(t.getBED)o.rest=n.slice(3);else if(n[3])try{o=JSON.parse(n[3])}catch(t){return void(s=e)}o.chr=n[0],o.start=Number(n[1]),o.stop=Number(n[2]),o.rglst=[{idx:r}],c.push(o)}});l.push(c)}if(s)throw"Line with invalid JSON: "+s;return l}(t.query,m,M,k,q);let C;t.query.filterByName&&(C=new Set(t.query.filterByName.split(/[\s\n]/).map((t=>t.trim()))));const j=[];for(const e of T)for(const n of e){if(t.query.usevalue){const e=n[t.query.usevalue.key];if(!Number.isFinite(e))continue;if(t.query.usevalue.dropBelowCutoff&&e<t.query.usevalue.dropBelowCutoff)continue}if(!(t.query.bplengthUpperLimit&&n.stop-n.start>t.query.bplengthUpperLimit)){if(C)if(n.isoform){if(!C.has(n.isoform))continue}else{if(!n.name)continue;if(!C.has(n.name))continue}j.push(n)}}if(t.query.getdata)return{items:j};if(0==j.length){const e=i(_t.query.devicePixelRatio,yt.query.devicePixelRatio),n=e.getContext("2d");return t.query.devicePixelRatio>1&&n.scale(t.query.devicePixelRatio,t.query.devicePixelRatio),n.font=y+"px Arial",n.fillStyle="#aaa",n.textAlign="center",n.textBaseline="middle",n.fillText("No data in view range",_/2,y/2),{src:e.toDataURL(),height:y}}const O=Math.ceil(y/4)-1;if(N\|\|j.length>=600){const e=j.length<200,n=i(_t.query.devicePixelRatio,yt.query.devicePixelRatio),r=n.getContext("2d");t.query.devicePixelRatio>1&&r.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);const o=j.length<=200?[]:null;for(const n of 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t=i+s.scale(s.reverse?l:a),e=i+s.scale(s.reverse?a:l);null==n?(n=t,r=e):(n=Math.min(n,t),r=Math.max(r,e))}}if(null==n)continue;e.canvas={start:n,stop:r,stranded:null!=e.strand},e.coding&&I&&(e.willtranslate=!0,F.push(e));let o=n,i=r;if(z){const t=e.name;if(t){e.canvas.namestr=t;const n=D.measureText(t).width;e.canvas.namewidth=n,Z?e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):n>e.canvas.stop-e.canvas.start?e.canvas.start>_-e.canvas.stop?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):(e.canvas.namehover=!0,e.canvas.textalign="left"):Math.min(_,e.canvas.stop)-Math.max(0,e.canvas.start)>=n+20?e.canvas.namein=!0:e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):e.canvas.namein=!0}}e.canvas.stop-e.canvas.start>.3_&&(W=[]);for(let 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Set;if(s.cnv\|\|s.loh\|\|s.sv\|\|s.fusion\|\|s.itd){if(!l)throw"no svcnv found in ds.queries";if(r)return await f(l,o,e,!0);const t=await f(l,o,e);for(const e of t)c.add(e)}if(s.snvindel){if(!a)throw"no vcf found in ds.queries";for(const t of a.tracks)await d(a,t,o,c,e)}return t.filter((t=>c.has(t.name)))}async function f(t,e,n,a){const l=n.samplerule.set,c=t.url?await o.cache_index(t.url,t.indexURL):null,u=new Set,f=new Set,d=new Set;return await o.get_lines_bigfile({args:[t.file?r.join(s.tpmasterdir,t.file):t.url,(t.nochr?l.chr.replace("chr",""):l.chr)+":"+l.start+"-"+(l.stop+1)],dir:c,callback:t=>{const n=t.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),s=JSON.parse(n[3]);if(e.has(s.sample)){if(s.dt==i.dtcnv){if(!l.cnv)return;if(l.cnv.focalsizelimit&&o-r>=l.cnv.focalsizelimit)return;if(l.cnv.valuecutoff&&Math.abs(s.value)<l.cnv.valuecutoff)return;return a?s.value>0?u.add(s.sample):f.add(s.sample):d.add(s.sample),void 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t.selectCohort.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=t.selectCohort.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';if(!t.selectCohort.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(t.selectCohort.values))throw"termdb.selectCohort.values is not array";if(0==t.selectCohort.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const e of t.selectCohort.values){if(!e.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(e.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==e.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}if(t.restrictAncestries){if(!Array.isArray(t.restrictAncestries)\|\|0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCfile)e.pcs=await h(e.PCfile,e.PCcount);else if(e.PCfileBySubcohort)for(const t in e.PCfileBySubcohort){const n=e.PCfileBySubcohort[t];if(!n.file)throw".file missing for a subcohort in PCfileBySubcohort";n.pcs=await h(n.file,e.PCcount)}}}}(t.cohort.termdb),await async function(t){if("scatterplots"in t)for(const e of t.scatterplots.plots){const t=r.join(a.tpmasterdir,e.file);await o.file_is_readable(t)}}(t.cohort),i(t),function(t){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[r]=t.sampleId2Name.get(+r);return n}}(t);const{mayGetGeneVariantData:f,getTermTypes:d,mayGetMatchingGeneNames:p}=n(7833);t.mayGetGeneVariantData=f,t.getTermTypes=d,t.mayGetMatchingGeneNames=p,null!==(c=t.cohort)&&void 0!==c&&null!==(u=c.db)&&void 0!==u&&u.refresh&&e&&l(t,e,s)}async function f(t,e){if(!t.track)throw"no mds2 track; missing ds.track{}";const n=t.track;n.name\|\|(n.name=t.label),function(t){if(!t.populations)return;if(!Array.isArray(t.populations))throw"populations should be array";for(const e of t.populations){if(!e.key)throw"key missing from a population";if(e.label\|\|(e.label=e.key),!Array.isArray(e.sets))throw".sets is not an array in population: "+e.key;for(const t of e.sets){if(!t.infokey_AC)throw"infokey_AC missing from a set of population: "+e.key;if(!t.infokey_AN)throw"infokey_AN missing from a set of population: "+e.key;if(e.termfilter&&!t.termfilter_value)throw"termfilter_value missing from a set of population where termfilter is set: "+e.key}}}(n),await async function(t,e,n){if(!t)return;if(!t.chr2bcffile)throw"vcftk.chr2bcffile is missing";{if("object"!=typeof t.chr2bcffile)throw"chr2bcffile not an object";for(const e in t.chr2bcffile)t.chr2bcffile[e]=r.join(a.tpmasterdir,t.chr2bcffile[e]);const n={file:t.chr2bcffile[e.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await o.init_one_vcf(n,e,!0),t.info=n.info,t.format=n.format,t.samples=n.samples,t.nochr=n.nochr}if(t.AD&&t.AD.chr2bcffile){if("object"!=typeof t.AD.chr2bcffile)throw"AD.chr2bcffile not an object";for(const e in t.AD.chr2bcffile)t.AD.chr2bcffile[e]=r.join(a.tpmasterdir,t.AD.chr2bcffile[e]);const i={file:t.AD.chr2bcffile[e.defaultcoord.chr]};if(!i.file)throw"default chr missing from AD.chr2bcffile";await o.init_one_vcf(i,e,!0),t.AD.info=i.info,t.AD.format=i.format,t.AD.samples=i.samples,t.AD.nochr=i.nochr,console.log(n.label+" vcf: AD: "+t.AD.samples.length+" samples");for(const e of t.AD.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}}if(t.samples){for(const e of t.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}console.log(n.label+" vcf: "+t.samples.length+" samples")}else console.log(n.label+" vcf: no samples");if(t.numerical_axis&&t.numerical_axis.info_keys){if(!Array.isArray(t.numerical_axis.info_keys))throw"numerical_axis.info_keys should be an array";for(const e of t.numerical_axis.info_keys){const n=t.info[e.key];if(!n)throw'INFO field "'+e.key+'" not found for numerical_axis';if("Float"!=n.Type&&"Integer"!=n.Type)throw'INFO field "'+e.key+'" from numerical_axis not of integer or float type';if("1"!=n.Number&&"A"!=n.Number)throw'for numerical axis, INFO field "'+e.key+'" only allows to be Number=1 or Number=A'}}if(t.plot_mafcov){if(!t.AD)throw".plot_mafcov enabled but .AD{} missing from vcf";if(!t.AD.samples)throw".plot_mafcov enabled but no samples from vcf";if(!t.AD.format)throw".plot_mafcov enabled but no FORMAT fields from vcf";if(!t.AD.format.AD)throw".plot_mafcov enabled but the AD FORMAT field is missing";if("R"!=t.AD.format.AD.Number)throw"AD FORMAT field Number=R is not true";if("Integer"!=t.AD.format.AD.Type)throw"AD FORMAT field Type=Integer is not true";if(t.plot_mafcov.overlay_term){if(!n.cohort)throw"ds.cohort missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb)throw"ds.cohort.termdb missing when plot_mafcov.overlay_term defined";if(!n.cohort.termdb.q)throw"ERR: termdb.q{} missing while trying to access termdb helper functions";if(!n.cohort.termdb.q.termjsonByOneid)throw"ERR: q.termjsonByOneid missing";const e=n.cohort.termdb.q.termjsonByOneid(t.plot_mafcov.overlay_term);if(!e)throw'unknown term id "'+t.plot_mafcov.overlay_term+'" from vcftk.plot_mafcov.overlay_term';t.plot_mafcov.overlay_term=e}}if(t.termdb_bygenotype){if(!t.samples)throw".termdb_bygenotype enabled but no samples from vcf";if(!t.format)throw".termdb_bygenotype enabled but no FORMAT fields from vcf";if(!t.format.GT)throw".termdb_bygenotype enabled but the GT FORMAT field is missing";if(!n.cohort)throw"termdb_bygenotype but ds.cohort missing";if(!n.cohort.termdb)throw"termdb_bygenotype but ds.cohort.termdb missing";if(t.termdb_bygenotype.getAF){if(!t.termdb_bygenotype.termid_sex)throw"termid_sex missing for getAF at termdb_bygenotype";if(!t.termdb_bygenotype.value_male)throw"value_male missing for getAF at termdb_bygenotype";const e=n.cohort.termdb.q.getSample2value(t.termdb_bygenotype.termid_sex);t.termdb_bygenotype.male_samples=new Set;for(const n of e)n.value==t.termdb_bygenotype.value_male&&t.termdb_bygenotype.male_samples.add(n.sample);if(!t.termdb_bygenotype.sex_chrs)throw"sex_chrs missing for getAF at termdb_bygenotype";if(!Array.isArray(t.termdb_bygenotype.sex_chrs))throw"sex_chrs is not array";t.termdb_bygenotype.sex_chrs=new Set(t.termdb_bygenotype.sex_chrs)}}if(t.samples){t.sample2arrayidx=new Map;for(const[e,n]of t.samples.entries())t.sample2arrayidx.set(n.name,e)}}(n.vcf,e,t),function(t){if(!t.info_fields)return;if(!Array.isArray(t.info_fields))throw"tk.info_fields is not array";for(const e of t.info_fields){if(!e.key)throw".key missing from one of tk.info_fields[]";if(t.vcf&&t.vcf.info&&!t.vcf.info[e.key])throw`info field ${e.key} missing from tk.vcf.info{}`;if(e.label\|\|(e.label=e.key),e.iscategorical){if(!Array.isArray(e.values))throw".values[] not an array of categorical INFO field: "+e.key;for(const t of e.values){if(!t.key)throw"key missing from a value of categorical INFO: "+e.key;t.label\|\|(t.label=t.key)}}else if(e.isfloat\|\|e.isinteger){if(!e.range)throw".range{} missing from a numerical INFO: "+e.key;s(e.range,"tk.info_fields[]")}else if(!e.isflag)throw"tk.info_fields unknown type: "+e.key}}(n),await async function(t,e,n){if(!t)return;if(!Array.isArray(t.tracks))throw"ld.tracks[] not an 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e=["cnv.cnv_change","cnv.gene_level_cn","cnv.consequence.gene.symbol","case.submitter_id","case.case_id"];function n(t){const n=e.slice();if(t.twLst)for(const e of t.twLst){let t=e.term.id;t.startsWith("case.")&&(t="occurrence."+t),n.push(t)}return n.join(",")}function o(t){if(!t.gene&&"string"!=typeof t.gene)throw"p.gene does not provide non-empty string";const e={op:"and",content:[]};return t.gene&&e.content.push({op:"=",content:{field:"cnv.consequence.gene.symbol",value:t.gene.split(",")}}),t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push((0,u.P)("string"==typeof t.filterObj?JSON.parse(t.filterObj):t.filterObj)),e}t.queries.geneCnv.bygene.get=async t=>{var e;const i=S(t),a=await s().post(l().join(f,"cnv_occurrences"),{headers:i,body:JSON.stringify({size:1e5,fields:n(t),filters:o(t)})}),c=JSON.parse(a.body);if(!Array.isArray(null==c\|\|null===(e=c.data)\|\|void 0===e?void 0:e.hits))throw"geneCnv response body is not {data:hits[]}";const u={ssm_id:"geneCnvGain",dt:r.dtcnv,class:r.mclasscnvgain,samples:[]},d={ssm_id:"geneCnvLoss",dt:r.dtcnv,class:r.mclasscnvloss,samples:[]};for(const e of c.data.hits){if("object"!=typeof e.cnv)throw"hit.cnv{} not obj";if("object"!=typeof e.case)throw"hit.case{} not obj";if(!e.cnv.gene_level_cn)throw"hit.cnv.gene_level_cn is not true";let n;if("Gain"==e.cnv.cnv_change)n=u;else{if("Loss"!=e.cnv.cnv_change)throw"hit.cnv.cnv_change is not Gain/Loss";n=d}const r={sample_id:e.case.case_id,__sampleName:e.case.submitter_id};if(t.twLst)for(const n of t.twLst)A(r,e.case,n);n.samples.push(r)}const h=[];return u.samples.length&&h.push(u),d.samples.length&&h.push(d),h}}function N(t,e){if(!e)return;const n=e.split(",");for(const e of n){const n=e.split("--");if(2==n.length)return t.geneA=n[0].split("(")[0],void(t.geneB=n[1].split("(")[0])}}function S(t){const e={"Content-Type":"application/json",Accept:"application/json"};return t&&(t.token&&(e["X-Auth-Token"]=t.token),t.sessionid&&(e.Cookie="sessionid="+t.sessionid)),e}function A(t,e,n){const r=n.term.id.split(".");if(function e(o,i){const s=r[i];if(i==r.length-1)return void(t[n.term.id]?t[n.term.id].add(o[s]):t[n.term.id]=o[s]);const a=o[s];if(null==a)return;if(Array.isArray(a)){t[n.term.id]=new Set;for(const t of a)e(t,i+1);return}e(a,i+1)}(e,1),t[n.term.id]instanceof Set&&(t[n.term.id]=[...t[n.term.id]][0]),n.term.id in t&&"categorical"==n.term.type){const e=function(t,e){var n,r,o,i,s,a,l;if("custom-groupset"==(null===(n=e.q)\|\|void 0===n?void 0:n.type)&&Array.isArray(null===(r=e.q)\|\|void 0===r\|\|null===(o=r.groupsetting)\|\|void 0===o\|\|null===(i=o.customset)\|\|void 0===i?void 0:i.groups))for(const n of e.q.groupsetting.customset.groups){if(!Array.isArray(n.values))throw"group.values[] not array from tw.q.groupsetting.customset.groups";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}if("predefined-groupset"==(null===(s=e.q)\|\|void 0===s?void 0:s.type)&&Number.isInteger(null===(a=e.q.groupsetting)\|\|void 0===a?void 0:a.predefined_groupset_idx)&&null!==(l=e.term.groupsetting)&&void 0!==l&&l.lst[e.q.groupsetting.predefined_groupset_idx])for(const n of e.term.groupsetting.lst[e.q.groupsetting.predefined_groupset_idx]){if(!Array.isArray(n.values))throw"group.values[] not array from tw.term.groupsetting.lst[]";if(-1!=n.values.findIndex((e=>e.key==t)))return n.name}}(t[n.term.id],n);e&&(t[n.term.id]=e)}}function M(t,e){for(const n of t)if(n.startunbounded){if(e<n.stop)return n.label;if(n.stopinclusive&&e==n.stop)return n.label}else if(n.stopunbounded){if(e>n.start)return n.label;if(n.startinclusive&&e==n.start)return n.label}else if((e>n.start\|\|e===n.start&&n.startinclusive)&&(e<n.stop\|\|e===n.stop&&n.stopinclusive))return n.label}function T(t){for(const n of t)if(null==n.id\|\|""==n.id){var e;if(null==n\|\|null===(e=n.term)\|\|void 0===e\|\|!e.id)throw"tw.id and tw.term are both missing";n.id=n.term.id}else n.term\|\|(n.term={id:n.id})}async function C(t,e,n,r){if(T(e),r){if(!Array.isArray(r))throw"geneTwLst not array";t.isoforms=[];for(const e of r){var i;if(null==e\|\|null===(i=e.term)\|\|void 0===i\|\|!i.name)throw"gene tw missing .term.name";if(e.term.isoform)t.isoforms.push(e.term.isoform);else{var a,u;if("object"!=typeof t.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(null===(a=t.genome)\|\|void 0===a\|\|null===(u=a.genedb)\|\|void 0===u\|\|!u.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const n=t.genome.genedb.get_gene2canonicalisoform.get(e.term.name);if(null==n\|\|!n.isoform)continue;t.isoforms.push(n.isoform)}}}"samples"==t.get&&((t.ssm_id_lst\|\|t.isoform)&&(e.some((t=>"ssm.ssm_id"==t.id))\|\|e.push({term:{id:"ssm.ssm_id"}}),e.some((t=>"case.observation.read_depth.t_alt_count"==t.id))\|\|e.push({term:{id:"case.observation.read_depth.t_alt_count"}}),e.some((t=>"case.observation.read_depth.t_depth"==t.id))\|\|e.push({term:{id:"case.observation.read_depth.t_depth"}}),e.some((t=>"case.observation.read_depth.n_depth"==t.id))\|\|e.push({term:{id:"case.observation.read_depth.n_depth"}}),e.some((t=>"case.observation.sample.tumor_sample_uuid"==t.id))\|\|e.push({term:{id:"case.observation.sample.tumor_sample_uuid"}})),e.some((t=>"case.case_id"==t.id))\|\|e.push({term:{id:"case.case_id"}}),e.some((t=>"case.submitter_id"==t.id))\|\|e.push({term:{id:"case.submitter_id"}})),"summary"!=t.get&&"sunburst"!=t.get\|\|e.some((t=>"case.submitter_id"==t.id))\|\|e.push({term:{id:"case.submitter_id"}});const d=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&d.push({term:e,q:t.q})}const h=e.map((t=>t.term.id));t.hiddenmclass&&(h.push("ssm.consequence.transcript.consequence_type"),h.push("ssm.consequence.transcript.transcript_id")),t.rglst&&(h.push("ssm.chromosome"),h.push("ssm.start_position"));const p={size:1e4,fields:h.join(",")};_(t,n),p.filters=Z.filters(t,n);const m=S(t),g=await s().post(l().join(f,Z.endpoint),{headers:m,body:JSON.stringify(p)});let y;delete t.isoforms;try{y=JSON.parse(g.body)}catch(t){throw"invalid JSON from GDC for variant2samples query"}if(!y.data\|\|!y.data.hits)throw"variant2samples data structure not data.hits[]";if(!Array.isArray(y.data.hits))throw"variant2samples re.data.hits is not array for query";const v=[];for(const e of y.data.hits){if(!e.case)throw"variant2samples .case{} missing from a hit";const r={};if(e.ssm&&(r.ssm_id=e.ssm.ssm_id),t.hiddenmclass){var b;if(!Array.isArray(null===(b=e.ssm)\|\|void 0===b?void 0:b.consequence))continue;const n={};if(x(n,e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform))),t.hiddenmclass.has(n.class))continue}if(t.rglst){var w,k;if(null===(w=e.ssm)\|\|void 0===w\|\|!w.chromosome\|\|null===(k=e.ssm)\|\|void 0===k\|\|!k.start_position)continue;if(!t.rglst.find((t=>t.chr==e.ssm.chromosome&&t.start<e.ssm.start_position&&t.stop>=e.ssm.start_position)))continue}var q,N,C,R;if(t.variant2samples?r.sample_id=await j(e.case,n,!1):(r.sample_id=e.case.case_id,r.__sampleName=e.case.submitter_id),e.case.case_id)r.sample_URLid=e.case.case_id,null!==(q=e.case)&&void 0!==q&&null!==(N=q.observation)&&void 0!==N&&null!==(C=N[0])&&void 0!==C&&null!==(R=C.sample)&&void 0!==R&&R.tumor_sample_uuid&&(r.sample_URLid=r.sample_URLid+"?bioId="+e.case.observation[0].sample.tumor_sample_uuid);for(const t of d)A(r,e.case,t);O(e.case,r),E(r,n),v.push(r)}if(function(t,e){for(const r of e){var n;if(("integer"==r.term.type\|\|"float"==r.term.type)&&null!==(n=r.q)&&void 0!==n&&n.mode)if("discrete"==r.q.mode\|\|"binary"==r.q.mode){const e={};for(const n of t){const t=n[r.term.id];Number.isFinite(t)&&("min"in e?(e.min=Math.min(t,e.min),e.max=Math.max(t,e.max)):(e.min=t,e.max=t))}const n=(0,o.compute_bins)(r.q,(t=>e));for(const e of t){const t=e[r.term.id];Number.isFinite(t)&&(e[r.term.id]=M(n,t))}}else if("continuous"!=r.q.mode)throw"mayApplyBinning: unknown numeric q.mode"}}(v,d),r){const t={gene:r.map((t=>t.term.name)).join(","),twLst:d},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)v.push(e)}const I=new Map;for(const t of v)(0,c.z9)([t],I,t.ssm_id);return[...I.values()]}async function j(t,e,n){var r,o,i;return n&&t.case_id?t.case_id:null!=t&&null!==(r=t.observation)&&void 0!==r&&null!==(o=r[0])&&void 0!==o&&null!==(i=o.sample)&&void 0!==i&&i.tumor_sample_uuid?await e.aliquot2submitter.get(t.observation[0].sample.tumor_sample_uuid):t.case_id\|\|t.submitter_id}function O(t,e){if(!t.observation)return;const n=t.observation[0];n&&n.read_depth&&(e.formatK2v={TumorAC:n.read_depth.t_depth-n.read_depth.t_alt_count+","+n.read_depth.t_alt_count,NormalDepth:n.read_depth.n_depth})}function E(t,e){var n;const r=t["case.project.project_id"];r&&(t.caseIsOpenAccess=null===(n=e.gdcOpenProjects)\|\|void 0===n?void 0:n.has(r))}async function R(t,e,n,r){T(t);const o=[];for(const e of t)e.term&&"categorical"==e.term.type&&o.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const i=function(t){const e=[];for(const n of t)if(n.id)if(n.type="categorical")e.push(n.path+" {buckets { doc_count, key }}");else{if("integer"!=n.type&&"float"!=n.type)throw"unknown term type";e.push(n.path+" {stats { count }}")}const n=`query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\t${e.join("\n")}\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t}`;return n}(o),a=function(t,e){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};if(t&&t.tid2value)for(const r in t.tid2value){e.cohort.termdb.q.termjsonByOneid(r)&&n.filters.content.push({op:"in",content:{field:r.replace(/^case\./,"cases."),value:[t.tid2value[r]]}})}t&&t.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:t.ssm_id_lst.split(",")}});t.filterObj&&n.filters.content.push((0,u.P)(t.filterObj));return n}(e,r),l=await s().post(d,{headers:S(e),body:JSON.stringify({query:i,variables:a})});let c;try{c=JSON.parse(l.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+i+" and filter: "+filter}const f=["data","explore","cases","aggregations"];let h=c[f[0]];for(let t=1;t<f.length;t++)if(h=h[f[t]],!h)throw`.${f[t]} missing from data structure of termid2totalsize2 for query :${i} and filter: ${filter}`;for(const t of o){if("categorical"==t.type&&!Array.isArray(h[t.path].buckets))throw f.join(".")+" not array for query :"+i+" and filter: "+filter;if(("integer"==t.type\|\|"float"==t.type)&&"object"!=typeof h[t.path].stats)throw f.join(".")+" not object for query :"+i+" and filter: "+filter}const p=new Map;for(const t of o)if("categorical"==t.type){const e=h[t.path].buckets,n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);p.set(t.id,n)}else if("integer"==t.type\|\|"float"==t.type){const e=h[t.path].stats.count;p.set(t.id,{total:e})}return n?[p,n]:p}function I(t){const e=["consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change"];t.queries.snvindel.m2csq.get=async t=>{const n=await s()(f+"/ssms/"+t.ssm_id+"?fields="+e.join(","),{method:"GET",headers:S(t)});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid json in response"}if(!r.data\|\|!r.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(r.data.consequence))throw".data.consequence not array";return r.data.consequence.map((t=>t.transcript))}}function P(t,e){t.queries.singleSampleMutation.get=async(n,r)=>{if(!n)throw"sampleName missing";return r.case_id=t.map2caseid.get(n),r.case_id\|\|(r.case_id=await async function(t){const e=await s().post("https://api.gdc.cancer.gov/cases",{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:1,fields:"case_id,submitter_id",filters:{op:"or",content:[{op:"=",content:{field:"samples.portions.analytes.aliquots.aliquot_id",value:[t]}},{op:"=",content:{field:"submitter_id",value:[t]}},{op:"=",content:{field:"samples.submitter_id",value:[t]}}]}})}),n=JSON.parse(e.body);for(const t of n.data.hits)if(t.case_id)return t.case_id;throw"cannot convert to case_id (uuid)"}(n)),await L(r,t,e)}}function F(t){return async(e,n)=>{try{const r=t[e.query.genome];if(!r)throw"invalid genome";const o=r.datasets[e.query.dslabel];if(!o)throw"invalid dslabel";if(!e.query.case_id)throw".case_id missing";n.send({mlst:await L(e.query,o,r)})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message\|\|t})}}}async function L(t,e,n){const o=[];{const e=await s().post(l().join(f,$.endpoint),{headers:S(t),body:JSON.stringify({size:1e3,fields:$.fields.join(","),filters:$.filters(t)})}),i=JSON.parse(e.body);for(const t of i.data.hits){let e;for(const n of t.consequence)if(n.transcript&&n.transcript.gene&&n.transcript.gene.symbol){e=n.transcript.gene.symbol;break}if(!e)continue;const i=n.genedb.get_gene2canonicalisoform.get(e);if(null==i\|\|!i.isoform)continue;let s=t.consequence.find((t=>t.transcript.transcript_id==i.isoform));s\|\|(s=t.consequence[0]);const a=s.transcript.aa_change\|\|s.transcript.consequence_type,[l,c,u]=r.vepinfo(s.transcript.consequence_type);o.push({dt:r.dtsnvindel,mname:a,class:c,gene:s.transcript.gene.symbol,chr:t.chromosome,pos:t.start_position,ref:t.reference_allele,alt:t.tumor_allele})}}{const e=await async function(t){const e=S(t),n=await s().post(l().join(f,"files"),{headers:e,body:JSON.stringify({size:1e4,fields:["cases.samples.sample_type","data_type","file_id","data_format","experimental_strategy","analysis.workflow_type"].join(","),filters:function(t){if(!t.case_id)throw".case_id missing";return{op:"and",content:[{op:"in",content:{field:"cases.case_id",value:[t.case_id]}},{op:"in",content:{field:"data_type",value:["Masked Copy Number Segment","Copy Number Segment","Transcript Fusion"]}}]}}(t)})}),o=JSON.parse(n.body);if(!Array.isArray(o.data.hits))throw"re.data.hits[] not array";let i,a,c;for(const t of o.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){var u,d,h;const e=null===(u=t.cases)\|\|void 0===u\|\|null===(d=u[0].samples)\|\|void 0===d\|\|null===(h=d[0])\|\|void 0===h?void 0:h.sample_type;if(!e)continue;if(e.includes("Normal"))continue;if("Masked Copy Number Segment"!=t.data_type)continue;i=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;a=t.file_id;continue}}}else{var p;if("RNA-Seq"!=t.experimental_strategy)continue;if("Arriba"!=(null===(p=t.analysis)\|\|void 0===p?void 0:p.workflow_type))continue;if("Transcript Fusion"!=t.data_type)continue;c=t.file_id}const m=[];if(a){const t=(await s()(l().join(f,"data")+"/"+a,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(7!=n.length)continue;const o=Number(n[4]),i=Number(n[5]),s=Number(n[6]);if(Number.isNaN(o)\|\|Number.isNaN(i)\|\|Number.isNaN(s))continue;const a={dt:r.dtcnv,chr:n[1],start:Number(n[2]),stop:Number(n[3]),value:o};!a.chr\|\|Number.isNaN(a.start)\|\|Number.isNaN(a.stop)\|\|(m.push(a),o>0&&0==s&&i>0&&m.push({dt:r.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(i){const t=(await s()(l().join(f,"data")+"/"+i,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(6!=n.length)continue;if(!n[1])continue;const o={dt:r.dtcnv,chr:"chr"+n[1],start:Number(n[2]),stop:Number(n[3]),value:Number(n[5])};Number.isNaN(o.start)\|\|Number.isNaN(o.stop)\|\|Number.isNaN(o.value)\|\|m.push(o)}}if(c)try{const t=(await s()(l().join(f,"data")+"/"+c,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t"),o={dt:r.dtfusionrna,chrA:n[0],posA:Number(n[1]),chrB:n[3],posB:Number(n[4])};o.chrA&&o.chrB&&!Number.isNaN(o.posA)&&!Number.isNaN(o.posB)&&(N(o,n[6]),m.push(o))}}catch(t){}return m}(t);o.push(...e)}return o}function D(t){return async(e,n)=>{try{if(!t[e.query.genome])throw"invalid genome";n.send({genes:await z({filter:e.query.filter0,CGConly:parseInt(e.query.CGConly),maxGenes:e.query.maxGenes})})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message\|\|t})}}}async function z({filter:t,CGConly:e,maxGenes:n}){let r={op:"and",content:[]};if(t){if("object"!=typeof t)throw"filter not object";r=t}const o=await s().post(l().join(f,"/analysis/top_mutated_genes_by_project"),{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:n\|\|50,fields:"symbol",filters:B(r,e)})}),i=JSON.parse(o.body),a=[];for(const t of i.data.hits)t.symbol&&a.push(t.symbol);return a}function B(t,e){let n;if("in"==t.op)n={op:"and",content:[t]};else{if("and"!=t.op)throw'f.op not "in" or "and"';n=t}return n.content.push({op:"NOT",content:{field:"ssms.consequence.transcript.annotation.vep_impact",value:"missing"}}),n.content.push({op:"in",content:{field:"ssms.consequence.transcript.consequence_type",value:["missense_variant","frameshift_variant","start_lost","stop_lost","stop_gained"]}}),e&&n.content.push({op:"in",content:{field:"genes.is_cancer_gene_census",value:["true"]}}),n}const $={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"],filters:t=>{const e={op:"and",content:[]};if(t.isoform){if("string"!=typeof t.isoform)throw".isoform value not string";e.content.push({op:"=",content:{field:"consequence.transcript.transcript_id",value:[t.isoform]}})}if(t.case_id){if("string"!=typeof t.case_id)throw".case_id value not string";e.content.push({op:"=",content:{field:"cases.case_id",value:[t.case_id]}})}if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";e.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push((0,u.P)(t.filterObj)),e}},Z={endpoint:"/ssm_occurrences",size:1e5,fields:["ssm.ssm_id","case.case_id","case.submitter_id","case.observation.sample.tumor_sample_uuid"],filters:(t,e)=>{const n={op:"and",content:[]};if(t.ssm_id_lst){if("string"!=typeof t.ssm_id_lst)throw"ssm_id_lst not string";n.content.push({op:"=",content:{field:"ssm.ssm_id",value:t.ssm_id_lst.split(",")}})}else if(t.isoform)n.content.push({op:"=",content:{field:"ssms.consequence.transcript.transcript_id",value:[t.isoform]}});else{if(!t.isoforms)throw".ssm_id_lst, .isoform, .isoforms are all missing";if(!Array.isArray(t.isoforms))throw".isoforms[] not array";n.content.push({op:"in",content:{field:"ssms.consequence.transcript.transcript_id",value:t.isoforms}})}if(t.rglst&&(n.content.push({op:">=",content:{field:"ssms.start_position",value:t.rglst[0].start}}),n.content.push({op:"<=",content:{field:"ssms.start_position",value:t.rglst[0].stop}})),t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";n.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}if(t.filter0&&n.content.push(t.filter0),t.filterObj&&n.content.push((0,u.P)(t.filterObj)),t.tid2value)for(const r in t.tid2value){const o=e.cohort.termdb.q.termjsonByOneid(r);if(o)if("categorical"==o.type)n.content.push({op:"in",content:{field:r,value:[t.tid2value[r]]}});else if("integer"==o.type)for(const e of t.tid2value[r])n.content.push({op:e.op,content:{field:r,value:e.range}})}return n}}},9191:(t,e,n)=>{"use strict";n.r(e),n.d(e,{client_copy:()=>J,cnvByRangeGetter_file:()=>lt,init:()=>W,snvindelByRangeGetter_bcf:()=>K,ssmIdFieldsSeparator:()=>Z,svfusionByRangeGetter_file:()=>at,validate_termdb:()=>H});var r=n(7147),o=n.n(r),i=n(4521),s=n.n(i),a=n(1017),l=n.n(a),c=n(9064),u=n(6718),f=n(5243),d=n(6452),h=n.n(d),p=n(1575),m=n(334),g=n.n(m);const y=process.env.PP_GDC_HOST\|\|"https://api.gdc.cancer.gov",v=y+(y.includes("/v0")?"":"/v0")+"/graphql",b=l().join(y,"ssm_occurrences/_mapping"),_={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}}},w=function(){const t={"case.demographic.age_at_index":{bin_size:10,first_bin_stop:30},"case.demographic.days_to_birth":{bin_size:1e3,first_bin_stop:-3e3},"case.diagnoses.circumferential_resection_margin":null,"case.demographic.days_to_death":{bin_size:1e3,first_bin_stop:1e3},"case.demographic.year_of_birth":{bin_size:10,first_bin_stop:1930},"case.demographic.year_of_death":{bin_size:5,first_bin_stop:1995},"case.diagnoses.age_at_diagnosis":{bin_size:3e3,first_bin_stop:1e4},"case.diagnoses.days_to_diagnosis":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.days_to_hiv_diagnosis":null,"case.diagnoses.days_to_last_follow_up":{bin_size:1e3,first_bin_stop:1500},"case.diagnoses.days_to_last_known_disease_status":{bin_size:500,first_bin_stop:1500},"case.diagnoses.days_to_new_event":null,"case.diagnoses.days_to_recurrence":{bin_size:100,first_bin_stop:200},"case.diagnoses.ldh_level_at_diagnosis":null,"case.diagnoses.ldh_normal_range_upper":null,"case.diagnoses.lymph_nodes_positive":null,"case.diagnoses.lymph_nodes_tested":null,"case.diagnoses.pathology_details.breslow_thickness":null,"case.diagnoses.pathology_details.circumferential_resection_margin":null,"case.diagnoses.pathology_details.greatest_tumor_dimension":null,"case.diagnoses.pathology_details.gross_tumor_weight":null,"case.diagnoses.pathology_details.lymph_nodes_positive":{bin_size:10,first_bin_stop:10},"case.diagnoses.pathology_details.lymph_nodes_tested":{bin_size:10,first_bin_stop:25},"case.diagnoses.pathology_details.number_proliferating_cells":null,"case.diagnoses.pathology_details.percent_tumor_invasion":null,"case.diagnoses.pathology_details.peripancreatic_lymph_nodes_tested":{bin_size:10,first_bin_stop:35},"case.diagnoses.pathology_details.prostatic_chips_positive_count":null,"case.diagnoses.pathology_details.prostatic_chips_total_count":null,"case.diagnoses.pathology_details.prostatic_involvement_percent":null,"case.diagnoses.pathology_details.tumor_largest_dimension_diameter":{bin_size:10,first_bin_stop:20},"case.diagnoses.peripancreatic_lymph_nodes_tested":null,"case.diagnoses.treatments.days_to_treatment_end":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.treatments.days_to_treatment_start":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.treatments.number_of_cycles":null,"case.diagnoses.treatments.treatment_dose":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.tumor_largest_dimension_diameter":null,"case.diagnoses.year_of_diagnosis":{bin_size:10,first_bin_stop:1995},"case.exposures.alcohol_days_per_week":{bin_size:1,first_bin_stop:2},"case.exposures.bmi":null,"case.exposures.cigarettes_per_day":{bin_size:50,first_bin_stop:20},"case.exposures.height":null,"case.exposures.pack_years_smoked":{bin_size:50,first_bin_stop:40},"case.exposures.tobacco_smoking_onset_year":{bin_size:100,first_bin_stop:1998},"case.exposures.tobacco_smoking_quit_year":{bin_size:100,first_bin_stop:2e3},"case.exposures.weight":null,"case.exposures.years_smoked":{bin_size:10,first_bin_stop:30},"case.family_histories.relationship_age_at_diagnosis":null},e={};for(const n in t){const r=t[n];e[n]=r?{default:{mode:"discrete",type:"regular-bin",bin_size:r.bin_size,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:r.first_bin_stop}}}:_}return e}(),x="ssm_occurrence_centrics";async function k(t){const e=new Map,n=await h()(b,{method:"GET",headers:{"Content-Type":"application/json",Accept:"application/json"}});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid JSON from GDC dictionary"}if(!r._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(r.fields))throw".fields not array";if(!Array.isArray(r.nested))throw".nested not array";const o=new Set(r.nested);let i=0,s=0,a=0,c=0,u=0,f=0;for(const t of r.fields){if(A(t)){i++;continue}const n=t.split(".");for(let t=1;t<n.length;t++){const i=n.slice(0,t).join("."),l=i+"."+n[t],f=n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),d={id:l.toLowerCase(),name:f,included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){d.isleaf=!0;const t=r._mapping[x+"."+l];t&&("keyword"==t.type?(d.type="categorical",a++):"long"==t.type?(d.type="integer",d.bins=w[d.id]\|\|JSON.parse(JSON.stringify(_)),c++):"double"==t.type?(d.type="float",d.bins=w[d.id]\|\|JSON.parse(JSON.stringify(_)),u++):console.log("GDC !!! ERR !!! Unknown variable type: "+t.type),"integer"!=d.type&&"float"!=d.type\|\|w[d.id]\|\|(console.log(`GDC !!! Lack bin config for ${d.type} ${d.id}`),await N(d.id))),d.type\|\|s++,q(d)}if(1==t);else if(d.parent_id=i,d.type){d.included_types_set.add(d.type);let t=e.get(i);for(;t&&(t.included_types_set.add(d.type),t.child_types_set.add(d.type),t.parent_id);)t=e.get(t.parent_id)}o.has(l)&&(d.isObjectList=!0),e.set(l,d)}}for(const t of e.values())t.type\|\|f++,t.included_types=[...t.included_types_set],t.child_types=[...t.child_types_set],delete t.included_types_set,delete t.child_types_set;console.log("GDC dictionary:",e.size,"total variables,",i,"lines skipped,",s,"lines with unknown term type,","categorical="+a,"integer="+c,"float="+u,"parent="+f),Object.freeze(e),function(t,e){const n=t.cohort.termdb.q={};async function r(e,n){if(0==e.length\|\|!n)return;const r=await t.termdb.termid2totalsize2.get(e.map((t=>t.id)),JSON.parse(n));for(const t of e)if(t){const e=r.get(t.id);"categorical"==t.type&&e?e.length?t.samplecount=e.map((t=>t[1])).reduce(((t,e)=>t+e)):(t.disabled=!0,t.samplecount=0):"integer"!=t.type&&"float"!=t.type\|\|(t.samplecount=e.total,0==e.total&&(t.disabled=!0))}}n.getRootTerms=async(t,n=null)=>{const o=[];for(const t of e.values())null==t.parent_id&&o.push(JSON.parse(JSON.stringify(t)));return await r(o,n),o},n.getTermChildren=async(t,n=null,o=null)=>{const i=[];for(const n of e.values())n.parent_id==t&&i.push(JSON.parse(JSON.stringify(n)));return await r(i,o),i},n.findTermByName=async(t,n=null,o,i=null,s=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const a=[];for(const n of e.values())s&&!(0,p.CG)(n,s)\|\|n.id.includes(t)&&a.push(JSON.parse(JSON.stringify(n)));return await r(a,i),a},n.getAncestorIDs=t=>{if(!e.has(t))return;const n=t.split("."),r=[];for(let t=1;t<n.length;t++)r.push(n.slice(0,t+1).join("."));return r},n.getAncestorNames=n.getAncestorIDs,n.termjsonByOneid=t=>{const n=e.get(t);return n?JSON.parse(JSON.stringify(n)):null},n.getSupportedChartTypes=()=>{const t={},n={};for(const r of e.values())r.type&&(r.cohort in t\|\|(t[r.cohort]=["barchart","table","regression"],n[r.cohort]=0),"survival"!=r.type\|\|t[r.cohort].includes("survival")\|\|t[r.cohort].push("survival"),"condition"!=r.type\|\|t[r.cohort].includes("cuminc")\|\|t[r.cohort].push("cuminc"),"float"!=r.type&&"integer"!=r.type\|\|(n[r.cohort]+=r.samplecount));for(const e in n)n[e]>0&&t[e].push("boxplot"),n[e]>1&&t[e].push("scatterplot");return t}}(t,e),t.cohort.termdb.termtypeByCohort=[],a&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),c&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),u&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),await async function(t){var e,n,r;const o={"Content-Type":"application/json",Accept:"application/json"},i={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},s=await h()(l().join(y,"files"),{method:"POST",headers:o,body:JSON.stringify(i)}),a=JSON.parse(s.body);if(t.gdcOpenProjects=new Set,null!=a&&null!==(e=a.data)&&void 0!==e&&null!==(n=e.aggregations)&&void 0!==n&&null!==(r=n["cases.project.project_id"])&&void 0!==r&&r.buckets){for(const e of a.data.aggregations["cases.project.project_id"].buckets)e.key&&t.gdcOpenProjects.add(e.key);console.log("GDC open-access projects:",t.gdcOpenProjects.size)}else console.log("getting open project_id but return is not re.data.aggregations['cases.project.project_id'].buckets")}(t),async function(){try{await M(y+"/ssms"),await M(y+"/ssm_occurrences"),await M(y+"/cases"),await M(y+"/files"),await M(y+"/analysis/top_mutated_genes_by_project"),await async function(t){const e=new Date;try{const e="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}}";await h().post(t,{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({query:e,variables:{}})})}catch(e){throw"gdc api down: "+t}console.log("GDC GraphQL API okay: "+t,new Date-e,"ms")}(v)}catch(t){console.error(`\n##########################################\n#\n# GDC API unavailable\n# ${y}\n# ${v}\n#\n##########################################`)}}(),async function(t){t.aliquot2submitter={cache:new Map,get:async e=>t.aliquot2submitter.cache.has(e)?t.aliquot2submitter.cache.get(e):e},t.map2caseid={cache:new Map,get:e=>t.map2caseid.cache.get(e)};try{if(g().features.stopGdcCacheAliquot)return console.log("GDC aliquot2submitter not cached!");const e=await T(t,1,0);if(!Number.isInteger(e))throw"gdc totalCases not integer";const n=new Date;console.log("GDC: Start to cache sample IDs of",e,"cases...");const r=1e3;for(let n=0;n<Math.ceil(e/r);n++)await T(t,r,1e3n);console.log("GDC: Done caching sample IDs",Math.ceil((new Date-n)/1e3),"s"),console.log("\t",t.aliquot2submitter.cache.size,"aliquot IDs to sample submitter id"),console.log("\t",t.map2caseid.cache.size,"different ids to case uuid.")}catch(t){console.log("Error at caching: "+t)}}(t)}function q(t){"case.diagnoses.age_at_diagnosis"!=t.id\|\|(t.printDays2years=!0)}async function N(t){const e=t.replace("case.","").replace(".","__"),n=`\n\t query ContinuousAggregationQuery($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 ${e} {\n\t\t\t stats {\n\t\t\t\t\tMin : min\n\t\t\t\t\tMax: max\n\t\t\t\t\tMean: avg\n\t\t\t\t\tSD: std_deviation\n\t\t\t\t\tcount\n\t\t\t\t}\n\t\t\t\trange(ranges: $filters2) {\n\t\t\t\t buckets {\n\t\t\t\t\tdoc_count\n\t\t\t\t\tkey\n\t\t\t\t }\n\t\t\t\t}\n\t\t\t }\n\t\t\t}\n\t\t }\n\t\t}\n\t }\n\t}`,r={caseFilters:{},filters:{},filters2:{op:"range",content:[{ranges:[{from:0,to:1}]}]}};try{const o=await h().post(v,{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({query:n,variables:r})}),i=JSON.parse(o.body).data.viewer.explore.cases.aggregations[e].stats;console.log(`${t} Min=${i.Min} Max=${i.Max} Mean=${i.Mean} Median=${i.Median} SD=${i.SD} Count=${i.count}`)}catch(e){console.log(`${t} ??? ERR ???`)}}const S=new Set(["case.consent_type","case.days_to_consent","case.days_to_index"]);function A(t){return!!(t.startsWith("ssm")\|\|t.startsWith("case.observation")\|\|t.startsWith("case.available_variation_data"))\|\|(!(!t.endsWith("_id")\|\|t.endsWith("project_id"))\|\|(!!S.has(t)\|\|void 0))}async function M(t){try{const e=new Date;await h()(t),console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){throw"gdc api down: "+t}}async function T(t,e,n,r){var o,i,s;const a=["fields=submitter_id,samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(r)a.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+r+'"]}}]}');else{if(!Number.isInteger(e)\|\|!Number.isInteger(n))throw"size and from not integers";a.push("size="+e),a.push("from="+n)}const l=await h()(y+"/cases?"+a.join("&")),c=JSON.parse(l.body);if(!Array.isArray(null==c\|\|null===(o=c.data)\|\|void 0===o?void 0:o.hits))throw"re.data.hits[] not array";for(const e of c.data.hits){const n=e.id;if(!n)throw"h.id (case uuid) missing";const r=e.submitter_id;if(!r)throw"h.submitter_id missing";if(t.map2caseid.cache.set(r,n),Array.isArray(e.samples))for(const r of e.samples){const e=r.submitter_id;if(!e)throw"sample.submitter_id missing";if(t.map2caseid.cache.set(e,n),Array.isArray(r.portions))for(const o of r.portions)if(Array.isArray(o.analytes))for(const r of o.analytes)if(Array.isArray(r.aliquots))for(const o of r.aliquots){const r=o.aliquot_id;if(!r)throw"aliquot.aliquot_id missing";t.aliquot2submitter.cache.set(r,e),t.map2caseid.cache.set(r,n)}}}return null===(i=c.data)\|\|void 0===i\|\|null===(s=i.pagination)\|\|void 0===s?void 0:s.total}var C=n(817),j=n(3856),O=n(3625),E=n(7027),R=n(478),I=n(2273),P=n(2852),F=n(394),L=n(1711),D=n(1883),z=n(2188),B=n(2974),$=n(3795);const Z=".",G="Ancestry_PC_",U="Unannotated";async function W(t,e,n,r=null,i=null){var s,a;await H(t),t.queries&&(await async function(t,e){const n=t.queries.snvindel;if(!n)return;if(n.url){if(!n.url.base)throw".snvindel.url.base missing";if(!n.url.key)throw".snvindel.url.key missing"}if(!n.byisoform&&!n.byrange)throw"byisoform and byrange are both missing on queries.snvindel";if(n.byrange)if(n.byrange.gdcapi)f.validate_query_snvindel_byrange(t);else if(n.byrange.bcffile){var r;n.byrange.bcffile=n.byrange.bcffile.startsWith(g().tpmasterdir)?n.byrange.bcffile:l().join(g().tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await K(t,e),null!==(r=n.byrange._tk)&&void 0!==r&&r.samples.length\|\|delete n.byrange._tk.samples,Q(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}else{if(!n.byrange.chr2bcffile)throw"unknown query method for queries.snvindel.byrange";n.byrange._tk={chr2files:{}};for(const t in n.byrange.chr2bcffile)n.byrange._tk.chr2files[t]={file:l().join(g().tpmasterdir,n.byrange.chr2bcffile[t])};delete n.byrange.chr2bcffile,n.byrange.get=await K(t,e),n.byrange._tk.samples.length\|\|delete n.byrange._tk.samples,Q(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";f.validate_query_snvindel_byisoform(t)}if(n.m2csq){if(!n.m2csq.by)throw".by missing from queries.snvindel.m2csq";if("ssm_id"!=n.m2csq.by)throw"unknown value of queries.snvindel.m2csq.by";if(!n.m2csq.gdcapi)throw"unknown query method for queries.snvindel.m2csq";f.validate_m2csq(t)}}(t,e),await async function(t,e){const n=t.queries.svfusion;if(!n)return;if(!n.byrange)throw"byrange missing from queries.svfusion";if(n.byrange){if(!n.byrange.file)throw"unknown query method for svfusion.byrange";n.byrange.file=n.byrange.file.startsWith(g().tpmasterdir)?n.byrange.file:l().join(g().tpmasterdir,n.byrange.file),n.byrange.get=await at(t,e),Q(t,n.byrange.samples,"svfusion.byrange")}}(t,e),await async function(t,e){const n=t.queries.geneCnv;if(!n)return;if(!n.bygene)throw"geneCnv.bygene missing";n.bygene.gdcapi&&f.validate_query_geneCnv2(t)}(t),await async function(t,e){const n=t.queries.cnv;if(!n)return;if(!n.byrange)throw"byrange missing from queries.cnv";if(n.byrange){if(!n.byrange.file)throw"unknown query method for cnv.byrange";n.byrange.file=n.byrange.file.startsWith(g().tpmasterdir)?n.byrange.file:l().join(g().tpmasterdir,n.byrange.file),n.byrange.get=await lt(t,e),Q(t,n.byrange.samples,"cnv.byrange")}}(t,e),await async function(t,e){const n=t.queries.ld;if(!n)return;if(!Array.isArray(n.tracks)\|\|!n.tracks.length)throw"ld.tracks[] not nonempty array";for(const t of n.tracks){if(!t.name)throw"name missing from one of ld.tracks[]";if(!t.file)throw".file missing from one of ld.tracks[]";t.file0=t.file,t.file=l().join(g().tpmasterdir,t.file),await j.validate_tabixfile(t.file),t.nochr=await j.tabix_is_nochr(t.file,null,e)}if(!n.overlay)throw"ld.overlay{} missing";if(!n.overlay.color_0)throw"ld.overlay.color_0 missing";if(!n.overlay.color_1)throw"ld.overlay.color_1 missing"}(t,e),await async function(t,e){const n=t.queries.geneExpression;if(!n)return;if(n.gdcapi)return void f.validate_query_geneExpression(t);if(!n.file)throw".file missing from queries.geneExpression";n.file=l().join(g().tpmasterdir,n.file),await j.validate_tabixfile(n.file),n.nochr=await j.tabix_is_nochr(n.file,null,e),n.get=async e=>{const r=await nt(e,null,t);if(0==(null==r?void 0:r.size))return new Map;const o=new Map;for(const t of e.genes)o.set(t.gene,{}),await j.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:e=>{const n=e.split("\t");let i;try{i=JSON.parse(n[3])}catch(t){return}i.gene==t.gene&&(r&&!r.has(i.sample)\|\|(o.get(t.gene)[i.sample]=i.value))}});return o}}(t,e),await async function(t,e){const n=t.queries.singleSampleMutation;if(!n)return;if(n.gdcapi)f.validate_query_singleSampleMutation(t,e);else{if(!n.folder)throw"unknown query method for singleSampleMutation";n.get=async e=>{var r,o,i;let s=e;if(null!==(r=t.cohort)&&void 0!==r&&null!==(o=r.termdb)&&void 0!==o&&null!==(i=o.q)&&void 0!==i&&i.sampleName2id&&(s=t.cohort.termdb.q.sampleName2id(e),null==s))return[];const a=await j.read_file(l().join(g().tpmasterdir,n.folder,s.toString()));return JSON.parse(a)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGenomeQuantification;if(!n)return;for(const r in n){if(!Number.isFinite(n[r].min))throw"min not a number";if(!Number.isFinite(n[r].max))throw"max not a number";if(n[r].min>=n[r].max)throw"min>=max";if(!n[r].folder)throw"unknown query method for singleSampleGenomeQuantification";n[r].get=async(o,i)=>{var s,a,c;let u=o;if(null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.termdb)&&void 0!==a&&null!==(c=a.q)&&void 0!==c&&c.sampleName2id&&(u=t.cohort.termdb.q.sampleName2id(o),null==u))return[];return await st(l().join(g().tpmasterdir,n[r].folder,u.toString()),e,n[r],i)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGbtk;if(!n)return;for(const e in n){if(!Number.isFinite(n[e].min))throw"min not a number";if(!Number.isFinite(n[e].max))throw"max not a number";if(n[e].min>=n[e].max)throw"min>=max";if(!n[e].folder)throw"unknown query method for singleSampleGbtk";n[e].get=async r=>{var i,s,a;let c=r;if(null!==(i=t.cohort)&&void 0!==i&&null!==(s=i.termdb)&&void 0!==s&&null!==(a=s.q)&&void 0!==a&&a.sampleName2id&&(c=t.cohort.termdb.q.sampleName2id(r),null==c))return{};const u=l().join(n[e].folder,c+".gz");try{return await o().promises.stat(l().join(g().tpmasterdir,u)),{path:u}}catch(t){return{}}}}}(t),await async function(t,e){const n=t.queries.probe2cnv;if(!n)return;if(n.file)n.file=l().join(g().tpmasterdir,n.file),await j.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on probe2cnv";n.dir=await j.cache_index(n.url,n.indexURL)}n.nochr=await j.tabix_is_nochr(n.file\|\|n.url,null,e);{const e=await j.get_header_tabix(n.file);if(!e[0])throw"header line missing from "+n.file;const r=e[0].split("\t");if(r.length<3)throw"probe2cnv header line less than 3 fields";n.samples=r.slice(2).map((e=>({name:t.cohort.termdb.q.sampleName2id(e)})))}n.get=async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";if(e.cnvGainCutoff&&!Number.isFinite(e.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(e.cnvLossCutoff&&!Number.isFinite(e.cnvLossCutoff))throw"cnvLossCutoff is not finite";const r=[];{const o=await nt(e,n.samples,t);if(o){if(0==o.size)return[];for(const[t,e]of n.samples.entries())o.has(e.name)?r.push([]):r.push(null)}else for(const t of n.samples)r.push([])}for(const t of e.rglst)await j.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:t=>{const e=t.split("\t");for(const[t,n]of r.entries()){if(!n)continue;const r=Number(e[t+2]);Number.isFinite(r)&&n.push(r)}}});const o=[];for(const[t,i]of r.entries()){if(!i)continue;const r=(0,E.Z)(i,50),s={dt:I.dtcnv,value:r,samples:[{sample_id:n.samples[t].name}]};r>0&&r>(e.cnvGainCutoff\|\|.1)?s.class=I.mclasscnvgain:r<0&&r<(e.cnvLossCutoff\|\|-.1)&&(s.class=I.mclasscnvloss),s.class&&o.push(s)}return o}}(t,e),(0,C.uK)(t),function(t){if(!t.ssm2canonicalisoform)return;if(t.ssm2canonicalisoform.gdcapi)return void f.validate_ssm2canonicalisoform(t.ssm2canonicalisoform);throw"ssm2canonicalisoform.gdcapi is false"}(t),function(t,e){if(!e.genedb.hasTable_refseq2ensembl)return;t.refseq2ensembl_query=e.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?")}(t,e),function(t,e){if(!t.queries.snvindel&&!t.queries.svfusion&&!t.queries.geneCnv)return;t.mayGetGeneVariantData=async(n,r)=>{if("object"!=typeof n.term)throw"tw.term{} is not object";if("geneVariant"!=n.term.type)throw"tw.term.type is not geneVariant";if("string"!=typeof n.term.name)throw"tw.term.name is not string";if(!n.term.name)throw"tw.term.name should be gene symbol but is empty string";const o=[];if(t.queries.snvindel){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter};t.queries.geneCnv&&(o.useCaseid4sample=!0);if(t.queries.snvindel.byisoform)return await async function(t,e){if(t.isoform&&"string"==typeof t.isoform)return;if(!t.name)throw"both term.name and term.isoform";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)return;const r=n.find((t=>t.isdefault))\|\|n[0],o=JSON.parse(r.genemodel);if(!o.isoform)throw"isoform missing from returned gm";t.isoform=o.isoform}(e,n),e.isoform?(o.isoform=e.isoform,await t.queries.snvindel.byisoform.get(o)):[];if(t.queries.snvindel.byrange)return await ut(e,n),o.rglst=[e],await t.queries.snvindel.byrange.get(o);throw"unknown queries.snvindel method"}(t,n.term,e,r);o.push(...i)}if(t.queries.svfusion){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter};if(t.queries.svfusion.byrange)return await ut(e,n),o.rglst=[e],await t.queries.svfusion.byrange.get(o);throw"unknown queries.svfusion method"}(t,n.term,e,r);o.push(...i)}if(t.queries.cnv){const i=await async function(t,e,n,r){var o,i,s;const a={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,cnvMaxLength:null==e\|\|null===(o=e.q)\|\|void 0===o?void 0:o.cnvMaxLength,cnvGainCutoff:null==e\|\|null===(i=e.q)\|\|void 0===i?void 0:i.cnvGainCutoff,cnvLossCutoff:null==e\|\|null===(s=e.q)\|\|void 0===s?void 0:s.cnvLossCutoff};if(t.queries.cnv.byrange)return await ut(e.term,n),a.rglst=[e.term],await t.queries.cnv.byrange.get(a);throw"unknown queries.cnv method"}(t,n,e,r);o.push(...i)}if(t.queries.probe2cnv){const i=await async function(t,e,n,r){var o,i;const s={filter0:r.filter0,filterObj:r.filter,cnvGainCutoff:null==e\|\|null===(o=e.q)\|\|void 0===o?void 0:o.cnvGainCutoff,cnvLossCutoff:null==e\|\|null===(i=e.q)\|\|void 0===i?void 0:i.cnvLossCutoff};return await ut(e.term,n),s.rglst=[e.term],await t.queries.probe2cnv.get(s)}(t,n,e,r);o.push(...i)}if(t.queries.geneCnv){const e=await async function(t,e,n,r){const o={filter0:r.filter0};if(t.queries.geneCnv.bygene)return e.name?(o.gene=e.name,await t.queries.geneCnv.bygene.get(o)):[];throw"unknown queries.geneCnv method"}(t,n.term,0,r);o.push(...e)}const i=new Map;for(const e of o)if(Array.isArray(e.samples))for(const r of e.samples){var s,a;if(i.has(r.sample_id)\|\|i.set(r.sample_id,{sample:r.sample_id}),null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.termdb)&&void 0!==a&&a.additionalSampleAttributes)for(const e of t.cohort.termdb.additionalSampleAttributes)e in r&&(i.get(r.sample_id)[e]=r[e]);i.get(r.sample_id)[n.term.name]\|\|(i.get(r.sample_id)[n.term.name]={key:n.term.name,label:n.term.name,values:[]});const o={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,_SAMPLEID_:r.sample_id,_SAMPLENAME_:r.sample_id};if(r.__sampleName&&(o._SAMPLENAME_=r.__sampleName),"value"in e&&(o.value=e.value),r.formatK2v)for(const t in r.formatK2v)o[t]=r.formatK2v[t];e.dt==I.dtsnvindel\|\|e.dt!=I.dtfusionrna&&e.dt!=I.dtsv\|\|(o.pairlst=e.pairlst),t.cohort.termdb.q.id2sampleName&&Number.isInteger(r.sample_id)&&(o._SAMPLENAME_=t.cohort.termdb.q.id2sampleName(r.sample_id)),i.get(r.sample_id)[n.term.name].values.push(o)}return await async function(t,e,n,r){var o;if(null===(o=e.assayAvailability)\|\|void 0===o\|\|!o.byDt)return;const i=t.filter?new Set((await(0,P.get_samples)(t.filter,e)).map((t=>t.id))):null;for(const t in e.assayAvailability.byDt){const o=e.assayAvailability.byDt[t];if(o.byOrigin)for(const e in o.byOrigin){ct(t,o.byOrigin[e],n,r,e,i)}else ct(t,o,n,r,!1,i)}}(r,t,i,n.term.name),i}}(t,e)),function(t){if(!t.assayAvailability)return;if(t.assayAvailability.byDt)for(const e in t.assayAvailability.byDt){const n=t.assayAvailability.byDt[e];if(n.byOrigin)for(const e in n.byOrigin){const r=n.byOrigin[e];if(!r.yes\|\|!r.no\|\|!r.term_id)throw"ds.assayAvailability.byDt..byOrigin properties require .term_id .yes{} .no{}";ft(t,r)}else{if(!n.yes\|\|!n.no\|\|!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";ft(t,n)}}}(t),null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.db)&&void 0!==a&&a.refresh&&r&&(0,D.setDbRefreshRoute)(t,r,i)}function J(t){var e;const n={isMds3:!0,label:t.label};if(function(t,e){if(!t.queries)return;const n={};t.queries.singleSampleMutation&&(n.singleSampleMutation={sample_id_key:t.queries.singleSampleMutation.sample_id_key,discoSkipChrM:t.queries.singleSampleMutation.discoSkipChrM});if(t.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const e in t.queries.singleSampleGenomeQuantification)n.singleSampleGenomeQuantification[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGenomeQuantification[e])),delete n.singleSampleGenomeQuantification[e].folder}if(t.queries.singleSampleGbtk){n.singleSampleGbtk={};for(const e in t.queries.singleSampleGbtk)n.singleSampleGbtk[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGbtk[e])),delete n.singleSampleGbtk[e].folder}const r=t.queries.snvindel;r&&(e.has_skewer=!0,n.snvindel={forTrack:r.forTrack,vcfid4skewerName:r.vcfid4skewerName,variantUrl:r.variantUrl,skewerRim:r.skewerRim},r.m2csq&&(n.snvindel.m2csq={by:r.m2csq.by}),r.info&&(e.bcf={info:r.info}),r.format&&(e.bcf\|\|(e.bcf={}),e.bcf.format=r.format));if(t.queries.ld){n.ld=JSON.parse(JSON.stringify(t.queries.ld));for(const t of n.ld.tracks)delete t.file}e.queries=n}(t,n),null!==(e=t.cohort)&&void 0!==e&&e.termdb&&(n.termdb={},t.cohort.termdb.allowCaseDetails&&(n.termdb.allowCaseDetails={sample_id_key:t.cohort.termdb.allowCaseDetails.sample_id_key})),t.variant2samples){const e=t.variant2samples;n.variant2samples={sunburst_twLst:e.sunburst_twLst,twLst:e.twLst,type_samples:e.type_samples,type_summary:e.type_summary,type_sunburst:e.type_sunburst,url:e.url,variantkey:e.variantkey}}return n}async function H(t){var e,r,o,i;if(t.cohort){if(!t.cohort.termdb)throw"ds.cohort is set but cohort.termdb{} missing";if(!t.cohort.db)throw"ds.cohort is set but cohort.db{} missing";if(!t.cohort.db.file&&!t.cohort.db.file_fullpath)throw"ds.cohort.db.file missing"}else{if(!t.termdb)return;t.cohort={},t.cohort.termdb=t.termdb,delete t.termdb}const s=t.cohort.termdb;if(null!=s&&null!==(e=s.dictionary)&&void 0!==e&&e.gdcapi)await k(t);else if(null!=s&&null!==(r=s.dictionary)&&void 0!==r&&r.dbFile)t.cohort.db={file:s.dictionary.dbFile},delete s.dictionary.dbFile,(0,F.server_init_db_queries)(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";(0,F.server_init_db_queries)(t)}if(s.termid2totalsize2&&(s.termid2totalsize2.gdcapi,s.termid2totalsize2.get=async(e,n={},r=null)=>s.termid2totalsize2.gdcapi?await f.get_termlst2size(e,n,r,t):await async function(t,e,n,r){const o=Y(e,r),i=new Map;for(const e of t)if(e.term&&"categorical"==e.term.type){var s,a;const t={term1_id:e.id,term1_q:{type:"values"},filter:o},n=await(0,L.barchart_data)(t,r,r.cohort.termdb);if(null==n\|\|null===(s=n.data)\|\|void 0===s\|\|null===(a=s.charts)\|\|void 0===a\|\|!a[0])continue;const l=[];for(const t of n.data.charts[0].serieses)l.push([t.seriesId,t.total]);i.set(e.id,l)}return n?[i,n]:i}(e,n,r,t)),function(t){const e=t.selectCohort;if(!e)return;if("object"!=typeof e)throw"selectCohort{} not object";if(!e.term)throw"term{} missing from termdb.selectCohort";if(!e.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof e.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=e.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';{const n=t.q.termjsonByOneid(e.term.id);if(!n)throw"termdb.selectCohort.term.id is invalid";if("categorical"!=n.type)throw"termdb.selectCohort.term type is not categorical"}if(!e.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(e.values))throw"termdb.selectCohort.values is not array";if(0==e.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const t of e.values){if(!t.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(t.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==t.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}(s),await async function(t){if(!t.restrictAncestries)return;if(!Array.isArray(t.restrictAncestries)\|\|0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!e.tvs.term)throw"tvs.term{} missing from an ancestry";if(!e.tvs.term.id)throw"tvs.term.id missing from an ancestry";{const n=t.q.termjsonByOneid(e.tvs.term.id);if(!n)throw"tvs.term.id is invalid from an ancestry";if("categorical"!=n.type)throw"tvs.term.type is not categorical from an ancestry"}if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCfile)e.pcs=await V(e.PCfile,e.PCcount);else if(e.PCfileBySubcohort){if(!t.selectCohort)throw"PCfileBySubcohort is in use but selectCohort is not enabled";for(const n in e.PCfileBySubcohort){let r=!0;for(const e of t.selectCohort.values)if(n==e.keys.sort().join(",")){r=!1;break}if(r)throw"unknown subcohort from PCfileBySubcohort";const o=e.PCfileBySubcohort[n];if(!o.file)throw".file missing for a subcohort in PCfileBySubcohort";o.pcs=await V(o.file,e.PCcount)}}}}(s),await(0,z.wz)(t),await(0,B.mayInitiateMatrixplots)(t),"minTimeSinceDx"in s){if(!Number.isFinite(s.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(s.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in s){if(!Number.isFinite(s.ageEndOffset))throw"termdb.ageEndOffset not number";if(s.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(t.cohort.termdb.additionalSampleAttributes){if(!Array.isArray(t.cohort.termdb.additionalSampleAttributes))throw"termdb.additionalSampleAttributes not array";for(const e of t.cohort.termdb.additionalSampleAttributes)if("string"!=typeof e)throw"non-str key in termdb.additionalSampleAttributes[]"}if(s.convertSampleId){if(!s.convertSampleId.gdcapi)throw"unknown implementation of tdb.convertSampleId";f.convertSampleId_addGetter(s,t)}if(null!==(o=t.cohort)&&void 0!==o&&null!==(i=o.db)&&void 0!==i&&i.connection){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT * FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[r]=t.sampleId2Name.get(+r);return n}}if(t.cohort.mutationset){const{mayGetGeneVariantData:e,getTermTypes:r,mayGetMatchingGeneNames:o}=n(7833);t.mayGetGeneVariantData=e,t.getTermTypes=r,t.mayGetMatchingGeneNames=o}}async function V(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(G+t,new Map);let r=0;for(const o of(await j.read_file(l().join(g().tpmasterdir,t))).trim().split("\n")){r++;const t=o.split("\t"),i=Number(t[0]);if(!Number.isInteger(i))throw"non-integer sample id from a line of restrictAncestries pc file";for(let r=1;r<=e;r++){const e=G+r,o=Number(t[r]);if(Number.isNaN(o))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(i,o)}}return console.log(r,"samples loaded from "+t),Object.freeze(n)}function Y(t,e){const n=[];if(t.filterObj&&n.push(t.filterObj),t.tid2value&&n.push(rt(t.tid2value,e)),0!=n.length)return 1==n.length?n[0]:(0,R.filterJoin)(n)}function Q(t,e,n){var r;if(!e)return;let o;if(null!=t&&null!==(r=t.cohort)&&void 0!==r&&r.termdb){for(const t of e){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer sample id from "+n;t.name=e}o=", all integer IDs"}console.log(e.length,"samples from "+n+" of "+t.label+o)}async function K(t,e){var n;const r=t.queries.snvindel.byrange;if(r._tk.file)await j.init_one_vcf(r._tk,e,!0);else if(r._tk.chr2files){let t;for(const n in r._tk.chr2files){if("chr17"!=n)continue;const o=r._tk.chr2files[n];try{await j.init_one_vcf(o,e,!0);const i=JSON.stringify(o.samples);if(t){if(i!=t)throw"Different samples found in bcf file of "+n}else t=i,r._tk.samples=o.samples,r._tk.format=o.format,r._tk.info=o.info,r._tk.nochr=o.nochr}catch(t){console.log("missing file ignored:",o.file)}}}if(null!==(n=r._tk)&&void 0!==n&&n.samples.length){if(!r._tk.format)throw"bcf file has samples but no FORMAT"}else if(r._tk.format)throw"bcf file has FORMAT but no samples";if(r._tk.format){for(const t in r._tk.format)"GT"==t&&(r._tk.format[t].isGT=!0);if(t.queries.snvindel.format4filters){if(!Array.isArray(t.queries.snvindel.format4filters))throw"snvindel.format4filters[] is not array";for(const e of t.queries.snvindel.format4filters)r._tk.format[e]&&(r._tk.format[e].isFilter=!0);delete t.queries.snvindel.format4filters}}if(r._tk.info){if(r.infoFields){for(const t of r.infoFields){if(!t.key)throw".key missing from one of snvindel.byrange.infoFields[]";t.name\|\|(t.name=t.key);const e=r._tk.info[t.key];if(!e)throw"invalid key from one of snvindel.byrange.infoFields[]";e.categories=t.categories,e.name=t.name,e.separator=t.separator}delete r.infoFields}if(t.queries.snvindel.infoUrl){for(const e of t.queries.snvindel.infoUrl){const t=r._tk.info[e.key];if(!t)throw"invalid key from one of snvindel.infoUrl[]";t.urlBase=e.base}delete t.queries.snvindel.infoUrl}}return t.queries.snvindel.info=r._tk.info,t.queries.snvindel.format=r._tk.format,async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const n=X(e);let o;if(r._tk.chr2files){const t=r._tk.chr2files[e.rglst[0].chr];if(!t)throw"unknown chr for chr2files";o=t.file}else o=r._tk.file\|\|r._tk.url;const i=["query",o,"-r",e.rglst.map((t=>(r._tk.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1))).join(","),"-f","%ID\t%CHROM\t%POS\t%REF\t%ALT\t%INFO\t%FORMAT\n"],s=await nt(e,r._tk.samples,t);if(s){if(0==s.size)return[];i.push("-s",[...s].join(","))}e.variantFilter&&(0,$.add_bcf_variant_filter)(e.variantFilter,i);const a=[];return await j.get_lines_bigfile({isbcf:!0,args:i,dir:r._tk.dir,callback:o=>{const i=o.split("\t"),l=i[0],c=i[1],u=Number(i[2]),f=i[3],d=i[4].split(","),h=i[5],p={pos:u-1};(0,O.compute_mclass)(r._tk,f,d,p,h,l,e.isoform);for(const o of p.mlst){var m,g,y;e.hiddenmclass&&e.hiddenmclass.has(o.class)\|\|(tt(o,e)\|\|p.mlst.length>1&&null!==(m=e.variantFilter)&&void 0!==m&&m.lst&&et(o,e)\|\|(o.chr=(r._tk.nochr?"chr":"")+c,o.ssm_id=[o.chr,o.pos,o.ref,o.alt].join(Z),null!==(g=r._tk)&&void 0!==g&&null!==(y=g.samples)&&void 0!==y&&y.length&&(ot(r,o,i,e.addFormatValues,t,s,n),!o.samples)\|\|a.push(o)))}}}),a}}function X(t){var e,n;const r=t.formatFilter\|\|{};return"format"==(null===(e=t.skewerRim)\|\|void 0===e?void 0:e.type)&&null!==(n=t.skewerRim.hiddenvalues)&&void 0!==n&&n.size&&(r[t.skewerRim.formatKey]=t.skewerRim.hiddenvalues),Object.keys(r).length?r:void 0}function tt(t,e){if(!e.infoFilter)return!1;for(const n in e.infoFilter){const r=t.info[n];if(r)if(Array.isArray(r)){for(const t of e.infoFilter[n])if(r.includes(t))return!0}else if(e.infoFilter[n].includes(r))return!0}return!1}function et(t,e){for(const r of e.variantFilter.lst){const e=t.info[r.tvs.term.id];if(null==e)return!0;if("integer"==r.tvs.term.type\|\|"float"==r.tvs.term.type){var n;const t=Number(e);if(Number.isNaN(t))return!0;const o=null===(n=r.tvs.ranges)\|\|void 0===n?void 0:n[0];if(o){if("start"in o)if(o.startinclusive){if(t<o.start)return!0}else if(t<=o.start)return!0;if("stop"in o)if(o.stopinclusive){if(t>o.stop)return!0}else if(t>=o.stop)return!0}}}return!1}async function nt(t,e,n){if(!e)return;const r=function(t,e){if(t.filterObj){if(!Array.isArray(t.filterObj.lst))throw"filterObj.lst is not array";return 0==t.filterObj.lst.length?null:t.filterObj}if(t.tid2value){if("object"!=typeof t.tid2value)throw"q.tid2value{} not object";return rt(t.tid2value,e)}}(t,n);if(!r)return;const o=[...new Set((await(0,P.get_samples)(r,n)).map((t=>t.id)))],i=new Set(e.map((t=>t.name))),s=new Set;for(const t of o)i.has(t)&&s.add(t);return s}function rt(t,e){const n={type:"tvslst",in:!0,join:"and",lst:[]};for(const r in t){const o=e.cohort.termdb.q.termjsonByOneid(r);if(!o)continue;const i=t[r];n.lst.push({type:"tvs",tvs:{term:o,values:[{key:i}]}})}return n}function ot(t,e,n,r,o,i,s){if(!n[6]\|\|"."==n[6])return;const a=[];for(const e of n[6].split(":")){const n=t._tk.format[e];if(!n)throw"invalid format field: "+n;a.push(n)}const l=[];let c=t._tk.samples;i&&(c=[...i].map((t=>({name:t}))));for(const[t,e]of c.entries()){const o=n[t+7];if(!o\|\|"."==o)continue;const i=it(o.split(":"),a,e,r);if(i){if(s){let t=!1;for(const e in s){const n=e in i.formatK2v?i.formatK2v[e]:U;if(s[e].has(n)){t=!0;break}}if(t)continue}l.push(i)}}l.length&&(e.samples=l)}function it(t,e,n,r){const o={};for(const[n,r]of e.entries()){const e=t[n];if(e&&"."!=e)if(r.isGT){if("./."==e\|\|".\|."==e)continue;o.GT=e}else o[r.ID]=e}if(0==Object.keys(o).length)return null;const i={sample_id:n.name};return r&&(i.formatK2v=o),i}function st(t,e,n,r=1){r=Number(r);const i=200,a=20;let l=0;for(const t in e.majorchr)l+=e.majorchr[t];const f=800/l,d={};let h=0;const p=[];for(const t in e.majorchr){const n=e.majorchr[t];d[t]=(0,c.Z)().domain([0,n]).range([fh,f(h+n)]),h+=n,p.push({chr:t,chrLen:n,xStart:f(h-n),xStop:fh})}const m=(0,c.Z)().domain([n.min,n.max]).range([i,0]),g=(0,u.createCanvas)(890r,240r),y=g.getContext("2d");r>1&&y.scale(r,r),b(n.max),b(0),b(n.min);const v=s().createInterface({input:o().createReadStream(t)});return new Promise(((t,r)=>{v.on("line",(t=>{const e=t.split("\t"),r=e[0];if(!r)return;if(!d[r])return;const o=Number(e[1]);if(!Number.isInteger(o))return;const i=Number(e[2]);if(!Number.isFinite(i))return;if(i<n.min\|\|i>n.max)return;y.fillStyle=i>0?n.positiveColor:n.negativeColor;const s=d[r](o),l=a+m(i);y.fillRect(70+s,l,1,1)})),v.on("close",(()=>{!function(){y.strokeStyle="black",y.beginPath();{const t=220-m(0);y.moveTo(70,t),y.lineTo(870,t),y.stroke()}let t=!0;y.fillStyle="black",y.font="12px Arial",y.textAlign="center";for(const n in d){if(y.fillText(n.replace("chr",""),70+d[n](e.majorchr[n]/2),234),t){t=!1;continue}const r=Math.floor(70+d[n](0))+.5;y.moveTo(r,a),y.lineTo(r,220),y.stroke()}y.closePath()}(),t({src:g.toDataURL(),canvasWidth:890,canvasHeight:240,xoff:70,chrLst:p})}))}));function b(t){y.fillStyle="black",y.font="12px Arial",y.textAlign="right";const e=a+m(t);y.fillText(t,64,e+5),y.strokeStyle="black",y.beginPath(),y.moveTo(66,e),y.lineTo(70,e),y.stroke(),y.closePath()}}async function at(t,e){const n=t.queries.svfusion.byrange;if(n.file)await j.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on svfusion.byrange{}";n.dir=await j.cache_index(n.url,n.indexURL)}n.nochr=await j.tabix_is_nochr(n.file\|\|n.url,null,e);{const t=await j.get_header_tabix(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}return async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const r=X(e),o=await nt(e,n.samples,t);if(0==(null==o?void 0:o.size))return[];const i=new Map;for(const t of e.rglst)await j.get_lines_bigfile({args:[n.file\|\|n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const s=n.split("\t"),a=Number(s[1]);let l,c,u,f,d;try{l=JSON.parse(s[3])}catch(t){return}if(l.dt!=I.dtfusionrna&&l.dt!=I.dtsv)return;if(l.class=l.dt==I.dtsv?I.mclasssv:I.mclassfusionrna,e.hiddenmclass&&e.hiddenmclass.has(l.class))return;if(l.sample&&o&&!o.has(l.sample))return;if(l.chrA)c=1,u=l.geneA\|\|l.chrA,f=l.strandA,d=[{a:{chr:l.chrA,pos:l.posA,strand:l.strandA,name:l.geneA},b:{chr:t.chr,pos:a,strand:l.strandB,name:l.geneB}}];else if(l.chrB)c=0,u=l.geneB\|\|l.chrB,f=l.strandB,d=[{a:{chr:t.chr,pos:a,strand:l.strandA,name:l.geneA},b:{chr:l.chrB,pos:l.posB,strand:l.strandB,name:l.geneB}}];else{if(!l.pairlst)throw"missing chrA and chrB";{d=l.pairlst;const t=l.pairlst.findIndex((t=>t.chr==chr&&t.pos==a));if(-1==t)throw"current point missing from pairlst";c=t}}const h=[l.dt,t.chr,a,f,c,encodeURIComponent(u)].join(Z);let p;if(l.sample&&(p={sample_id:l.sample},l.mattr)){if(r)for(const t in r){const e=t in l.mattr?l.mattr[t]:U;if(r[t].has(e))return}e.addFormatValues&&(p.formatK2v=l.mattr)}i.has(h)\|\|i.set(h,{ssm_id:h,dt:l.dt,class:l.class,chr:t.chr,pos:a,strand:f,pairlstIdx:c,mname:u,pairlst:d,samples:[]}),p&&i.get(h).samples.push(p)}});return[...i.values()]}}async function lt(t,e){const n=t.queries.cnv.byrange;if(n.file)await j.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on cnv.byrange{}";n.dir=await j.cache_index(n.url,n.indexURL)}n.nochr=await j.tabix_is_nochr(n.file\|\|n.url,null,e);{const t=await j.get_header_tabix(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}return async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";if(e.cnvMaxLength&&!Number.isInteger(e.cnvMaxLength))throw"cnvMaxLength is not integer";if(e.cnvGainCutoff&&!Number.isFinite(e.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(e.cnvLossCutoff&&!Number.isFinite(e.cnvLossCutoff))throw"cnvLossCutoff is not finite";const r=X(e),o=await nt(e,n.samples,t);if(0==(null==o?void 0:o.size))return[];const i=[],s=[];for(const t of e.rglst)s.push(j.get_lines_bigfile({args:[n.file\|\|n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const s=n.split("\t"),a=Number(s[1]),l=Number(s[2]);if(e.cnvMaxLength&&l-a>=e.cnvMaxLength)return;let c;try{c=JSON.parse(s[3])}catch(t){return}if(c.dt==I.dtcnv){if(c.start=a,c.stop=l,Number.isFinite(c.value)){if(c.value>0&&e.cnvGainCutoff&&c.value<e.cnvGainCutoff)return;if(c.value<0&&e.cnvLossCutoff&&c.value>e.cnvLossCutoff)return;c.class=c.value>0?I.mclasscnvgain:I.mclasscnvloss}else if(c.class!=I.mclasscnvgain&&c.class!=I.mclasscnvloss)return;if(c.ssm_id=[t.chr,c.start,c.stop,c.class].join(Z),(!e.hiddenmclass\|\|!e.hiddenmclass.has(c.class))&&(!c.sample\|\|!o\|\|o.has(c.sample))){if(c.sample){const t={sample_id:c.sample};if(c.mattr){if(r)for(const t in r){const e=t in c.mattr?c.mattr[t]:U;if(r[t].has(e))return}e.addFormatValues&&(t.formatK2v=c.mattr)}delete c.sample,c.samples=[t]}i.push(c)}}}}));return await Promise.all(s),i}}function ct(t,e,n,r,o,i){for(const s of e.yesSamples){if(i&&!i.has(s))continue;n.has(s)\|\|n.set(s,{sample:s});const e=n.get(s);r in e\|\|(e[r]={key:r,values:[],label:r}),o?e[r].values.some((e=>e.dt==t&&e.origin==o))\|\|e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:s,origin:o}):e[r].values.some((e=>e.dt==t))\|\|e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:s})}for(const s of e.noSamples){if(i&&!i.has(s))continue;n.has(s)\|\|n.set(s,{sample:s});const e=n.get(s);r in e\|\|(e[r]={key:r,values:[],label:r}),o?e[r].values.some((e=>e.dt==t&&e.origin==o))\|\|e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:s,origin:o}):e[r].values.some((e=>e.dt==t))\|\|e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:s})}}async function ut(t,e){if(t.chr&&Number.isInteger(t.start)&&Number.isInteger(t.stop))return;if(!t.name)throw"both term.name and term.chr/start/stop missing";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)throw"unknown gene name";const r=n.find((t=>t.isdefault))\|\|n[0],o=JSON.parse(r.genemodel);if(!o.chr\|\|!Number.isInteger(o.start)\|\|!Number.isInteger(o.stop))throw"invalid chr/start/stop from returned gm";t.chr=o.chr,t.start=o.start,t.stop=o.stop}function ft(t,e){e.yesSamples=new Set,e.noSamples=new Set;const n=`SELECT sample, value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = '${e.term_id}'`,r=t.cohort.db.connection.prepare(n).all();for(const t of r)e.yes.value.includes(t.value)?e.yesSamples.add(t.sample):e.no.value.includes(t.value)&&e.noSamples.add(t.sample)}},8089:(t,e,n)=>{"use strict";n.d(e,{f:()=>u});const r=n(9699),o=n(7147),i=n(1017),s=n(2081).spawn,a=n(3856),l=n(334),c=n(9191).snvindelByRangeGetter_bcf;n(1271).run_rust;function u(t){return async(e,n)=>{try{if(!e.query.genome)throw".genome missing";const o=t[e.query.genome];if(!o)throw"invalid genome";const i=function(t,e){const n=t.query;t.get("X-Auth-Token")&&(n.token=t.get("X-Auth-Token"));t.cookies.sessionid&&(n.sessionid=t.cookies.sessionid);n.hiddenmclasslst&&(n.hiddenmclass=new Set(n.hiddenmclasslst.split(",")),delete n.hiddenmclasslst);return n}(e),s=await async function(t,e){if(t.dslabel){if(!e.datasets)throw".datasets{} missing from genome";const n=e.datasets[t.dslabel];if(!n)throw"invalid dslabel";return n}const n={queries:{}};if(t.bcffile\|\|t.bcfurl){const[o,i,s]=r.fileurl({query:{file:t.bcffile,url:t.bcfurl}});if(o)throw o;const a={};s?(a.url=i,a.indexURL=t.bcfindexURL):a.file=i,n.queries.snvindel={byrange:{_tk:a}},n.queries.snvindel.byrange.get=await c(n,e)}return n}(i,o);!function(t,e){var n;if(t.filter0){const n="object"==typeof t.filter0?t.filter0:JSON.parse("string"==typeof t.filter0&&t.filter0.startsWith("%")?decodeURIComponent(t.filter0):t.filter0);t.filter0=e.validate_filter0(n)}t.filterObj&&"string"==typeof t.filterObj&&(t.filterObj=JSON.parse("string"==typeof t.filterObj&&t.filterObj.startsWith("%")?decodeURIComponent(t.filterObj):t.filterObj));if(t.skewerRim){if("format"!=t.skewerRim.type)throw"unknown skewerRim.type";var r,o;if(!t.skewerRim.formatKey)throw"skewerRim.formatKey missing when type=format";if(null===(r=e.queries)\|\|void 0===r\|\|null===(o=r.snvindel)\|\|void 0===o\|\|!o.format)throw"snvindel.format{} not found when type=format";if(!e.queries.snvindel.format[t.skewerRim.formatKey])throw"invalid skewerRim.formatKey";if(t.skewerRim.hiddenvalues=new Set,t.skewerRim.hiddenvaluelst){if(!Array.isArray(t.skewerRim.hiddenvaluelst))throw"query.skewerRim.hiddenvaluelst is not array";for(const e of t.skewerRim.hiddenvaluelst)t.skewerRim.hiddenvalues.add(e);delete t.skewerRim.hiddenvaluelst}}if(t.formatFilter){var i,s;if("object"!=typeof t.formatFilter)throw"formatFilter{} not object";if(null===(i=e.queries)\|\|void 0===i\|\|null===(s=i.snvindel)\|\|void 0===s\|\|!s.format)throw"snvindel.format{} not found when formatFilter is used";const n={};for(const r in t.formatFilter){if(!e.queries.snvindel.format[r])throw"invalid format key from formatFilter";if(!Array.isArray(t.formatFilter[r]))throw"formatFilter[k] value is not array";n[r]=new Set(t.formatFilter[r])}t.formatFilter=n}("format"==(null===(n=t.skewerRim)\|\|void 0===n?void 0:n.type)\|\|t.formatFilter)&&(t.addFormatValues=!0)}(i,s);const a=await async function(t,e){if(t.singleSampleMutation){var n;if(null===(n=e.queries.singleSampleMutation)\|\|void 0===n\|\|!n.get)throw"not supported on this dataset";return{mlst:await e.queries.singleSampleMutation.get(t.singleSampleMutation,t)}}if(t.singleSampleGenomeQuantification){if(!e.queries.singleSampleGenomeQuantification)throw"not supported on this dataset";const n=e.queries.singleSampleGenomeQuantification[t.singleSampleGenomeQuantification.dataType];if(!n)throw"invalid dataType";return await n.get(t.singleSampleGenomeQuantification.sample,t.devicePixelRatio)}if(t.singleSampleGbtk){if(!e.queries.singleSampleGbtk)throw"not supported on this dataset";const n=e.queries.singleSampleGbtk[t.singleSampleGbtk.dataType];if(!n)throw"invalid dataType";return await n.get(t.singleSampleGbtk.sample)}if(t.ssm2canonicalisoform){if(!e.ssm2canonicalisoform)throw"ssm2canonicalisoform not supported on this dataset";return{isoform:await e.ssm2canonicalisoform.get(t)}}if(t.variant2samples){if(!e.variant2samples)throw"not supported by server";return{variant2samples:await e.variant2samples.get(t)}}if(t.m2csq){if(e.queries&&e.queries.snvindel&&e.queries.snvindel.m2csq)return{csq:await e.queries.snvindel.m2csq.get(t)};throw"m2csq not supported on this dataset"}if(t.forTrack){const n={};if(t.skewer){if(n.skewer=[],e.queries.snvindel){const r=await async function(t,e){if(t.isoform){if(t.atgenomic){if(!e.queries.snvindel.byrange)throw".atgenomic but missing byrange query method";return await e.queries.snvindel.byrange.get(t)}if(e.queries.snvindel.byisoform)return await e.queries.snvindel.byisoform.get(t)}if(t.rglst){if(!e.queries.snvindel.byrange)throw"q.rglst[] provided but .byrange{} is missing";return await e.queries.snvindel.byrange.get(t)}throw"insufficient query parameters for snvindel"}(t,e);n.skewer.push(...r)}if(e.queries.svfusion){const r=await async function(t,e){if(t.rglst){if(!e.queries.svfusion.byrange)throw"q.rglst provided but svfusion.byrange missing";return await e.queries.svfusion.byrange.get(t)}throw"insufficient query parameters for 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e){t.find((t=>t.chr==n.chr&&t.pos==n.pos&&t.ref==n.ref&&t.alt==n.alt))\|\|(n.groupData=[{refCount:0,altCount:0},{refCount:n._refCount,altCount:n._altCount}],i.push(n))}return i}(i.mlst,s.mlst,t);return{mlst:u,totalSampleCount_group1:a(i.mlst),totalSampleCount_group2:a(s.mlst)}}n.filterObj=c(t);const i=await e.queries.snvindel.byrange.get(n),s=l(i);"filter"==r.type?s.totalSampleCount_group1=a(i):"filter"==(null==o?void 0:o.type)&&(s.totalSampleCount_group2=a(i));return s}(t,n);if(1==t.details.groups.length)u(n,i.mlst,t.details.groups[0]);else{if(2!=t.details.groups.length)throw"q.details.groups.length not 1 or 2";await async function(t,e,n){const[r,i]=e.groups;if("filter"==r.type&&"filter"==i.type)return void await async function(t,e,n){const r=e.groupTestMethods[e.groupTestMethodsIdx];if(!r)throw"details.groupTestMethodsIdx out of bound";switch(r.name){case"Allele frequency difference":return void d(t,e,n);case"Fisher's exact test":return void await m(n);default:throw"unknown value 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r.sets)e+=Number(t.info[o.infokey_AC]\|\|0),n+=Number(t.info[o.infokey_AN]\|\|0);t.nm_axis_value=e/n}}}else{if(!n.infoKey)throw"infoKey missing on single group.type=info";for(const t of e){const e=t.info[n.infoKey];if(null==e);else{const n=Number(e);Number.isNaN(n)\|\|(t.nm_axis_value=n)}}}else for(const t of e)t.nm_axis_value=Number((t._altCount/(t._altCount+t._refCount)).toPrecision(2))}function f(t){let e=0,n=0;for(const o of t.samples){var r;if(null==o\|\|null===(r=o.formatK2v)\|\|void 0===r\|\|!r.GT)continue;const i=o.formatK2v.GT.split("/").map(Number);n+=i.length;for(const n of i)n==t.altAlleleIdx&&e++}return[e,n]}function d(t,e,n){const[r,o]=e.groups;u(t,n,r);const i=n.map((t=>t.nm_axis_value));u(t,n,o);for(const[t,e]of n.entries())e.nm_axis_value=i[t]-e.nm_axis_value}function h(t,e,n,r){const o=[];for(const i of e.groups)if("info"!=i.type)if("filter"!=i.type){if("population"!=i.type)throw"unknown group.type";{if(!i.key)throw"group.key missing for type=population";const e=t.queries.snvindel.populations.find((t=>t.key==i.key));if(!e)throw"invalid group.key for population";const s=new Map;for(const t of e.sets)s.set(t.key,{ACraw:Number(n.info[t.infokey_AC]\|\|0),ANraw:Number(n.info[t.infokey_AN]\|\|0)});let a=0,l=0;if(i.adjust_race)[a,l]=p(s,r);else for(const t of s.values())l+=t.ACraw,a+=t.ANraw-t.ACraw;o.push({altCount:l,refCount:a})}}else o.push({altCount:n._altCount,refCount:n._refCount});else{if(!i.key)throw"group.key missing for type=info";o.push({value:n.info[i.key]})}return o}function p(t,e){let n=0;for(const e of t.values())n+=e.ANraw;let r=0,o=0;for(const[i,s]of t)s.ANadj=ne.get(i).average,s.ACadj=0==s.ANadj?0:s.ACraws.ANadj/s.ANraw,r+=s.ACadj,o+=s.ANadj;return[o-r,r]}async function m(t){for(let e=0;e<Math.ceil(t.length/200);e++){const n=[];for(let r=200e;r<200(e+1);r++){const e=t[r];if(!e)break;const o=e.groupData;o&&o[0]&&o[1]&&Number.isFinite(o[0].altCount)&&Number.isFinite(o[0].refCount)&&Number.isFinite(o[1].altCount)&&Number.isFinite(o[1].refCount)?(n.push({index:r,n1:o[0].altCount,n2:o[0].refCount,n3:Math.floor(o[1].altCount),n4:Math.floor(o[1].refCount)}),e.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>${o[0].altCount}</td>\n\t\t\t\t <td>${Math.floor(o[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>${o[0].refCount}</td>\n\t\t\t\t <td>${Math.floor(o[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>${(o[0].altCount/(o[0].altCount+o[0].refCount)).toFixed(3)}</td>\n\t\t\t\t <td>${(o[1].altCount/(o[1].altCount+o[1].refCount)).toFixed(3)}</td>\n\t\t\t\t</tr>\n\t\t\t\t</table>`}]):console.log(`${e.chr}.${e.pos}.${e.ref}.${e.alt}\t${JSON.stringify(o)}`)}const r=await i("fisher",JSON.stringify({input:n}));for(const e of JSON.parse(r)){const n=t[e.index];n&&(n.p_value=e.p_value.toPrecision(2),e.p_value>0&&(n.nm_axis_value=Number((-Math.log10(e.p_value)).toPrecision(2))))}}let e=0;for(const n of t)n.p_value>0&&(e=Math.max(e,n.nm_axis_value));for(const n of t)0==n.p_value&&(n.nm_axis_value=Math.max(50,e))}},817:(t,e,n)=>{"use strict";n.d(e,{uK:()=>f,z9:()=>d});const{stratinput:r}=n(1881),{querySamples_gdcapi:o}=n(5243),{get_densityplot:i}=n(9402),{ssmIdFieldsSeparator:s}=n(9191),{dtfusionrna:a,dtsv:l}=(n(3856),n(2273)),c=n(4065),{getSampleData_dictionaryTerms_termdb:u}=n(2974);function f(t){const e=t.variant2samples;if(e){if(e.type_samples="samples",e.type_sunburst="sunburst",e.type_summary="summary",!e.variantkey)throw".variantkey missing from 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r){if(n.id0){if(!n.v0)continue;a.get(n.id0).add(e.cohort.termdb.useLower?n.v0.toLowerCase():n.v0)}if(n.id1&&t[1]){if(!n.v1)continue;a.get(n.id1).add(e.cohort.termdb.useLower?n.v1.toLowerCase():n.v1)}if(n.id2&&t[2]){if(!n.v2)continue;a.get(n.id2).add(e.cohort.termdb.useLower?n.v2.toLowerCase():n.v2)}}const c=t[0].id;{const r={};n.filterObj&&(r.filterObj=n.filterObj);const o=await e.cohort.termdb.termid2totalsize2.get([t[0]],r);for(const[t,n]of o.get(c)){const r=e.cohort.termdb.useLower?t.toLowerCase():t;l?(a.get(c).add(r),s.push({count:n,id0:c,v0:r})):a.get(c).has(r)&&s.push({count:n,id0:c,v0:r})}}const u=null==t\|\|null===(o=t[1])\|\|void 0===o?void 0:o.id;if(u){const r=[];for(const o of a.get(c)){const i={tid2value:{[c]:o}};n.filterObj&&(i.filterObj=n.filterObj),r.push(e.cohort.termdb.termid2totalsize2.get([t[1]],i,o))}const o=await Promise.all(r);for(const[t,n]of o)for(const[r,o]of t.get(u)){const t=e.cohort.termdb.useLower?r.toLowerCase():r;l?(a.get(u).add(t),s.push({count:o,id0:c,v0:n,id1:u,v1:t})):a.get(u).has(t)&&s.push({count:o,id0:c,v0:n,id1:u,v1:t})}}const f=null==t\|\|null===(i=t[2])\|\|void 0===i?void 0:i.id;if(f){const r=[];for(const o of a.get(c))for(const i of a.get(u)){const s={tid2value:{[c]:o,[u]:i}};n.filterObj&&(s.filterObj=n.filterObj),r.push(e.cohort.termdb.termid2totalsize2.get([t[2]],s,{v0:o,v1:i}))}const o=await Promise.all(r);for(const[t,n]of o)for(const[t,r]of v2counts.get(f)){const o=e.cohort.termdb.useLower?t.toLowerCase():t;l?(a.get(f).add(o),s.push({count:r,id0:c,v0:n.v0,id1:u,v1:n.v1,id2:f,v2:o})):a.get(f).has(o)&&s.push({count:r,id0:c,v0:n.v0,id1:u,v1:n.v1,id2:f,v2:o})}}return s}(n.twLst,e,n,s);await async function(t,e,n){for(const r of t){if(!r.id0)continue;if(!r.v0)continue;const t=n.cohort.termdb.useLower?r.v0.toLowerCase():r.v0;if(!r.id1){const n=e.find((e=>null==e.id1&&e.v0==t));n&&(r.cohortsize=n.count);continue}if(!r.v1)continue;const 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async function(t,e,n,r,o){var i,s,a,l,c,u;if(!t.tid)throw".tid missing";const f="geneVariant"==t.type?{name:t.tid,type:"geneVariant",isleaf:!0}:n.q.termjsonByOneid(t.tid),d={filter:t.filter,terms:"geneVariant"==t.type?[{term:f,q:{isAtomic:!0}}]:[{id:t.tid,term:f,q:t.term1_q\|\|A(f,t)}],currentGeneNames:t.currentGeneNames},h=await w(d,r,o);if(h.error)throw h.error;const p=[];if("geneVariant"==t.type){var m;const e=h.samples,n=new Map;if(null!==(m=r.assayAvailability)&&void 0!==m&&m.byDt)for(const[t,e]of Object.entries(r.assayAvailability.byDt))e.byOrigin&&n.set(parseInt(t),{byOrigin:{germline:{},somatic:{}}});for(const[r,o]of Object.entries(e)){const e=o[t.tid].values;for(const t of e){n.has(t.dt)\|\|n.set(t.dt,{});const e=n.get(t.dt);e.byOrigin?e.byOrigin[t.origin][t.class]=e.byOrigin[t.origin][t.class]?e.byOrigin[t.origin][t.class]+1:1:e[t.class]=e[t.class]?e[t.class]+1:1}}for(const[t,e]of n)p.push({dt:t,classes:e})}else{const e=new Map;for(const n in h.samples){const r=h.samples[n][t.tid];r&&("key"in r&&e.set(r.key,1+(e.get(r.key)\|\|0)))}for(const[n,r]of e){var y,v,b,_,x,k;p.push({samplecount:r,key:n,label:(null===(y=h.refs)\|\|void 0===y\|\|null===(v=y.byTermId)\|\|void 0===v\|\|null===(b=v[t.tid])\|\|void 0===b\|\|null===(_=b.events)\|\|void 0===_?void 0:_.find((t=>t.event===n)).label)\|\|(null==f\|\|null===(x=f.values)\|\|void 0===x\|\|null===(k=x[n])\|\|void 0===k?void 0:k.label)\|\|n})}}const q=g(f,(null===(i=h.refs)\|\|void 0===i\|\|null===(s=i.byTermId)\|\|void 0===s\|\|null===(a=s[t.tid])\|\|void 0===a?void 0:a.bins)\|\|[],null===(l=h.refs)\|\|void 0===l\|\|null===(c=l.byTermId)\|\|void 0===c\|\|null===(u=c[t.tid])\|\|void 0===u?void 0:u.events,t.term1_q);q.length&&p.sort(((t,e)=>q.indexOf(t.label)-q.indexOf(e.label)));e.send({lst:p,orderedLabels:q})}(s,n,T,M,N);if(s.getpercentile)return async function(t,e,n){const r=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!r)throw"invalid termid";if("float"!=r.type&&"integer"!=r.type)throw"not 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f=a.length,d=a.reduce(((t,e)=>t+e),0)/f,h=(0,o.Z)(a,25),p=(0,o.Z)(a,50),m=(0,o.Z)(a,75),g=a.map((t=>(t-d)*2)).reduce(((t,e)=>t+e),0)/(a.length-1),y=Math.sqrt(g),v=Math.min(...a),b=Math.max(...a);e.send({values:[{id:"total",label:"n",value:f},{id:"min",label:"Minimum",value:(0,r.Z)(v,2)},{id:"p25",label:"1st quartile",value:(0,r.Z)(h,2)},{id:"median",label:"Median",value:(0,r.Z)(p,2)},{id:"mean",label:"Mean",value:(0,r.Z)(d,2)},{id:"p75",label:"3rd quartile",value:(0,r.Z)(m,2)},{id:"max",label:"Maximum",value:(0,r.Z)(b,2)},{id:"sd",label:"Standard deviation",value:(0,r.Z)(y,2)}]})}(s,n,M);if(s.getnumericcategories)return await async function(t,e,n,r){if(!t.tid)throw".tid missing";n.q.termjsonByOneid(t.tid);const o={ds:r,term_id:t.tid};t.filter&&(o.filter=t.filter);const i=await u.get_summary_numericcategories(o);e.send({lst:i})}(s,n,T,M);if(s.default_rootterm)return await async function(t,e,n){const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"";e.send({lst:await n.q.getRootTerms(r,o)})}(s,n,T);if(s.get_children)return await async function(t,e,n){if(!t.tid)throw"no parent term id";const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"",i=await n.q.getTermChildren(t.tid,r,o);e.send({lst:i.map(S)})}(s,n,T);if(s.findterm)return await async function(t,e,n,r,o){var i;const s={equals:[],startsWith:[],startsWord:[],includes:[]},a=decodeURIComponent(t.findterm).toUpperCase(),c=y({type:"geneVariant"},t.usecase).has("plot");r.mayGetMatchingGeneNames&&c&&await r.mayGetMatchingGeneNames(s,a,t);const u=[];if(null!==(i=r.queries)&&void 0!==i&&i.defaultBlock2GeneMode&&c){const t=(0,l.getResult)(o,{input:a});if(Array.isArray(t.hits))for(let e=0;e<7&&t.hits[e];e++)u.push({name:t.hits[e],type:"geneVariant"})}"string"!=typeof t.cohortStr&&(t.cohortStr="");const f=await n.q.findTermByName(a,q,t.cohortStr,t.treeFilter,t.usecase,s);u.push(...f.map(S));u.forEach((t=>{"geneVariant"!=t.type&&(t.__ancestors=n.q.getAncestorIDs(t.id),t.__ancestorNames=n.q.getAncestorNames(t.id))})),e.send({lst:u})}(s,n,T,M,N);if(s.getterminfo)return function(t,e,n){if(!t.tid)throw"no term id";e.send({terminfo:n.q.getTermInfo(t.tid)})}(s,n,T);if(s.phewas)return s.update?await f.update_image(s,n):s.getgroup?await f.getgroup(s,n):await f.trigger(s,n,M);if(s.gettermdbconfig)return c.make(s,n,M,N);if(s.getcohortsamplecount)return n.send({count:M.cohort.termdb.q.getcohortsamplecount(s.cohort)});if(s.getsamplecount)return n.send(await async function(t,e,n){const r=a().canDisplaySampleIds(t,n);if("list"==e.getsamplecount){return await u.get_samples(e.filter,n,r)}return await u.get_samplecount(e,n)}(e,s,M));if(s.getsamples)return await async function(t,e,n){const r=await u.get_samples(t.filter,n),o=r.map((t=>n.cohort.termdb.q.id2sampleName(t)));e.send({samples:o})}(s,n,M);if(s.getcuminc)return await async function(t,e,n){const r=await d.get_incidence(t,n);e.send(r)}(s,n,M);if(s.getsurvival)return await async function(t,e,n){const r=await h.get_survival(t,n);e.send(r)}(s,n,M);if(s.getregression)return await async function(t,e,n){const r=await p.get_regression(t,n);e.send(r)}(s,n,M);if(s.validateSnps)return n.send(await m.validate(s,T,M,N));if(s.getvariantfilter)return function(t,e){var n,r;if(e.track)return void t.send(e.track.variant_filter);t.send((null==e\|\|null===(n=e.queries)\|\|void 0===n\|\|null===(r=n.snvindel)\|\|void 0===r?void 0:r.variant_filter)\|\|{})}(n,M);if(s.getLDdata)return await async function(t,e,n){var r,o;if(!t.ldtkname)throw".ldtkname missing";if(null===(r=e.queries)\|\|void 0===r\|\|null===(o=r.ld)\|\|void 0===o\|\|!o.tracks)throw"no ld tk";const s=e.queries.ld.tracks.find((e=>e.name==t.ldtkname));if(!s)throw"unknown ld tk";if("object"!=typeof t.m)throw"q.m{} not object";if(!t.m.chr)throw"q.m.chr missing";if(!Number.isInteger(t.m.pos))throw"q.m.pos not integer";if(!t.m.ref\|\|!t.m.alt)throw"q.m{} invalid alleles";const a=t.m.ref+"."+t.m.alt,l=(s.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+t.m.pos+"-"+(t.m.pos+1),c=[];await(0,i.get_lines_bigfile)({args:[s.file,l],dir:s.dir,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),i=n[3],s=n[4],l=Number.parseFloat(n[5]);r==t.m.pos&&i==a?c.push({pos:o,alleles:s,r2:l}):o==t.m.pos&&s==a&&c.push({pos:r,alleles:i,r2:l})}}),n.send({lst:c})}(s,M,n);if(s.genesetByTermId)return function(t,e,n){if(!n.termMatch2geneSet)throw"this feature is not enabled";if("string"!=typeof t.genesetByTermId\|\|0==t.genesetByTermId.length)throw"invalid query term id";const r=n.q.getGenesetByTermId(t.genesetByTermId);e.send(r)}(s,n,T);if(s.getSampleScatter)return await v(e,s,n,M,N);if(s.getLowessCurve)return await b(e,s,n);if(s.getCohortsData)return await x(s,n,M);if(s.getViolinPlotData)return await _(s,n,M,N);if("mds3queryDetails"==s.for)return function(t,e){const n={},r=e.queries\|\|{};r.snvindel&&(n.snvindel={},r.snvindel.details&&(n.snvindel.details=r.snvindel.details),r.snvindel.populations&&(n.snvindel.populations=r.snvindel.populations));r.trackLst&&(n.trackLst=r.trackLst);if(r.ld){n.ld=JSON.parse(JSON.stringify(r.ld));for(const t of n.ld.tracks)delete t.file}t.send(n)}(n,M);if("termTypes"==s.for)return n.send(await M.getTermTypes(s));if("matrix"==s.for)return await async function(t,e,n,r,o){if(t.getPlotDataByName){if(!r.cohort.matrixplots)throw"ds.cohort.matrixplots missing for the dataset";if(!r.cohort.matrixplots.plots)throw"ds.cohort.matrixplots.plots missing for the dataset";const e=r.cohort.matrixplots.plots.find((e=>e.name===t.getPlotDataByName));if(!e)throw`plot name: q.getPlotDataByName=${getPlotDataByName} missing in ds.cohort.matrixplots.plots`;return void n.send(e.matrixConfig)}const i=await w(t,r,o);if(a().canDisplaySampleIds(e,r))for(const t of Object.values(i.samples))t.sampleName=r.sampleId2Name.get(t.sample);n.send(i)}(s,e,n,M,N);if("mds3variantData"==s.for)return await k(s,n,M,N);if(s.for,"convertSampleId"==s.for)return function(t,e,n){if(!n.convertSampleId)throw"not supported on this ds";if(!Array.isArray(t.inputs))throw"q.inputs[] not array";e.send({mapping:n.convertSampleId.get(t.inputs)})}(s,n,T);throw"termdb: doesn't know what to do"}catch(t){n.send({error:t.message\|\|t}),t.stack?console.log(t.stack):console.log(t)}}}function S(t){return JSON.parse(JSON.stringify(t))}function A(t,e){if("categorical"==t.type)return{};if("survival"==t.type)return{};if("integer"==t.type\|\|"float"==t.type)return t.bins.default;if("condition"==t.type)return{mode:e.mode,breaks:e.breaks,bar_by_grade:e.bar_by_grade,bar_by_children:e.bar_by_children,value_by_max_grade:e.value_by_max_grade,value_by_most_recent:e.value_by_most_recent,value_by_computable_grade:e.value_by_computable_grade};if("geneVariant"==t.type)return{};throw"unknown term type"}},2974:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getData:()=>f,getSampleData_dictionaryTerms_termdb:()=>d,mayInitiateMatrixplots:()=>h});const r=n(1017),{get_samples:o,get_term_cte:i,interpolateSqlValues:s}=n(2852),{getFilterCTEs:a}=n(5257),l=(n(9157),n(7147),n(7219),n(334)),c=n(3856),{getSampleData_snplstOrLocus:u}=(n(2852),n(8599));async function f(t,e,n){try{return function(t,e,n){if(!e.cohort)throw"cohort missing from ds";if(!t.terms)throw"missing 'terms' parameter";t.ds=e,t.genome=n;for(const e of t.terms)e.term.name\|\|(e.term=t.ds.cohort.termdb.q.termjsonByOneid(e.term.id)),e.q\|\|console.log("do something??");if(t.currentGeneNames&&!Array.isArray(t.currentGeneNames))throw"currentGeneNames[] is not array";t.filter0&&"string"==typeof t.filter0&&(t.filter0=JSON.parse(t.filter0))}(t,e,n),await async function(t){const[e,n]=function(t){const e=[],n=[];for(const r of t){const t=r.term.type;"snplst"==t\|\|"snplocus"==t\|\|"geneVariant"==t?n.push(r):e.push(r)}return[e,n]}(t.terms),{samples:r,refs:i}=await async function(t,e){var n,r,o,i;if(!e.length)return{samples:{},refs:{byTermId:{}}};if(null!==(n=t.ds)&&void 0!==n&&null!==(r=n.cohort)&&void 0!==r&&r.db)return await d(t,e);if(null!==(o=t.ds)&&void 0!==o&&null!==(i=o.variant2samples)&&void 0!==i&&i.get)return await async function(t,e){const n={filter0:t.filter0,filterObj:t.filter,genome:t.genome,get:"samples",twLst:e,useIntegerSampleId:!0};if(t.currentGeneNames){n.geneTwLst=[];for(const e of t.currentGeneNames)n.geneTwLst.push({term:{name:e,type:"geneVariant"}})}const r=await t.ds.variant2samples.get(n),o={},i={byTermId:{}};for(const t of r){const n={sample:t.sample_id};t.__sampleName&&(n.sampleName=t.__sampleName);for(const r of e){const e=t[r.term.id];Array.isArray(e)&&null!=e[0]&&null!=e[0]?n[r.term.id]={key:e[0],value:e[0]}:null!=e&&null!=e&&(n[r.term.id]={key:e,value:e})}o[t.sample_id]=n}return{samples:o,refs:i}}(t,e);throw"unknown method for dictionary terms"}(t,e);t.ds.getSampleIdMap&&(i.bySampleId=t.ds.getSampleIdMap(r));if(e.length&&!Object.keys(r).length)return{samples:r,refs:i};const s=await async function(t,e){if(!e.find((t=>"snplst"==t.term.type\|\|"snplocus"==t.term.type)))return;if(!t.filter)return;return new Set((await o(t.filter,t.ds)).map((t=>t.id)))}(t,n);for(const o of n)if("geneVariant"==o.term.type){const n=await t.ds.mayGetGeneVariantData(o,t);for(const[i,s]of n.entries()){var a,l;if(o.term.name in s)if(e.length\|\|i in r\|\|(r[i]={sample:i}),r[i])if(r[i][o.term.name]=s[o.term.name],null!==(a=t.ds.cohort)&&void 0!==a&&null!==(l=a.termdb)&&void 0!==l&&l.additionalSampleAttributes)for(const e of null===(c=t.ds.cohort)\|\|void 0===c\|\|null===(f=c.termdb)\|\|void 0===f?void 0:f.additionalSampleAttributes){var c,f;e in s&&(r[i][e]=s[e])}}}else{if("snplst"!=o.term.type&&"snplocus"!=o.term.type)throw"unknown type of non-dictionary term";{o.type=o.term.type;const t=new Map;await u(o,t,!0);for(const[e,n]of t){if(s&&!s.has(e))continue;e in r\|\|(r[e]={sample:e});const t={};for(const[e,r]of n.id2value)t[e]=r.value;r[e][o.term.id]=t}}}return{samples:r,refs:i}}(t)}catch(t){return t.stack&&console.log(t.stack),{error:t.message\|\|t}}}async function d(t,e){const n={},r={byTermId:{}},o={},s=await a(t.filter,t.ds),l=s?s.values.slice():[],c=await Promise.all(e.map((async(e,n)=>{const a=await i(t,l,n,s,e);if(a.bins&&(r.byTermId[e.term.id]={bins:a.bins}),a.events&&(r.byTermId[e.term.id]={events:a.events}),e.term.values){const t=Object.values(e.term.values);t.find((t=>"order"in t))&&(r.byTermId[e.term.id]={keyOrder:t.sort(((t,e)=>t.order-e.order)).map((t=>t.key))})}return"id"in e.term&&(o[e.term.id]=e),a}))).catch(console.error);l.push(...e.map((t=>t.term.id\|\|t.term.name)));const u=`WITH\n\t\t${s?s.filters+",":""}\n\t\t${c.map((t=>t.sql)).join(",\n")}\n\t\t${c.map((t=>`\n\t\t\tSELECT sample, key, value, ? as term_id\n\t\t\tFROM ${t.tablename}\n\t\t\t${s?`WHERE sample IN ${s.CTEname}`:""}\n\t\t\t`)).join("UNION ALL")}`,f=t.ds.cohort.db.connection.prepare(u).all(l),d=await async function(t){if(!t.currentGeneNames)return;const e=new Set;for(const n of t.currentGeneNames){const r={term:{name:n,type:"geneVariant"}},o=await t.ds.mayGetGeneVariantData(r,t);for(const[t,n]of o.entries())e.add(t)}return e}(t);for(const{sample:t,term_id:e,key:r,value:i}of f){if(d&&!d.has(t))continue;n[t]\|\|(n[t]={sample:t});o[e];n[t][e]={key:r,value:i}}return{samples:n,refs:r}}async function h(t){if(t.cohort.matrixplots){if(!Array.isArray(t.cohort.matrixplots.plots))throw"cohort.matrixplots.plots is not array";for(const e of t.cohort.matrixplots.plots){if(!e.name)throw".name missing 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h=d.has(i.genotype_types.het)?d.get(i.genotype_types.het).size:0,p=d.has(i.genotype_types.href)?d.get(i.genotype_types.href).size:0,m=d.has(i.genotype_types.halt)?d.get(i.genotype_types.halt).size:0,g=function(t,e,n,r,o,i){const s=[];let a;if(e.cohort.termdb.selectCohort&&t){const e=t.lst.find((t=>"cohortFilter"==t.tag));e&&(a=e.tvs.values.map((t=>t.key)).sort().join(","))}for(const t of e.cohort.termdb.q.getcategory2vcfsample()){if(a&&t.subcohort!=a)continue;const c=l.copy_term(e.cohort.termdb.q.termjsonByOneid(t.term_id));for(const e of t.categories){const[a,l,u]=_(n,e.group1lst);let f,d,h;e.group2lst?[f,d,h]=_(n,e.group2lst):(f=r-a,d=i-l,h=o-u),a+f+l+d+u+h!=0&&s.push({term:c,group_name:t.group_name,parent_name:t.parent_name,group1label:e.group1label,group2label:e.group2label,table:[u,h,a,f,l,d]})}}return s}(t.filter,n,c,h,p,m);r.testcount=g.length;{const t=[];for(let e=0;e<g.length;e++)t.push(e+"\t"+g[e].table.join("\t"));const e=await f(o.join(u.binpath,"utils/fisher.2x3.R"),t);let n=0;for(const t of e)g[n++].pvalue=Number(t.split("\t")[7])}r.maxlogp=function(t){let e=0;for(const n of t)0==n.pvalue?n.logp=100:n.logp=-Math.log10(n.pvalue),e=Math.max(e,n.logp);return e}(g);const y=function(t){const e=new Map;for(const n of t)e.has(n.group_name)\|\|e.set(n.group_name,[]),e.get(n.group_name).push(n);const n=[];for(const[t,r]of e)n.push({group_name:t,categories:r});return n}(g);r.tmpfile=await function(t){const e=[];for(const n of t)for(const t of n.categories)e.push(n.group_name+"\t"+t.logp+"\t"+t.pvalue+"\t"+JSON.stringify(t));return i.write_tmpfile(e.join("\n"))}(y),b(y,r,t);{const t=.05;r.hoverdots=g.filter((e=>e.pvalue<=t))}e.send(r)}async function h(t){if(!t.cohort)throw"ds.cohort missing";if(!t.cohort.termdb)throw"cohort.termdb missing";if(!t.cohort.termdb.phewas)throw"not allowed on this dataset";t.cohort.termdb.selectCohort?await async function(t){const e=await async function(t){if(!t.cohort.termdb.phewas.precompute_subcohort2totalsamples)return;for(const e in t.cohort.termdb.phewas.precompute_subcohort2totalsamples){const n=t.cohort.termdb.phewas.precompute_subcohort2totalsamples[e];if(n.termtype)for(const e in n.termtype)n.termtype[e].samples=await s.get_samples(n.termtype[e].filter,t)}return t.cohort.termdb.phewas.precompute_subcohort2totalsamples}(t),n=function(t){const e=new Map,n=t.cohort.db.connection.prepare("SELECT FROM subcohort_terms");for(const{term_id:t,cohort:r}of n.all())e.has(t)\|\|e.set(t,new Set),e.get(t).add(r);return e}(t),o=r.createWriteStream("category2vcfsample"),i=[];for(const{group_name:r,term:a}of t.cohort.termdb.q.getAlltermsbyorder()){if(!a.type)continue;if(!n.has(a.id)){i.push(a.id);continue}let l="";{const e=t.cohort.termdb.q.getTermParent(a.id);e&&(l=e.name)}const c=m(a,t,n);for(const n of c){const i=await s.get_rows(n);let c;if("categorical"==a.type\|\|"integer"==a.type\|\|"float"==a.type)c=g(i.lst,a,t);else{if("condition"!=a.type)throw"unknown term type";c=t.cohort.termdb.phewas.comparison_groups?y(i.lst,t):g(i.lst,a,t)}c=p({categories:c,q:n,subcohortTermtype2samples:e,term:a});for(const t of c)console.log(t.group1lst.length+(t.group2lst?"/"+t.group2lst.length:"")+"\t"+t.group1label+"\t"+a.name+"\t"+n.cohortname);o.write(n.cohortname+"\t"+r+"\t"+a.id+"\t"+l+"\t"+(n.term1_q?JSON.stringify(n.term1_q):"{}")+"\t"+JSON.stringify(c)+"\n")}}o.end((()=>{console.log('Phewas precompute result written to file "category2vcfsample".'),i.length&&(console.log(i.length+" empty terms:"),console.log(i.join("\n")))}))}(t):await async function(t){const[e]=await async function(t){let e=null;if(t.cohort.termdb.phewas.samplefilter4termtype&&t.cohort.termdb.phewas.samplefilter4termtype.condition){const n=await s.get_samples(t.cohort.termdb.phewas.samplefilter4termtype.condition.filter,t);if(t.track&&t.track.vcf&&t.track.vcf.sample2arrayidx){e=[];for(const r of n)t.track.vcf.sample2arrayidx.has(r)&&e.push(r)}else 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s){if(A(t,a,n),"snplst"!=t.type&&"snplocus"!=t.type)throw"unknown type of independent non-dictionary term";await M(t,a)}return[...a.values()]}(t,[t.outcome,...t.independent],e);y=(new Date).getTime(),v.NodeJS.getSampleData=(y-g)/1e3+" sec",g=(new Date).getTime();const r=function(t,e){const n={id:t.outcome.id,name:t.outcome.term.name,rtype:"numeric"};"logistic"==t.regressionType&&(n.categories={ref:t.outcome.refGrp,nonref:k(t.outcome)});"cox"==t.regressionType&&(n.timeToEvent={timeId:t.outcome.id+"_time",eventId:t.outcome.id+"_event",timeScale:t.outcome.q.timeScale},"age"==n.timeToEvent.timeScale&&(n.timeToEvent.agestartId=t.outcome.id+"_agestart",n.timeToEvent.ageendId=t.outcome.id+"_ageend"));const r=[];for(const e of t.independent)"snplst"==e.type\|\|"snplocus"==e.type?x(e,r,t):w(e,r,t);const o=[];for(const i of e){const{sample:e,id2value:s}=i;if(!s.has(t.outcome.id)){i.noOutcome=!0;continue}const a=s.get(t.outcome.id);let l=!1;for(const e of t.independent)if("snplocus"!=e.type)if("snplst"==e.type){for(const t of e.highAFsnps.keys())if(!s.get(t)){l=!0;break}}else{if(!s.get(e.id)){l=!0;break}}if(l)continue;const c={};if("linear"==t.regressionType&&(c[n.id]=a.value),"logistic"==t.regressionType&&(c[n.id]=a.key===t.outcome.refGrp?0:1),"cox"==t.regressionType){c[n.timeToEvent.eventId]=a.key;const{age_start:e,age_end:r}=a.value;c[n.timeToEvent.timeId]=r-e,"age"==t.outcome.q.timeScale&&(c[n.timeToEvent.agestartId]=e,c[n.timeToEvent.ageendId]=r)}for(const t of r){const e=s.get(t.id);c[t.id]=e?"numeric"===t.rtype?e.value:e.key:null}o.push(c)}const i={regressionType:t.regressionType,binpath:c.binpath,data:o,outcome:n,independent:r};return i}(t,n);y=(new Date).getTime(),v.NodeJS.makeRinput=(y-g)/1e3+" sec",function(t){const e=t.regressionType,n=t.outcome;if(t.data.length<m)throw"too few samples to fit model";let r=t.independent.length;if("cox"==e)if("time"==n.timeToEvent.timeScale)r+=2;else{if("age"!=n.timeToEvent.timeScale)throw"unknown cox regression time scale";r+=4}else r+=1;if(t.data.find((t=>Object.keys(t).length!=r)))throw"unequal number of variables in data entries";if("logistic"==e){if([...new Set(t.data.map((t=>t[n.id])))].find((t=>![0,1].includes(t))))throw"non-0/1 outcome values found"}if("cox"==e){if([...new Set(t.data.map((t=>t[n.timeToEvent.eventId])))].find((t=>![0,1].includes(t))))throw"non-0/1 outcome event values found"}for(const e of t.independent)if("numeric"==e.rtype){if(e.refGrp)throw`reference group given for '${e.id}'`}else{if("factor"!=e.rtype)throw`variable rtype='${e.rtype}' not recognized`;{if(!e.refGrp)throw`reference group not given for '${e.id}'`;if("snplst"==e.type\|\|"snplocus"==e.type)continue;const n=new Set(t.data.map((t=>t[e.id])));if(n.size<2)throw`fewer than 2 categories in data of variable='${e.id}'`;if(!n.has(e.refGrp))throw`reference group missing in data of variable='${e.id}'`}}}(r);const[s,a]=function(t){const e={},n={};if(e.outcome=t.outcome.id,n[t.outcome.id]="outcome",t.outcome.timeToEvent){const r=t.outcome.timeToEvent;e.outcome_time=r.timeId,n[r.timeId]="outcome_time",e.outcome_event=r.eventId,n[r.eventId]="outcome_event","age"==r.timeScale&&(e.outcome_agestart=r.agestartId,e.outcome_ageend=r.ageendId,n[r.agestartId]="outcome_agestart",n[r.ageendId]="outcome_ageend")}for(const[r,o]of t.independent.entries())e["id"+r+"_"]=o.id,n[o.id]="id"+r+"_";if(t.outcome.id=n[t.outcome.id],t.outcome.timeToEvent){const e=t.outcome.timeToEvent;e.timeId=n[e.timeId],e.eventId=n[e.eventId],"age"==e.timeScale&&(e.agestartId=n[e.agestartId],e.ageendId=n[e.ageendId])}for(const e of t.independent)if(e.id=n[e.id],e.interactions&&e.interactions.length>0)for(const[t,r]of e.interactions.entries())e.interactions[t]=n[r];for(const e of t.data)for(const t in e)e[n[t]]=e[t],delete e[t];return[e,n]}(r),l={resultLst:[]};return await Promise.all([q(r,s,t,l),N(t,n,r,l)]),console.log("benchmark:",v),l}catch(t){return t.stack&&console.log(t.stack),{error:t.message\|\|t}}}function _(t,e,n){if(!t.q.restrictAncestry)return;if(!("name"in t.q.restrictAncestry))throw".name missing from tw.q.restrictAncestry";if(!n.cohort.termdb.restrictAncestries)throw"ds.cohort.termdb.restrictAncestries missing";const r=n.cohort.termdb.restrictAncestries.find((e=>e.name==t.q.restrictAncestry.name));if(!r)throw"unknown ancestry for restriction: "+t.q.restrictAncestry.name;if(r.pcs)t.q.restrictAncestry.pcs=r.pcs;else{if(!r.PCfileBySubcohort)throw"unknown way of accessing pcs from ds.cohort.termdb.restrictAncestries: "+t.q.restrictAncestry.name;{if(!e.filter)throw"q.filter missing while trying to access subcohort for PCfileBySubcohort";const n=C(e.filter,"cohortFilter");if(!n)throw"tvs by tag=cohortFilter missing from q.filter.lst[] while trying to access subcohort for PCfileBySubcohort";const o=n.tvs.values.map((t=>t.key)).sort().join(","),i=r.PCfileBySubcohort[o];if(!i)throw"unknown key for PCfileBySubcohort: "+o;if(!i.pcs)throw"pcs Map() missing from PCfileBySubcohort[]: "+o;t.q.restrictAncestry.pcs=i.pcs}}}function w(t,e,n){const o={id:t.id,name:t.term.name,type:"spline"==t.q.mode?"spline":"other",rtype:"continuous"==t.q.mode\|\|"spline"==t.q.mode?"numeric":"factor"};if(t.interactions.length>0){o.interactions=[];for(const e of t.interactions){const t=n.independent.find((t=>t.id==e));if("snplst"==t.type)for(const e of t.highAFsnps.keys())o.interactions.push(e);else{if("snplocus"==t.type)continue;o.interactions.push(e)}}}"factor"===o.rtype&&(o.refGrp=t.refGrp),"spline"==t.q.mode&&(o.spline={knots:t.q.knots.map((t=>Number(t.value)))},n.independent.find((t=>"snplocus"==t.type))\|\|(o.spline.plotfile=r.join(c.cachedir,Math.random().toString()+".png"))),e.push(o)}function x(t,e,n){for(const r of t.highAFsnps.keys()){const o={id:r,name:r,type:t.type};3==t.q.geneticModel?(o.rtype="factor",o.refGrp=t.q.snp2refGrp[r]):o.rtype="numeric";for(const e of n.independent)e.interactions.includes(t.id)&&(o.interactions\|\|(o.interactions=[]),o.interactions.push(e.id));e.push(o)}if(t.q.restrictAncestry)for(const n of t.q.restrictAncestry.pcs.keys())e.push({id:n,name:n,type:"float",rtype:"numeric"})}function k(t){if("condition"==t.term.type){for(const e of t.q.groups)if(e.name!=t.refGrp)return e;throw"nonref group not found for logistic outcome"}if("predefined-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!Number.isInteger(t.q.groupsetting.predefined_groupset_idx))throw'outcome.q.predefined_groupset_idx not integer when q.type is "predefined-groupset"';if(!t.term.groupsetting)throw"outcome.term.groupsetting missing";const e=t.term.groupsetting.lst[t.q.groupsetting.predefined_groupset_idx];if(!e)throw"groupset not found by 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e={},[r,o]=t.shift().split(":");e.term1=n[r],e.term2=n[o],e.lst=t,i.data.type3.interactions.push(e)}else{const e=n[t.shift()];i.data.type3.terms[e]\|\|(i.data.type3.terms[e]=t)}if(i.data.type3.label="Type III statistics",s.totalSnpEffect){if(1!=s.totalSnpEffect.rows.length)throw"total SNP effect table should have 1 row";i.data.totalSnpEffect={header:s.totalSnpEffect.header.slice(0,4)};const t=s.totalSnpEffect.rows[0].slice(0,4),e=s.totalSnpEffect.rows[0][4].split(";"),r=e.findIndex((t=>!t.includes(":"))),o=e.splice(r,1)[0];i.data.totalSnpEffect.snp=n[o];const a=[];for(const t of e){if(!t.includes(":"))throw"expected interaction";const[e,r]=t.split(":");a.push({term1:n[e],term2:n[r]})}i.data.totalSnpEffect.interactions=a,i.data.totalSnpEffect.lst=t,i.data.totalSnpEffect.label="Total SNP effect"}s.tests&&(i.data.tests=s.tests,i.data.tests.label="Statistical tests"),i.data.other=s.other,i.data.other.label="Other summary statistics";for(const e of 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i={time:e.outcome_time,event:e.outcome_event},l=s.samples.get(r);if(!l)continue;const[c,u]=l.split("/");i.series=s.effAle==c\|\|s.effAle==u?"1":"2",t.push(i)}new Set(t.map((t=>t.series))).size<2?i.add(r):o.data[r]=t}const s=await d(o);let a;for(const[e,n]of t.lowAFsnps){if(i.has(e)){a={pvalue:"NA",msg:"Cannot perform cumulative incidence test on this snp - at least one allele is not found in any sample"}}else{var l;if(1==!(null!==(l=s[e].tests)&&void 0!==l&&l.length))throw"must have a single test";const t=Number(s[e].tests[0].pvalue);if(!Number.isFinite(t))throw"invalid pvalue";a={pvalue:Number(t.toFixed(4)),ci_data:{[e]:s[e]}}}const n={id:e,AFstr:t.snpid2AFstr.get(e),data:{headerRow:S(e,t),cuminc:a}};r.resultLst.push(n)}}(i,e,n,o)}y=(new Date).getTime(),v.NodeJS.snplocusPostprocess=(y-g)/1e3+" sec"}}function S(t,e){const n=e.snpgt2count.get(t);if(!n)return{k:"Error",v:"Variant not found"};if(e.monomorphicLst.includes(t)){const[t,e]=[...n][0];return{k:"Genotype",v:t+"="+e}}const r=[`${0==e.q.alleleType?"Minor":"Alternative"} allele=${e.highAFsnps.has(t)?e.highAFsnps.get(t).effAle:e.lowAFsnps.get(t).effAle}`,"AF="+e.snpid2AFstr.get(t)];for(const[t,e]of n)r.push(t+"="+e);return{k:"Variant:",v:r.join("   ")}}function A(t,e,n){if(t.q.restrictAncestry)for(const[n,r]of t.q.restrictAncestry.pcs)for(const[t,o]of r)e.has(t)&&e.get(t).id2value.set(n,{key:o,value:o})}async function M(t,e,n){const o=(await u.read_file(r.join(c.cache_snpgt.dir,t.q.cacheid))).split("\n"),i=o[0].split("\t").slice(c.cache_snpgt.sampleColumn).map(Number);if(n)for(const t of i)e.set(t,{id2value:new Map});const s=i.map((t=>e.has(t))),a=new Map;for(let e=1;e<o.length;e++){const n=o[e].split("\t"),r=n[0],l={refAle:n[3],altAles:n[4].split(","),samples:new Map};t.q.snp2effAle?l.effAle=t.q.snp2effAle[r]:l.effAle=l.altAles[0],a.set(r,l);for(const[t,e]of i.entries()){if(!s[t])continue;const 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enabled";t.cohort.termdb.q={};const a=t.cohort.termdb.q;if(r.has("buildDate")&&(a.get_buildDate=n.prepare("select date from buildDate")),r.has("term2genes")){t.cohort.termdb.termMatch2geneSet=!0;const e=n.prepare("SELECT genes FROM term2genes WHERE id=?"),r=new Map;a.getGenesetByTermId=t=>{if(r.has(t))return r.get(t);const n=e.get(t);if(n&&n.genes){const e=JSON.parse(n.genes);return r.set(t,e),e}}}if(r.has("sampleidmap")){const e=new Map,r=new Map,o=n.prepare("SELECT FROM sampleidmap");let i=0;for(const{id:t,name:n}of o.all())e.set(t,n),r.set(n,t),i++;if(a.id2sampleName=t=>e.get(t),a.sampleName2id=t=>r.get(t),t.cohort.termdb.selectCohort){const t=n.prepare("SELECT cohort,sample_count from cohorts").all(),e={};for(const n of t)e[n.cohort]=n.sample_count;a.getcohortsamplecount=t=>t?e[t]\|\|0:i}else a.getcohortsamplecount=()=>i}if(r.has("category2vcfsample")){const t=n.prepare("SELECT * FROM category2vcfsample");let e;a.getcategory2vcfsample=()=>{if(e)return e;e=t.all();for(const t of e)t.q=JSON.parse(t.q),t.categories=JSON.parse(t.categories);return e}}if(r.has("alltermsbyorder")){const t=n.prepare("SELECT * FROM alltermsbyorder");let e;a.getAlltermsbyorder=()=>{if(e)return e;const n=t.all();e=[];for(const t of n){const n=a.termjsonByOneid(t.id);n&&e.push({group_name:t.group_name,term:n})}return e}}{const t=n.prepare("SELECT name, jsondata FROM terms WHERE id=?"),e=new Map;a.termjsonByOneid=n=>{if(e.has(n))return e.get(n);const r=t.get(n);if(r){const t=JSON.parse(r.jsondata);return t.id=n,t.name=r.name\|\|t.name,e.set(n,t),t}}}{const t=n.prepare("select id from terms where parent_id=?"),e=new Map;a.termIsLeaf=n=>{if(e.has(n))return e.get(n);let r=!0;const o=t.get(n);return o&&o.id&&(r=!1),e.set(n,r),r}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types, s.child_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE parent_id is null\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),e=new Map;a.getRootTerms=(n="")=>{const r=n;if(e.has(r))return e.get(r);const o=t.all(n).map((t=>{const e=JSON.parse(t.jsondata);return e.id=t.id,e.name=t.name\|\|e.name,e.included_types=t.included_types?t.included_types.split(","):["TO-DO-PLACEHOLDER"],e.child_types=t.child_types?t.child_types.split(","):[],e}));return e.set(r,o),o}}{const t=n.prepare("SELECT parent_id FROM terms WHERE id=?");{const e=new Map;a.termHasParent=n=>{if(e.has(n))return e.get(n);let r=!1;const o=t.get(n);return o&&o.parent_id&&(r=!0),e.set(n,r),r}}{const e=new Map;a.getTermParentId=n=>{if(e.has(n))return e.get(n);let r;const o=t.get(n);return o&&o.parent_id&&(r=o.parent_id),e.set(n,r),r}}{const t=new Map;a.getTermParent=e=>{if(t.has(e))return t.get(e);const n=a.getTermParentId(e);let r;return n&&(r=a.termjsonByOneid(n)),t.set(e,r),r}}}{const t=n.prepare("SELECT id, name, type, jsondata, s.included_types, s.child_types \n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=? 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r=n.name.toLowerCase(),o=JSON.parse(n.jsondata);o.id=n.id,o.name=n.name\|\|o.name,o.included_types=n.included_types?n.included_types.split(","):[],i&&!(0,s.CG)(o,i).has("plot")\|\|(r===e?t.equals.push(o):r.startsWith(e)?t.startsWith.push(o):r.includes(" "+e)?t.startsWord.push(o):t.includes.push(o))}return[...t.equals,...t.startsWith,...t.startsWord,...t.includes].slice(0,n)}}}{const t=n.prepare("SELECT MAX(value) AS v FROM anno_integer WHERE term_id=?"),e=n.prepare("SELECT MAX(value) AS v FROM anno_float WHERE term_id=?"),r=new Map;a.findTermMaxvalue=(n,o)=>{if(r.has(n))return r.get(n);const i=(o?t:e).get(n);return i?(r.set(n,i.v),i.v):void 0}}{const t=n.prepare("SELECT ancestor_id FROM ancestry WHERE term_id=?"),e=new Map;a.getAncestorIDs=n=>{if(e.has(n))return e.get(n);const r=t.all(n).map((t=>t.ancestor_id));return e.set(n,r),r}}{const t=n.prepare("SELECT t.name FROM ancestry as a, terms as t WHERE a.term_id=? 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l=n.queries.snvindel.byrange._tk;if(t.filter){const e=new Set((await s.get_samples(t.filter,n)).map((t=>t.id)));if(0==e.size)throw"no samples from filter";c=l.samples.map((t=>e.has(t.name)))}else c=l.samples.map((t=>!0));const u=(await i.read_file(o.join(a.cache_snpgt.dir,t.cacheid))).split("\n"),f=new Set,d=[];for(let t=1;t<u.length;t++){const e=u[t].split("\t"),n=e[0],r=e[3],o={},i={};for(let t=a.cache_snpgt.sampleColumn;t<e.length;t++){const n=e[t];if(!n)continue;if(!c[t-a.cache_snpgt.sampleColumn])continue;f.add(l.samples[t-a.cache_snpgt.sampleColumn].name),i[n]=1+(i[n]\|\|0);const r=n.split("/");for(const t of r)o[t]=1+(o[t]\|\|0)}const s=[];for(const t in o)s.push({allele:t,count:o[t],isRef:t==r});d.push({snpid:n,alleles:s,gt2count:i})}return{numOfSampleWithAnyValidGT:f.size,snps:d}}(t,0,n);if(t.snptext)return await async function(t,e,n){if(!n.snp)throw"snp not supported by genome";if(!t.snptext)throw".snptext missing";const s=function(t){const e=[];for(const n of t.trim().split("\n")){const[t,r]=n.trim().split(/[\s\t]/);if(t&&t.startsWith("rs")){if(e.find((e=>e.rsid==t)))continue;const n={rsid:t,snpid:t};r&&(n.effectAllele=r),e.push(n)}else e.push({rsid:t,snpid:t,invalid:"INVALID RSID"})}return e}(t.snptext);if(!s.length)throw"no snps";await async function(t,e){for(const n of t)if(!n.invalid)if(n.chr&&"string"==typeof n.chr){const t=e.chrlookup[n.chr.toUpperCase()];if(!t){n.invalid=!0;continue}if(!Number.isInteger(n.pos)){n.invalid=!0;continue}if(n.pos<=0\|\|n.pos>=t.len){n.invalid=!0;continue}}else if(n.rsid){const t=await i.query_bigbed_by_name(e.snp.bigbedfile,n.rsid),r=[];for(const n of t){const t=n.split("\t"),o=e.chrlookup[t[0].toUpperCase()];o&&o.major&&r.push(t)}if(0==r.length){n.invalid=!0;continue}const o=r[0];n.chr=o[0],n.pos=Number.parseInt(o[1]),n.dbsnpRef=o[4],n.dbsnpAlts=o[6].split(",").filter(Boolean)}else n.invalid=!0;if(!t.find((t=>!t.invalid)))throw"no valid variants"}(s,n);const l=await async function(t,e,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 l=new Set,u=[];for(const t of e){if(t.invalid)continue;let e;var d;if(s.chr2files){if(e=null===(d=s.chr2files)\|\|void 0===d?void 0:d[t.chr].file,!e)throw"chr not in chr2files"}else if(s.chr2bcffile){if(e=s.chr2bcffile[t.chr],!e)throw"chr not in chr2bcffile"}else e=s.file\|\|s.url;l.add(e);const n=(s.nochr?t.chr.replace("chr",""):t.chr)+"\t"+(t.pos+1);u.push(n)}const h=o.join(a.cachedir,await i.write_tmpfile(u.join("\n"))),p=o.join(a.cachedir,await i.write_tmpfile([...l].join("\n")));await i.get_lines_bigfile({isbcf:!0,args:["query","-R",h,"-f",c,"-v",p],dir:s.dir,callback:t=>{const n=t.split("\t"),r=(s.nochr?"chr":"")+n[0],o=n[1],i=n[2],a=n[3].split(","),l=e.find((t=>{if(t.chr==r&&t.pos===o-1&&t.dbsnpRef==i&&t.dbsnpAlts.some((t=>a.includes(t))))return t}));if(l){l.referenceAllele=i,l.altAlleles=a,l.gtlst=[];for(let t=4;t<n.length;t++)l.gtlst.push(n[t]==f?"":n[t])}}}),r.unlink(h,(()=>{})),r.unlink(p,(()=>{}));const m=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid\|\|t.gtlst&&(m.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele\|\|"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const g=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4Math.random());return await i.write_file(o.join(a.cache_snpgt.dir,g),m.join("\n")),g}(t,s,e);return{snps:s,cacheid:l}}(t,n,h);if(t.chr)return await async function(t,e,n){const r=Number(t.start),s=Number(t.stop);if(!Number.isInteger(r)\|\|!Number.isInteger(s))throw"start/stop are not integers";if(r>s\|\|r<0)throw"invalid start/stop coordinate";let c,h;if(e.track){if(c=e.track.vcf,!c)throw"ds.track.vcf missing";if(h=c.chr2bcffile[t.chr],!h)throw"chr not in chr2bcffile"}else{var m;if(c=e.queries.snvindel.byrange._tk,c.chr2files)h=null===(m=c.chr2files)\|\|void 0===m?void 0:m[t.chr].file;else h=c.file\|\|c.url;if(!h)throw"no bcf file"}const g=(c.nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+s,y=["query",h,"-r",g,"-f",u];t.variant_filter&&p(t.variant_filter,y);const v={snps:[]},b=["snpid\tchr\tpos\tref\talt\teff\t"+c.samples.map((t=>t.name)).join("\t")];return await i.get_lines_bigfile({isbcf:!0,args:y,dir:c.dir,callback:(e,n)=>{if(v.snps.length>=d)return n.kill(),void(v.reachedVariantLimit=!0);const r=e.split("\t"),o=Number(r[0])-1,i=r[2],s=r[3].split(","),a=o+"."+i+"."+s.join(","),u={snpid:a,chr:t.chr,pos:o};l(c,i,s,u,r[4],r[1]);for(const t of u.mlst)t.vcf_id&&(t.mname=t.vcf_id);v.snps.push(u);const h=[a,t.chr,o,i,s.join(","),""];for(let t=5;t<r.length;t++)h.push(r[t]==f?"":r[t]);b.push(h.join("\t"))}}),v.cacheid=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4Math.random()),await i.write_file(o.join(a.cache_snpgt.dir,v.cacheid),b.join("\n")),v}(t,n);throw"unknown how to validate"}catch(t){return t.stack&&console.log(t.stack),{error:t.message\|\|t}}}function p(t,e){const n=[];for(const e of t.lst)if(e.tvs.values){const t=e.tvs.isnot?"!=":"=";for(const r of e.tvs.values){const o=isNaN(r.key)?`"${r.key}"`:Number(r.key);n.push(`INFO/${e.tvs.term.id}${t}${o}`)}}else{if(!e.tvs.ranges)throw`unknown tvs spec for info_field: type=${e.type}, term.id=${e.tvs.term.id}`;for(const t of e.tvs.ranges)"start"in t&&n.push(`INFO/${e.tvs.term.id} ${t.startinclusive?">=":">"} ${t.start}`),"stop"in t&&n.push(`INFO/${e.tvs.term.id} ${t.stopinclusive?"<=":"<"} ${t.stop}`)}0!=n.length&&e.push("-i",n.join(" && "))}},2747:(t,e,n)=>{"use strict";n.r(e),n.d(e,{groupset:()=>s,values:()=>o});var r=n(2852);const o={getCTE(t,e,n,o,i){i.push(e.id);const s=(0,r.getUncomputableClause)(e,o);return i.push(...s.values),{sql:`${t} AS (\n\t\t\t\tSELECT sample,value as key, value as value\n\t\t\t\tFROM 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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 ${i}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${s.join("\nUNION ALL\n")}\n\t\t)`,tablename:t}}},2852:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getUncomputableClause:()=>v,get_bins:()=>_,get_numericMinMaxPct:()=>x,get_numericsummary:()=>w,get_rows:()=>p,get_rows_by_one_key:()=>h,get_samplecount:()=>f,get_samples:()=>u,get_summary:()=>g,get_summary_numericcategories:()=>d,get_term_cte:()=>m,interpolateSqlValues:()=>k});const r=n(9699),o=n(4048),i=n(5257).getFilterCTEs,s=n(827),a=n(2747),l=n(9723),c=n(610).s;n(334);async function u(t,e,n=!1){const r=await i(t,e),o=e.cohort.db.connection.prepare(r?`WITH ${r.filters} SELECT sample as id, name FROM ${r.CTEname} join sampleidmap on sample = sampleidmap.id`:"SELECT id, name FROM sampleidmap");let s;if(s=r?o.all(r.values):o.all(),n)return s;for(const t of s)delete t.name;return s}async function f(t,e){if(!t.filter)throw"filter missing";let n;if("object"==typeof t.filter)n=t.filter;else{if("string"!=typeof t.filter)throw"q.filter not obj or str";n=JSON.parse(t.filter)}const r=await i(n,e),o=`WITH ${r.filters}\n\t\tSELECT 'FILTERED_COHORT' as subcohort, count(distinct sample) as samplecount \n\t\tFROM ${r.CTEname}`;return e.cohort.db.connection.prepare(o).all(r.values)}async function d(t){const e=t.ds.cohort.termdb.q.termjsonByOneid(t.term_id);if("integer"!=e.type&&"float"!=e.type)throw"term is not numeric";if(!e.values)return[];const n=await i(t.filter,t.ds),r=n?n.values.slice():[];r.push(t.term_id);const o=[];for(const t in e.values)o.push("?"),r.push(Number(t));const s=`\n\t\t${n?"WITH "+n.filters:""}\n\t\tSELECT count(sample) AS samplecount,value\n\t\tFROM anno_${e.type}\n\t\tWHERE term_id=?\n\t\t${n?"AND sample IN "+n.CTEname:""}\n\t\tAND value IN (${o.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(s).all(r)}async function h(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await i(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const o=`\n\t\t${e?"WITH "+e.filters:""}\n\t\tSELECT sample, value\n\t\tFROM anno_${r.type}\n\t\tWHERE term_id=?\n\t\t${e?" AND sample IN "+e.CTEname:""}`;return t.ds.cohort.db.connection.prepare(o).all(n)}async function p(t,e={}){"string"==typeof t.filter&&(t.filter=JSON.parse(decodeURIComponent(t.filter)));const n=Object.assign({withCTEs:!0,columnas:"t1.sample AS sample",groupby:""},e),r=await i(t.filter,t.ds),o=r?r.values.slice():[],s=await m(t,o,0,r),a=await m(t,o,1,r),l=await m(t,o,2,r),c=[s,a,l].map(((t,e)=>`\n\t\tSELECT sample, key, value, ${e} as termNum\n\t\tFROM ${t.tablename}\n\t\t${r?"WHERE sample IN "+r.CTEname:""}\n\t`)).join("\nUNION ALL\n"),u=`WITH\n\t\t${r?r.filters+",":""}\n\t\t${s.sql},\n\t\t${a.sql},\n\t\t${l.sql}\n\t\t${c}`;try{const e=t.ds.cohort.db.connection.prepare(u).all(o),i=new Map;for(const t of e){i.has(t.sample)\|\|i.set(t.sample,{sample:t.sample});const e=i.get(t.sample),n=`key${t.termNum}`;n in e\|\|(e[n]=[]),e[n].push(t)}const c=[],f=new Map;for(const e of i.values())if("key1"in e){if(t.term0_q&&t.term0_id){if(!("key0"in e))continue}else e.key0=[{key:"",value:""}];if(t.term2_q&&(t.term2_id\|\|"samplelst"===t.term2.type)){if(!("key2"in e))continue}else e.key2=[{key:"",value:""}];e.rows=[];for(const t of e.key0)for(const n of e.key1)for(const r of e.key2)e.rows.push({sample:e.sample,key0:t.key,val0:t.value,key1:n.key,val1:n.value,key2:r.key,val2:r.value});for(const t of e.rows)if(n.groupby){if(!f.has(t[n.groupby])){const e=Object.assign({samplecount:0},t);c.push(e),f.set(t[n.groupby],e)}f.get(t[n.groupby]).samplecount++}else c.push(t)}return n.withCTEs?{lst:c,CTE0:s,CTE1:a,CTE2:l,filter:r}:c}catch(t){throw console.log("error in sql:\n",k(u,o)),t}}async function m(t,e,n,r,o=null){const i=o&&o.term\|\|t[`term${n}`],u=i?i.id:t["term"+n+"_id"];if("samplelst"!=(null==i?void 0:i.type))if(o\|\|1!=n){if(!u){const t="samplekey_"+n;return{tablename:t,sql:`${t} AS (\nSELECT null AS sample, '' as key, '' as value\n)`}}}else if(!u)throw"missing term1 id";const f=i&&i.type?i:t.ds.cohort.termdb.q.termjsonByOneid(u);if(!f)throw`no term 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Fr(){var t=Rr,e=Ir,n=Pr,r=960,o=500,i=20,s=2,a=3i,l=r+2a>>s,c=o+2a>>s,u=Nr(20);function f(r){var o=new Float32Array(lc),u=Math.pow(2,-s),f=-1;for(const i of r){var d=(t(i,++f,r)+a)u,h=(e(i,f,r)+a)u,p=+n(i,f,r);if(d>=0&&d<l&&h>=0&&h<c){var m=Math.floor(d),g=Math.floor(h),y=d-m-.5,v=h-g-.5;o[m+gl]+=(1-y)(1-v)p,o[m+1+gl]+=y(1-v)p,o[m+1+(g+1)l]+=yvp,o[m+(g+1)l]+=(1-y)vp}}return(0,Or.u8)({data:o,width:l,height:c},iu),o}function d(t){var e=f(t),n=u(e),r=Math.pow(2,2s);return Array.isArray(n)\|\|(n=(0,xr.ZP)(Number.MIN_VALUE,(0,Er.Z)(e)/r,n)),jr().size([l,c]).thresholds(n.map((t=>tr)))(e).map(((t,e)=>(t.value=+n[e],h(t))))}function h(t){return t.coordinates.forEach(p),t}function p(t){t.forEach(m)}function m(t){t.forEach(g)}function g(t){t[0]=t[0]Math.pow(2,s)-a,t[1]=t[1]Math.pow(2,s)-a}function y(){return l=r+2(a=3i)>>s,c=o+2a>>s,d}return d.contours=function(t){var e=f(t),n=jr().size([l,c]),r=Math.pow(2,2s),o=t=>{t=+t;var o=h(n.contour(e,tr));return o.value=t,o};return Object.defineProperty(o,"max",{get:()=>(0,Er.Z)(e)/r}),o},d.x=function(e){return arguments.length?(t="function"==typeof e?e:Nr(+e),d):t},d.y=function(t){return arguments.length?(e="function"==typeof t?t:Nr(+t),d):e},d.weight=function(t){return arguments.length?(n="function"==typeof t?t:Nr(+t),d):n},d.size=function(t){if(!arguments.length)return[r,o];var e=+t[0],n=+t[1];if(!(e>=0&&n>=0))throw new Error("invalid size");return r=e,o=n,y()},d.cellSize=function(t){if(!arguments.length)return 1<<s;if(!((t=+t)>=1))throw new Error("invalid cell size");return s=Math.floor(Math.log(t)/Math.LN2),y()},d.thresholds=function(t){return arguments.length?(u="function"==typeof t?t:Array.isArray(t)?Nr(kr.call(t)):Nr(t),d):u},d.bandwidth=function(t){if(!arguments.length)return Math.sqrt(i(i+1));if(!((t=+t)>=0))throw new Error("invalid bandwidth");return i=(Math.sqrt(4tt+1)-1)/2,y()},d}const Lr=134217729,Dr=33306690738754706e-32;function zr(t,e,n,r,o){let i,s,a,l,c=e[0],u=r[0],f=0,d=0;u>c==u>-c?(i=c,c=e[++f]):(i=u,u=r[++d]);let h=0;if(f<t&&d<n)for(u>c==u>-c?(s=c+i,a=i-(s-c),c=e[++f]):(s=u+i,a=i-(s-u),u=r[++d]),i=s,0!==a&&(o[h++]=a);f<t&&d<n;)u>c==u>-c?(s=i+c,l=s-i,a=i-(s-l)+(c-l),c=e[++f]):(s=i+u,l=s-i,a=i-(s-l)+(u-l),u=r[++d]),i=s,0!==a&&(o[h++]=a);for(;f<t;)s=i+c,l=s-i,a=i-(s-l)+(c-l),c=e[++f],i=s,0!==a&&(o[h++]=a);for(;d<n;)s=i+u,l=s-i,a=i-(s-l)+(u-l),u=r[++d],i=s,0!==a&&(o[h++]=a);return 0===i&&0!==h\|\|(o[h++]=i),h}function Br(t){return new Float64Array(t)}const $r=22204460492503146e-32,Zr=11093356479670487e-47,Gr=Br(4),Ur=Br(8),Wr=Br(12),Jr=Br(16),Hr=Br(4);function Vr(t,e,n,r,o,i){const s=(e-i)(n-o),a=(t-o)(r-i),l=s-a;if(0===s\|\|0===a\|\|s>0!=a>0)return l;const c=Math.abs(s+a);return Math.abs(l)>=33306690738754716e-32c?l:-function(t,e,n,r,o,i,s){let a,l,c,u,f,d,h,p,m,g,y,v,b,_,w,x,k,q;const N=t-o,S=n-o,A=e-i,M=r-i;_=NM,d=LrN,h=d-(d-N),p=N-h,d=LrM,m=d-(d-M),g=M-m,w=pg-(_-hm-pm-hg),x=AS,d=LrA,h=d-(d-A),p=A-h,d=LrS,m=d-(d-S),g=S-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Gr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Gr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Gr[2]=v-(q-f)+(y-f),Gr[3]=q;let T=function(t,e){let n=e[0];for(let r=1;r<t;r++)n+=e[r];return n}(4,Gr),C=$rs;if(T>=C\|\|-T>=C)return T;if(f=t-N,a=t-(N+f)+(f-o),f=n-S,c=n-(S+f)+(f-o),f=e-A,l=e-(A+f)+(f-i),f=r-M,u=r-(M+f)+(f-i),0===a&&0===l&&0===c&&0===u)return T;if(C=Zrs+DrMath.abs(T),T+=Nu+Ma-(Ac+Sl),T>=C\|\|-T>=C)return T;_=aM,d=Lra,h=d-(d-a),p=a-h,d=LrM,m=d-(d-M),g=M-m,w=pg-(_-hm-pm-hg),x=lS,d=Lrl,h=d-(d-l),p=l-h,d=LrS,m=d-(d-S),g=S-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Hr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Hr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Hr[2]=v-(q-f)+(y-f),Hr[3]=q;const j=zr(4,Gr,4,Hr,Ur);_=Nu,d=LrN,h=d-(d-N),p=N-h,d=Lru,m=d-(d-u),g=u-m,w=pg-(_-hm-pm-hg),x=Ac,d=LrA,h=d-(d-A),p=A-h,d=Lrc,m=d-(d-c),g=c-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Hr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Hr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Hr[2]=v-(q-f)+(y-f),Hr[3]=q;const O=zr(j,Ur,4,Hr,Wr);_=au,d=Lra,h=d-(d-a),p=a-h,d=Lru,m=d-(d-u),g=u-m,w=pg-(_-hm-pm-hg),x=lc,d=Lrl,h=d-(d-l),p=l-h,d=Lrc,m=d-(d-c),g=c-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Hr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Hr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Hr[2]=v-(q-f)+(y-f),Hr[3]=q;const E=zr(O,Wr,4,Hr,Jr);return Jr[E-1]}(t,e,n,r,o,i,c)}Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(8),Br(8),Br(8),Br(4),Br(8),Br(8),Br(8),Br(12);Br(192),Br(192);Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(4),Br(4),Br(4),Br(8),Br(16),Br(16),Br(16),Br(32),Br(32),Br(48),Br(64);Br(1152),Br(1152);Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(1152),Br(1152),Br(1152),Br(1152),Br(1152),Br(2304),Br(2304),Br(3456),Br(5760),Br(8),Br(8),Br(8),Br(16),Br(24),Br(48),Br(48),Br(96),Br(192),Br(384),Br(384),Br(384),Br(768);Br(96),Br(96),Br(96),Br(1152);const Yr=Math.pow(2,-52),Qr=new Uint32Array(512);class Kr{static from(t,e=oo,n=io){const r=t.length,o=new Float64Array(2r);for(let i=0;i<r;i++){const r=t[i];o[2i]=e(r),o[2i+1]=n(r)}return new Kr(o)}constructor(t){const e=t.length>>1;if(e>0&&"number"!=typeof t[0])throw new Error("Expected coords to contain numbers.");this.coords=t;const n=Math.max(2e-5,0);this._triangles=new Uint32Array(3n),this._halfedges=new Int32Array(3n),this._hashSize=Math.ceil(Math.sqrt(e)),this._hullPrev=new Uint32Array(e),this._hullNext=new Uint32Array(e),this._hullTri=new Uint32Array(e),this._hullHash=new Int32Array(this._hashSize).fill(-1),this._ids=new Uint32Array(e),this._dists=new Float64Array(e),this.update()}update(){const{coords:t,_hullPrev:e,_hullNext:n,_hullTri:r,_hullHash:o}=this,i=t.length>>1;let s=1/0,a=1/0,l=-1/0,c=-1/0;for(let e=0;e<i;e++){const n=t[2e],r=t[2e+1];n<s&&(s=n),r<a&&(a=r),n>l&&(l=n),r>c&&(c=r),this._ids[e]=e}const u=(s+l)/2,f=(a+c)/2;let d,h,p,m=1/0;for(let e=0;e<i;e++){const n=Xr(u,f,t[2e],t[2e+1]);n<m&&(d=e,m=n)}const g=t[2d],y=t[2d+1];m=1/0;for(let e=0;e<i;e++){if(e===d)continue;const n=Xr(g,y,t[2e],t[2e+1]);n<m&&n>0&&(h=e,m=n)}let v=t[2h],b=t[2h+1],_=1/0;for(let e=0;e<i;e++){if(e===d\|\|e===h)continue;const n=eo(g,y,v,b,t[2e],t[2e+1]);n<_&&(p=e,_=n)}let w=t[2p],x=t[2p+1];if(_===1/0){for(let e=0;e<i;e++)this._dists[e]=t[2e]-t[0]\|\|t[2e+1]-t[1];no(this._ids,this._dists,0,i-1);const e=new Uint32Array(i);let n=0;for(let t=0,r=-1/0;t<i;t++){const o=this._ids[t];this._dists[o]>r&&(e[n++]=o,r=this._dists[o])}return this.hull=e.subarray(0,n),this.triangles=new Uint32Array(0),void(this.halfedges=new Uint32Array(0))}if(Vr(g,y,v,b,w,x)<0){const t=h,e=v,n=b;h=p,v=w,b=x,p=t,w=e,x=n}const k=function(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=ss+aa,f=ll+cc,d=.5/(sc-al),h=t+(cu-af)d,p=e+(sf-lu)d;return{x:h,y:p}}(g,y,v,b,w,x);this._cx=k.x,this._cy=k.y;for(let e=0;e<i;e++)this._dists[e]=Xr(t[2e],t[2e+1],k.x,k.y);no(this._ids,this._dists,0,i-1),this._hullStart=d;let q=3;n[d]=e[p]=h,n[h]=e[d]=p,n[p]=e[h]=d,r[d]=0,r[h]=1,r[p]=2,o.fill(-1),o[this._hashKey(g,y)]=d,o[this._hashKey(v,b)]=h,o[this._hashKey(w,x)]=p,this.trianglesLen=0,this._addTriangle(d,h,p,-1,-1,-1);for(let i,s,a=0;a<this._ids.length;a++){const l=this._ids[a],c=t[2l],u=t[2l+1];if(a>0&&Math.abs(c-i)<=Yr&&Math.abs(u-s)<=Yr)continue;if(i=c,s=u,l===d\|\|l===h\|\|l===p)continue;let f=0;for(let t=0,e=this._hashKey(c,u);t<this._hashSize&&(f=o[(e+t)%this._hashSize],-1===f\|\|f===n[f]);t++);f=e[f];let m,g=f;for(;m=n[g],Vr(c,u,t[2g],t[2g+1],t[2m],t[2m+1])>=0;)if(g=m,g===f){g=-1;break}if(-1===g)continue;let y=this._addTriangle(g,l,n[g],-1,-1,r[g]);r[l]=this._legalize(y+2),r[g]=y,q++;let v=n[g];for(;m=n[v],Vr(c,u,t[2v],t[2v+1],t[2m],t[2m+1])<0;)y=this._addTriangle(v,l,m,r[l],-1,r[v]),r[l]=this._legalize(y+2),n[v]=v,q--,v=m;if(g===f)for(;m=e[g],Vr(c,u,t[2m],t[2m+1],t[2g],t[2g+1])<0;)y=this._addTriangle(m,l,g,-1,r[g],r[m]),this._legalize(y+2),r[m]=y,n[g]=g,q--,g=m;this._hullStart=e[l]=g,n[g]=e[v]=l,n[l]=v,o[this._hashKey(c,u)]=l,o[this._hashKey(t[2g],t[2g+1])]=g}this.hull=new Uint32Array(q);for(let t=0,e=this._hullStart;t<q;t++)this.hull[t]=e,e=n[e];this.triangles=this._triangles.subarray(0,this.trianglesLen),this.halfedges=this._halfedges.subarray(0,this.trianglesLen)}_hashKey(t,e){return Math.floor(function(t,e){const n=t/(Math.abs(t)+Math.abs(e));return(e>0?3-n:1+n)/4}(t-this._cx,e-this._cy)this._hashSize)%this._hashSize}_legalize(t){const{_triangles:e,_halfedges:n,coords:r}=this;let o=0,i=0;for(;;){const s=n[t],a=t-t%3;if(i=a+(t+2)%3,-1===s){if(0===o)break;t=Qr[--o];continue}const l=s-s%3,c=a+(t+1)%3,u=l+(s+2)%3,f=e[i],d=e[t],h=e[c],p=e[u];if(to(r[2f],r[2f+1],r[2d],r[2d+1],r[2h],r[2h+1],r[2p],r[2p+1])){e[t]=p,e[s]=f;const r=n[u];if(-1===r){let e=this._hullStart;do{if(this._hullTri[e]===u){this._hullTri[e]=t;break}e=this._hullPrev[e]}while(e!==this._hullStart)}this._link(t,r),this._link(s,n[i]),this._link(i,u);const a=l+(s+1)%3;o<Qr.length&&(Qr[o++]=a)}else{if(0===o)break;t=Qr[--o]}}return i}_link(t,e){this._halfedges[t]=e,-1!==e&&(this._halfedges[e]=t)}_addTriangle(t,e,n,r,o,i){const s=this.trianglesLen;return this._triangles[s]=t,this._triangles[s+1]=e,this._triangles[s+2]=n,this._link(s,r),this._link(s+1,o),this._link(s+2,i),this.trianglesLen+=3,s}}function Xr(t,e,n,r){const o=t-n,i=e-r;return oo+ii}function to(t,e,n,r,o,i,s,a){const l=t-s,c=e-a,u=n-s,f=r-a,d=o-s,h=i-a,p=uu+ff,m=dd+hh;return l(fm-ph)-c(um-pd)+(ll+cc)(uh-fd)<0}function eo(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=ss+aa,f=ll+cc,d=.5/(sc-al),h=(cu-af)d,p=(sf-lu)d;return hh+pp}function no(t,e,n,r){if(r-n<=20)for(let o=n+1;o<=r;o++){const r=t[o],i=e[r];let s=o-1;for(;s>=n&&e[t[s]]>i;)t[s+1]=t[s--];t[s+1]=r}else{let o=n+1,i=r;ro(t,n+r>>1,o),e[t[n]]>e[t[r]]&&ro(t,n,r),e[t[o]]>e[t[r]]&&ro(t,o,r),e[t[n]]>e[t[o]]&&ro(t,n,o);const s=t[o],a=e[s];for(;;){do{o++}while(e[t[o]]<a);do{i--}while(e[t[i]]>a);if(i<o)break;ro(t,o,i)}t[n+1]=t[i],t[i]=s,r-o+1>=i-n?(no(t,e,o,r),no(t,e,n,i-1)):(no(t,e,n,i-1),no(t,e,o,r))}}function ro(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function oo(t){return t[0]}function io(t){return t[1]}const so=1e-6;class ao{constructor(){this._x0=this._y0=this._x1=this._y1=null,this._=""}moveTo(t,e){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}`}closePath(){null!==this._x1&&(this._x1=this._x0,this._y1=this._y0,this._+="Z")}lineTo(t,e){this._+=`L${this._x1=+t},${this._y1=+e}`}arc(t,e,n){const r=(t=+t)+(n=+n),o=e=+e;if(n<0)throw new Error("negative radius");null===this._x1?this._+=`M${r},${o}`:(Math.abs(this._x1-r)>so\|\|Math.abs(this._y1-o)>so)&&(this._+="L"+r+","+o),n&&(this._+=`A${n},${n},0,1,1,${t-n},${e}A${n},${n},0,1,1,${this._x1=r},${this._y1=o}`)}rect(t,e,n,r){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}h${+n}v${+r}h${-n}Z`}value(){return this._\|\|null}}class lo{constructor(){this._=[]}moveTo(t,e){this._.push([t,e])}closePath(){this._.push(this._[0].slice())}lineTo(t,e){this._.push([t,e])}value(){return this._.length?this._:null}}class co{constructor(t,[e,n,r,o]=[0,0,960,500]){if(!((r=+r)>=(e=+e)&&(o=+o)>=(n=+n)))throw new Error("invalid bounds");this.delaunay=t,this._circumcenters=new Float64Array(2t.points.length),this.vectors=new Float64Array(2t.points.length),this.xmax=r,this.xmin=e,this.ymax=o,this.ymin=n,this._init()}update(){return this.delaunay.update(),this._init(),this}_init(){const{delaunay:{points:t,hull:e,triangles:n},vectors:r}=this,o=this.circumcenters=this._circumcenters.subarray(0,n.length/32);for(let e,r,i=0,s=0,a=n.length;i<a;i+=3,s+=2){const a=2n[i],l=2n[i+1],c=2n[i+2],u=t[a],f=t[a+1],d=t[l],h=t[l+1],p=t[c],m=t[c+1],g=d-u,y=h-f,v=p-u,b=m-f,_=2(gb-yv);if(Math.abs(_)<1e-9){let o=1e9;const i=2n[0];o=Math.sign((t[i]-u)b-(t[i+1]-f)v),e=(u+p)/2-ob,r=(f+m)/2+ov}else{const t=1/_,n=gg+yy,o=vv+bb;e=u+(bn-yo)t,r=f+(go-vn)t}o[s]=e,o[s+1]=r}let i,s,a,l=e[e.length-1],c=4l,u=t[2l],f=t[2l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],i=c,s=u,a=f,c=4l,u=t[2l],f=t[2l+1],r[i+2]=r[c]=a-f,r[i+3]=r[c+1]=u-s}render(t){const e=null==t?t=new ao:void 0,{delaunay:{halfedges:n,inedges:r,hull:o},circumcenters:i,vectors:s}=this;if(o.length<=1)return null;for(let e=0,r=n.length;e<r;++e){const r=n[e];if(r<e)continue;const o=2Math.floor(e/3),s=2Math.floor(r/3),a=i[o],l=i[o+1],c=i[s],u=i[s+1];this._renderSegment(a,l,c,u,t)}let a,l=o[o.length-1];for(let e=0;e<o.length;++e){a=l,l=o[e];const n=2Math.floor(r[l]/3),c=i[n],u=i[n+1],f=4a,d=this._project(c,u,s[f+2],s[f+3]);d&&this._renderSegment(c,u,d[0],d[1],t)}return e&&e.value()}renderBounds(t){const e=null==t?t=new ao:void 0;return t.rect(this.xmin,this.ymin,this.xmax-this.xmin,this.ymax-this.ymin),e&&e.value()}renderCell(t,e){const n=null==e?e=new ao:void 0,r=this._clip(t);if(null===r\|\|!r.length)return;e.moveTo(r[0],r[1]);let o=r.length;for(;r[0]===r[o-2]&&r[1]===r[o-1]&&o>1;)o-=2;for(let t=2;t<o;t+=2)r[t]===r[t-2]&&r[t+1]===r[t-1]\|\|e.lineTo(r[t],r[t+1]);return e.closePath(),n&&n.value()}cellPolygons(){const{delaunay:{points:t}}=this;for(let e=0,n=t.length/2;e<n;++e){const t=this.cellPolygon(e);t&&(t.index=e,yield t)}}cellPolygon(t){const e=new lo;return this.renderCell(t,e),e.value()}_renderSegment(t,e,n,r,o){let i;const s=this._regioncode(t,e),a=this._regioncode(n,r);0===s&&0===a?(o.moveTo(t,e),o.lineTo(n,r)):(i=this._clipSegment(t,e,n,r,s,a))&&(o.moveTo(i[0],i[1]),o.lineTo(i[2],i[3]))}contains(t,e,n){return(e=+e)==e&&(n=+n)==n&&this.delaunay._step(t,e,n)===t}neighbors(t){const e=this._clip(t);if(e)for(const n of this.delaunay.neighbors(t)){const t=this._clip(n);if(t)t:for(let r=0,o=e.length;r<o;r+=2)for(let i=0,s=t.length;i<s;i+=2)if(e[r]==t[i]&&e[r+1]==t[i+1]&&e[(r+2)%o]==t[(i+s-2)%s]&&e[(r+3)%o]==t[(i+s-1)%s]){yield n;break t}}}_cell(t){const{circumcenters:e,delaunay:{inedges:n,halfedges:r,triangles:o}}=this,i=n[t];if(-1===i)return null;const s=[];let a=i;do{const n=Math.floor(a/3);if(s.push(e[2n],e[2n+1]),a=a%3==2?a-2:a+1,o[a]!==t)break;a=r[a]}while(a!==i&&-1!==a);return s}_clip(t){if(0===t&&1===this.delaunay.hull.length)return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];const e=this._cell(t);if(null===e)return null;const{vectors:n}=this,r=4t;return n[r]\|\|n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,o,i,s,a=null,l=e[n-2],c=e[n-1],u=this._regioncode(l,c),f=0;for(let d=0;d<n;d+=2)if(r=l,o=c,l=e[d],c=e[d+1],i=u,u=this._regioncode(l,c),0===i&&0===u)s=f,f=0,a?a.push(l,c):a=[l,c];else{let e,n,d,h,p;if(0===i){if(null===(e=this._clipSegment(r,o,l,c,i,u)))continue;[n,d,h,p]=e}else{if(null===(e=this._clipSegment(l,c,r,o,u,i)))continue;[h,p,n,d]=e,s=f,f=this._edgecode(n,d),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(n,d):a=[n,d]}s=f,f=this._edgecode(h,p),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(h,p):a=[h,p]}if(a)s=f,f=this._edgecode(a[0],a[1]),s&&f&&this._edge(t,s,f,a,a.length);else if(this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2))return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];return a}_clipSegment(t,e,n,r,o,i){for(;;){if(0===o&&0===i)return[t,e,n,r];if(o&i)return null;let s,a,l=o\|\|i;8&l?(s=t+(n-t)(this.ymax-e)/(r-e),a=this.ymax):4&l?(s=t+(n-t)(this.ymin-e)/(r-e),a=this.ymin):2&l?(a=e+(r-e)(this.xmax-t)/(n-t),s=this.xmax):(a=e+(r-e)(this.xmin-t)/(n-t),s=this.xmin),o?(t=s,e=a,o=this._regioncode(t,e)):(n=s,r=a,i=this._regioncode(n,r))}}_clipInfinite(t,e,n,r,o,i){let s,a=Array.from(e);if((s=this._project(a[0],a[1],n,r))&&a.unshift(s[0],s[1]),(s=this._project(a[a.length-2],a[a.length-1],o,i))&&a.push(s[0],s[1]),a=this._clipFinite(t,a))for(let e,n=0,r=a.length,o=this._edgecode(a[r-2],a[r-1]);n<r;n+=2)e=o,o=this._edgecode(a[n],a[n+1]),e&&o&&(n=this._edge(t,e,o,a,n),r=a.length);else this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2)&&(a=[this.xmin,this.ymin,this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax]);return a}_edge(t,e,n,r,o){for(;e!==n;){let n,i;switch(e){case 5:e=4;continue;case 4:e=6,n=this.xmax,i=this.ymin;break;case 6:e=2;continue;case 2:e=10,n=this.xmax,i=this.ymax;break;case 10:e=8;continue;case 8:e=9,n=this.xmin,i=this.ymax;break;case 9:e=1;continue;case 1:e=5,n=this.xmin,i=this.ymin}r[o]===n&&r[o+1]===i\|\|!this.contains(t,n,i)\|\|(r.splice(o,0,n,i),o+=2)}if(r.length>4)for(let t=0;t<r.length;t+=2){const e=(t+2)%r.length,n=(t+4)%r.length;(r[t]===r[e]&&r[e]===r[n]\|\|r[t+1]===r[e+1]&&r[e+1]===r[n+1])&&(r.splice(e,2),t-=2)}return o}_project(t,e,n,r){let o,i,s,a=1/0;if(r<0){if(e<=this.ymin)return null;(o=(this.ymin-e)/r)<a&&(s=this.ymin,i=t+(a=o)n)}else if(r>0){if(e>=this.ymax)return null;(o=(this.ymax-e)/r)<a&&(s=this.ymax,i=t+(a=o)n)}if(n>0){if(t>=this.xmax)return null;(o=(this.xmax-t)/n)<a&&(i=this.xmax,s=e+(a=o)r)}else if(n<0){if(t<=this.xmin)return null;(o=(this.xmin-t)/n)<a&&(i=this.xmin,s=e+(a=o)r)}return[i,s]}_edgecode(t,e){return(t===this.xmin?1:t===this.xmax?2:0)\|(e===this.ymin?4:e===this.ymax?8:0)}_regioncode(t,e){return(t<this.xmin?1:t>this.xmax?2:0)\|(e<this.ymin?4:e>this.ymax?8:0)}}const uo=2Math.PI,fo=Math.pow;function ho(t){return t[0]}function po(t){return t[1]}function mo(t,e,n){return[t+Math.sin(t+e)n,e+Math.cos(t-e)n]}class go{static from(t,e=ho,n=po,r){return new go("length"in t?function(t,e,n,r){const o=t.length,i=new Float64Array(2o);for(let s=0;s<o;++s){const o=t[s];i[2s]=e.call(r,o,s,t),i[2s+1]=n.call(r,o,s,t)}return i}(t,e,n,r):Float64Array.from(function(t,e,n,r){let o=0;for(const i of t)yield e.call(r,i,o,t),yield n.call(r,i,o,t),++o}(t,e,n,r)))}constructor(t){this._delaunator=new Kr(t),this.inedges=new Int32Array(t.length/2),this._hullIndex=new Int32Array(t.length/2),this.points=this._delaunator.coords,this._init()}update(){return this._delaunator.update(),this._init(),this}_init(){const t=this._delaunator,e=this.points;if(t.hull&&t.hull.length>2&&function(t){const{triangles:e,coords:n}=t;for(let t=0;t<e.length;t+=3){const r=2e[t],o=2e[t+1],i=2e[t+2];if((n[i]-n[r])(n[o+1]-n[r+1])-(n[o]-n[r])(n[i+1]-n[r+1])>1e-10)return!1}return!0}(t)){this.collinear=Int32Array.from({length:e.length/2},((t,e)=>e)).sort(((t,n)=>e[2t]-e[2n]\|\|e[2t+1]-e[2n+1]));const t=this.collinear[0],n=this.collinear[this.collinear.length-1],r=[e[2t],e[2t+1],e[2n],e[2n+1]],o=1e-8Math.hypot(r[3]-r[1],r[2]-r[0]);for(let t=0,n=e.length/2;t<n;++t){const n=mo(e[2t],e[2t+1],o);e[2t]=n[0],e[2t+1]=n[1]}this._delaunator=new Kr(e)}else delete this.collinear;const n=this.halfedges=this._delaunator.halfedges,r=this.hull=this._delaunator.hull,o=this.triangles=this._delaunator.triangles,i=this.inedges.fill(-1),s=this._hullIndex.fill(-1);for(let t=0,e=n.length;t<e;++t){const e=o[t%3==2?t-2:t+1];-1!==n[t]&&-1!==i[e]\|\|(i[e]=t)}for(let t=0,e=r.length;t<e;++t)s[r[t]]=t;r.length<=2&&r.length>0&&(this.triangles=new Int32Array(3).fill(-1),this.halfedges=new Int32Array(3).fill(-1),this.triangles[0]=r[0],i[r[0]]=1,2===r.length&&(i[r[1]]=0,this.triangles[1]=r[1],this.triangles[2]=r[1]))}voronoi(t){return new co(this,t)}neighbors(t){const{inedges:e,hull:n,_hullIndex:r,halfedges:o,triangles:i,collinear:s}=this;if(s){const e=s.indexOf(t);return e>0&&(yield s[e-1]),void(e<s.length-1&&(yield s[e+1]))}const a=e[t];if(-1===a)return;let l=a,c=-1;do{if(yield c=i[l],l=l%3==2?l-2:l+1,i[l]!==t)return;if(l=o[l],-1===l){const e=n[(r[t]+1)%n.length];return void(e!==c&&(yield e))}}while(l!==a)}find(t,e,n=0){if((t=+t)!=t\|\|(e=+e)!=e)return-1;const r=n;let o;for(;(o=this._step(n,t,e))>=0&&o!==n&&o!==r;)n=o;return o}_step(t,e,n){const{inedges:r,hull:o,_hullIndex:i,halfedges:s,triangles:a,points:l}=this;if(-1===r[t]\|\|!l.length)return(t+1)%(l.length>>1);let c=t,u=fo(e-l[2t],2)+fo(n-l[2t+1],2);const f=r[t];let d=f;do{let r=a[d];const f=fo(e-l[2r],2)+fo(n-l[2r+1],2);if(f<u&&(u=f,c=r),d=d%3==2?d-2:d+1,a[d]!==t)break;if(d=s[d],-1===d){if(d=o[(i[t]+1)%o.length],d!==r&&fo(e-l[2d],2)+fo(n-l[2d+1],2)<u)return d;break}}while(d!==f);return c}render(t){const e=null==t?t=new ao:void 0,{points:n,halfedges:r,triangles:o}=this;for(let e=0,i=r.length;e<i;++e){const i=r[e];if(i<e)continue;const s=2o[e],a=2o[i];t.moveTo(n[s],n[s+1]),t.lineTo(n[a],n[a+1])}return this.renderHull(t),e&&e.value()}renderPoints(t,e){void 0!==e\|\|t&&"function"==typeof t.moveTo\|\|(e=t,t=null),e=null==e?2:+e;const n=null==t?t=new ao:void 0,{points:r}=this;for(let 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0),a.gene2\|\|(a.isoform2=void 0),a.gene1){n.good++;const t={dt:i?o.dtsv:o.dtfusionrna,class:i?o.mclasssv:o.mclassfusionrna,isoform:a.isoform1,mname:a.gene2\|\|a.chr2,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene1.toUpperCase():a.gene1;n.data[e]\|\|(n.data[e]=[]),n.data[e].push(t)}if(a.gene2&&a.gene2!=a.gene1){n.good++;const t={dt:i?o.dtsv:o.dtfusionrna,class:i?o.mclasssv:o.mclassfusionrna,isoform:a.isoform2,mname:a.gene1\|\|a.chr1,sample:a.sample,patient:a.patient,sampletype:a.sampletype,origin:a.origin,disease:a.disease,pairlst:[{a:{name:a.gene1,isoform:a.isoform1,strand:a.strand1,chr:a.chr1,position:a.position1},b:{name:a.gene2,isoform:a.isoform2,strand:a.strand2,chr:a.chr2,position:a.position2}}]},e=n.geneToUpper?a.gene2.toUpperCase():a.gene2;n.data[e]\|\|(n.data[e]=[]),n.data[e].push(t)}}}else c.push([t,"missing position2",s])}function a(t){const e={};for(const n in t){if("pairlst"==n)continue;const r=t[n];"object"!=typeof r&&(e[n]=r)}if(t.pairlst){e.pairlst=[];for(const n of t.pairlst){const t={};for(const e in n)"a"!=e&&"b"!=e&&"interstitial"!=e&&(t[e]=n[e]);if(n.a){t.a={};for(const e in n.a){const r=n.a[e];"object"!=typeof r&&(t.a[e]=r)}}if(n.b){t.b={};for(const e in n.b){const r=n.b[e];"object"!=typeof r&&(t.b[e]=r)}}if(n.interstitial){t.interstitial={};for(const e in n.interstitial){const 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u){if(t.a&&t.a.name&&t.a.isoform){n.good++;const e={dt:r.dtfusionrna,class:r.mclassfusionrna,isoform:t.a.isoform,mname:t.b.name};for(const t in l)"jsontext"!=t&&(e[t]=l[t]);e.pairlst=a(u);const o=t.a.name.toUpperCase();n.data[o]\|\|(n.data[o]=[]),n.data[o].push(e)}if(t.b&&t.b.name&&t.b.isoform){n.good++;const e={dt:r.dtfusionrna,class:r.mclassfusionrna,isoform:t.b.isoform,mname:t.a.name};for(const t in l)"jsontext"!=t&&(e[t]=l[t]);e.pairlst=a(u);const o=t.b.name.toUpperCase();n.data[o]\|\|(n.data[o]=[]),n.data[o].push(e)}}else{switch(u.dt=u.typecode,delete u.typecode,u.dt){case r.dtitd:u.class=r.mclassitd,u.mname="ITD";break;case r.dtnloss:u.class=r.mclassnloss,u.mname="N-loss";break;case r.dtcloss:u.class=r.mclasscloss,u.mname="C-loss";break;case r.dtdel:u.class=r.mclassdel,u.mname="Del";break;case r.dtsv:u.class=r.mclasssv,u.mname="SV";break;default:return void c.push([t,"unknown datatype",s])}if(!u.gene)return void c.push([t,"json.gene missing",s]);n.good++;for(const t in 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r=n(1495);const o=n(502),i=n(2554),s=(0,r.B8)("#8AB1D4").darker(),a=(0,r.B8)("#aaa").darker().darker(),l="#4F8053",c=!0,u=!1,f=1,d=2,h=3,p=4,m=5,g=6,y=7,v=8,b=9,_=10,w={[f]:"SNV/indel",[d]:"Fusion RNA",[p]:"CNV",[m]:"SV",[g]:"ITD",[y]:"Deletion",[v]:"N-loss",[b]:"C-loss",[_]:"LOH",[h]:"Gene Expression"},x={M:{label:"MISSENSE",color:"#3987CC",dt:f,desc:"A substitution variant in the coding region resulting in altered protein coding.",key:"M"},E:{label:"EXON",color:"#bcbd22",dt:f,desc:"A variant in the exon of a non-coding RNA.",key:"E"},F:{label:"FRAMESHIFT",color:"#db3d3d",dt:f,desc:"An insertion or deletion variant that alters the protein coding frame.",key:"F"},N:{label:"NONSENSE",color:"#ff7f0e",dt:f,desc:"A variant altering protein coding to produce a premature stopgain or stoploss.",key:"N"},S:{label:"SILENT",color:"#2ca02c",dt:f,desc:"A substitution variant in the coding region that does not alter protein coding.",key:"S"},D:{label:"PROTEINDEL",color:"#7f7f7f",dt:f,desc:"A deletion resulting in a loss of one or more codons from the product, but not altering the protein coding frame.",key:"D"},I:{label:"PROTEININS",color:"#8c564b",dt:f,desc:"An insertion introducing one or more codons into the product, but not altering the protein coding frame.",key:"I"},P:{label:"SPLICE_REGION",color:"#9467bd",dt:f,desc:"A variant in an intron within 10 nt of an exon boundary.",key:"P"},L:{label:"SPLICE",color:"#6633FF",dt:f,desc:"A variant near an exon edge that may affect splicing functionality.",key:"L"},Intron:{label:"INTRON",color:"#656565",dt:f,desc:"An intronic variant.",key:"Intron"},Blank:{label:"Not tested",color:"#fff",dt:f,desc:"This gene is not tested.",key:"Blank"},WT:{label:"Wildtype",color:"#D3D3D3",dt:f,desc:"Wildtype",key:"WT"}},k="ITD";x[k]={label:"ITD",color:"#ff70ff",dt:g,desc:"In-frame internal tandem duplication.",key:k};const q="DEL";x[q]={label:"DELETION, intragenic",color:"#858585",dt:y,desc:"Intragenic deletion.",key:q};const N="NLOSS";x[N]={label:"N-terminus loss",color:"#545454",dt:v,desc:"N-terminus loss due to translocation",key:N};const S="CLOSS";x[S]={label:"C-terminus loss",color:"#545454",dt:b,desc:"C-terminus loss due to translocation",key:S};const A="Utr3";x[A]={label:"UTR_3",color:"#998199",dt:f,desc:"A variant in the 3' untranslated region.",key:A};const M="Utr5";x[M]={label:"UTR_5",color:"#819981",dt:f,desc:"A variant in the 5' untranslated region.",key:M};const T="X";x[T]={label:"NONSTANDARD",color:"black",dt:f,desc:"A mutation class that either does not match our notation, or is unspecified.",key:T};const C="noncoding";function j(t){switch(t.toLowerCase()){case"missense_mutation":return"M";case"nonsense_mutation":case"nonstop_mutation":return"N";case"splice_site":return"L";case"rna":case"3'flank":case"5'flank":return C;case"frame_shift_del":case"frame_shift_ins":return"F";case"in_frame_del":return"D";case"in_frame_ins":return"I";case"translation_start_site":return T;case"3'utr":return A;case"5'utr":return M;case"blank":return"Blank";default:return null}}x[C]={label:"NONCODING",color:"black",dt:f,desc:"Noncoding mutation.",key:C};const O="Fuserna";x[O]={label:"Fusion transcript",color:"#545454",dt:d,desc:"Marks the break points leading to fusion transcripts.<br><span style=\"font-size:150%\">◐</span> - 3' end of the break point is fused to the 5' end of another break point in a different gene.<br><span style=\"font-size:150%\">◑</span> - 5' end of the break point is fused to the 3' end of another break point in a different gene.",key:O};const E="SV";x[E]={label:"Structural variation",color:"#858585",dt:m,desc:"Structural variation detected in genomic DNA.",key:E};const R="CNV_amp";x[R]={label:"Copy number gain",color:"#e9a3c9",dt:p,desc:"Copy number gain",key:R};const I="CNV_loss";x[I]={label:"Copy number loss",color:"#a1d76a",dt:p,desc:"Copy number loss",key:I};const P="CNV_loh";x[P]={label:"LOH",color:"#12EDFC",dt:p,desc:"Loss of heterozygosity",key:P};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>',G={},U="S";G[U]={label:"Somatic",desc:"A variant found only in a tumor sample. 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t>=1e9?(t/1e9).toFixed(1)+" Gb":t>=1e7?Math.ceil(t/1e6)+" Mb":t>=1e6?(t/1e6).toFixed(1)+" Mb":t>=1e4?Math.ceil(t/1e3)+" Kb":t>=1e3?(t/1e3).toFixed(1)+" Kb":t+(e?"bytes":" bp")}const ot={A:"#ca0020",T:"#f4a582",C:"#92c5de",G:"#0571b0"};function it(t){switch(t){case"A":return"T";case"T":return"A";case"C":return"G";case"G":return"C";case"a":return"t";case"t":return"a";case"c":return"g";case"g":return"c";default:return t}}function st(t){const e=[];for(let n=t.length-1;n>=0;n--)e.push(it(t[n]));return e.join("")}function at(t,e){const n={chr:t.chr,start:t.start,stop:t.stop,strand:t.strand,coding:[]};if(e.isskipexon\|\|e.isaltexon)for(let r=0;r<t.exon.length;r++){const o=Math.max(t.codingstart,t.exon[r][0]),i=Math.min(t.codingstop,t.exon[r][1]);o>i\|\|-1==e.skippedexon.indexOf(r)&&n.coding.push([o,i])}else if(e.a5ss\|\|e.a3ss){const 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e=s[i.groupsamplebyattr.attrlst[t].k];if(null==e)break;l.push(e)}l.unshift(a);const c=l.join(i.groupsamplebyattr.attrnamespacer);if(!n.has(c)){const t=[];for(const e of i.groupsamplebyattr.attrlst){const n=s[e.k];if(null==n)break;const r={k:e.k,kvalue:n};e.full&&(r.full=e.full,r.fullvalue=s[e.full]),t.push(r)}const e=[];for(const t of i.groupsamplebyattr.attrlst){const n=s[t.k];if(null==n)break;const r=(t.full?s[t.full]:null)\|\|n;e.push(r)}n.set(c,{name:c,samples:[],attributes:t})}let u=!0;for(const r of n.get(c).samples)if(r.samplename==t){for(const t of e)r.items.push(t);u=!1;break}u&&n.get(c).samples.push({samplename:t,items:e})}function $t(t){return Number.isFinite(t.dna_mintotalreads)?Number.isFinite(t.rna_mintotalreads)?Number.isFinite(t.hetsnp_minbaf)?Number.isFinite(t.hetsnp_maxbaf)?Number.isFinite(t.rnapileup_q)?Number.isFinite(t.rnapileup_Q)?void 0:"invalid value for rnapileup_Q":"invalid value for rnapileup_q":"invalid value for hetsnp_maxbaf":"invalid value for 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o=[];for(const i of n)if(i.type==k.tkt.mdsvcf){const[n,s]=oe(t,e,i,r);if(n)return[n];o.push(s)}else{if(i.type!=k.tkt.mdssvcnv)return["unsupported track type: "+i.type];{const[e,n]=ne(t,0,i,r);if(e)return[e];o.push(n)}}return[null,Promise.all(o).then((t=>{const e=[];for(const n of t)for(const t of n.items)e.push(t);return{id:t[0].id,items:e}}))]}function oe(t,e,n,i){if(!n.tracks)return"tracks[] missing from dsquery";if(!t.chr)return["chr missing"];if(!Number.isInteger(t.start)\|\|!Number.isInteger(t.stop))return["invalid start/stop coordinate"];if(t.stop-t.start>3e6)return["look range too big (>3Mb)"];const s=[];for(const e of n.tracks){const a=Promise.resolve().then((()=>{if(!e.file)return x.cache_index(e.url,e.indexURL)})).then((s=>new Promise(((a,l)=>{const c=[],f=m(vt,[e.file?u.join(o.tpmasterdir,e.file):e.url,(e.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1)],{cwd:s});_.createInterface({input:f.stdout}).on("line",(r=>{if(n.iscustom)c.push(r);else if(e.type==k.mdsvcftype.vcf){const[o,s,a]=q.vcfparseline(r,{nochr:e.nochr,samples:e.samples,info:n.info,format:e.format});for(const e of s)if(e.sampledata&&(k.vcfcopymclass(e,{}),!(t.snvindel&&t.snvindel.excludeclasses&&t.snvindel.excludeclasses[e.class]))){if(i){const t=[];for(const n of e.sampledata)i.has(n.sampleobj.name)&&t.push(n);if(0==t.length)continue;e.sampledata=t}for(const t of e.sampledata)delete t.allele2readcount;delete e._m,delete e.vcf_ID,delete e.name,e.dt=k.dtsnvindel,c.push(e)}}else console.error("type not one of mdsvcftype: "+e.type)}));const d=[];f.stderr.on("data",(t=>d.push(t))),f.on("close",(t=>{const e=d.join("");!e\|\|r(e)?a(c):l(e)}))}))));s.push(a)}return[null,Promise.all(s).then((e=>{const n=[];for(const t of e)for(const e of t)n.push(e);return{id:t.id,items:n}}))]}function ie(t){if(!t.endsWith(".gz"))return["no .gz suffix (file should be compressed by bgzip)"];const e=u.join(o.tpmasterdir,t);return c.existsSync(e)?c.existsSync(e+".tbi")\|\|c.existsSync(e+".csi")?[null,e]:[".tbi/.csi index missing"]:[".gz file not found"]}kt.get(qt+"/cardsjson",(async function(t,e){try{if(t.query.datafile&&t.query.tabixCoord)return new Promise(((n,r)=>{const i=m(vt,[u.join(o.tpmasterdir,t.query.datafile),t.query.tabixCoord]),s=[],a=[];i.stdout.on("data",(t=>s.push(t))),i.stderr.on("data",(t=>a.push(t))),i.on("close",(t=>{""!=a.join("").trim()&&r("error querying bedj file");const o=s.join("").trim();n(e.send({file:o.split("\n")}))}))})).catch((t=>{t.stack&&console.error(t.stack)}));throw"invalid cards request"}catch(t){e.send({error:t.message\|\|t})}})),kt.post(qt+"/mdsjsonform",(async function(t,n){if(!e.features.mdsjsonform)return n.send({error:"This feature is not enabled on this server."});if(t.query.deposit){const e=Math.random().toString(),r=await function(){const t=u.join(o.cachedir,"mdsjsonform");return new Promise(((e,n)=>{c.stat(t,((r,o)=>{if(r){if("ENOENT"==r.code)return void 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yt)yt[t].blat&&(s=!0);n.send({genomes:i,debugmode:o.debugmode,headermessage:o.headermessage,base_zindex:o.base_zindex,codedate:mt.codedate,launchdate:mt.launchdate,hasblat:s,features:e.features,dsAuth:ft.getDsAuth(t),commonOverrides:o.commonOverrides,targetPortal:o.targetPortal,cardsPath:null===(r=o.cards)\|\|void 0===r?void 0:r.path})})),kt.get(qt+"/getDataset",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.datasets)throw"genomeobj.datasets{} missing";let r;for(const e in n.datasets)if(e.toLowerCase()==t.query.dsname.toLowerCase()){r=n.datasets[e];break}if(!r)throw"invalid dsname";return r.isMds3?e.send({ds:X.client_copy(r,null,null,kt,qt)}):r.isMds?e.send({ds:Tt(r)}):e.send({ds:Mt(r)})}catch(t){e.send({error:t.message\|\|t})}})),kt.all(qt+"/ntseq",(async function(t,e){try{if(!t.query.coord)throw"coord missing";const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.genomefile)throw"no sequence file available";const r=await x.get_fasta(n,t.query.coord);e.send({seq:r.split("\n").slice(1).join("")})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/pdomain",(function(t,e){try{const n=t.query.genome;if(!n)throw"no genome";const r=yt[n];if(!r)throw"invalid genome "+n;if(!r.proteindomain)return e.send({lst:[]});if(!Array.isArray(t.query.isoforms))throw"isoforms[] missing";const o=[];for(const e of t.query.isoforms){if(r.genomicNameRegexp.test(e))continue;const t=r.proteindomain.getbyisoform.all(e);o.push({name:e,pdomains:t.map((t=>{const n=JSON.parse(t.data);return n.refseq=e,n}))})}e.send({lst:o})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/tkbedj",H(yt)),kt.post(qt+"/tkbedgraphdot",z(yt)),kt.all(qt+"/tkbam",B(yt)),kt.get(qt+"/gdcbam",Z),kt.get(qt+"/gdc_ssms",G.handle_gdc_ssms(yt)),kt.get(qt+"/gdc_filter2topGenes",G.handle_filter2topGenes(yt)),kt.get(qt+"/tkaicheck",U(yt)),kt.get(qt+"/blat",V(yt)),kt.all(qt+"/mds3",Y(yt)),kt.get(qt+"/tkbampile",W),kt.post(qt+"/dsdata",(async function(t,e){try{if(!yt[t.query.genome])throw"invalid genome";if(!t.query.dsname)throw".dsname missing";const n=yt[t.query.genome].datasets[t.query.dsname];if(!n)throw"invalid dsname";const r=[];for(const e of n.queries)if((!t.query.expressiononly\|\|e.isgeneexpression)&&!(t.query.noexpression&&e.isgeneexpression\|\|e.dsblocktracklst))if(e.vcffile){const n=await Et(e,t);r.push(n)}else{if(!e.makequery)throw"unknow type from one of ds.queries[]";{const o=Ot(n,e,t);r.push(o)}}e.send({data:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/tkbigwig",F),kt.post(qt+"/tkld",L(yt)),kt.get(qt+"/tabixheader",(async function(t,e){St(t);try{const[n,r,o]=ce(t);if(n)throw n;const i=o?await x.cache_index(r,t.query.indexURL):null,s=await x.get_header_tabix(r,i);e.send({lines:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.all(qt+"/snp",(async function(t,e){try{const n=t.query.genome;if(!n)throw"no genome";e.send({results:await Ct(t.query,yt[n])})}catch(t){return t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.get(qt+"/clinvarVCF",(async function(t,e){St(t);try{const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.clinvarVCF)throw"no clinvar for this genome";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos is not integer";if(r<0)throw"pos is not positive integer";if(!t.query.chr)throw"chr missing";{const e=n.chrlookup[t.query.chr.toUpperCase()];if(!e)throw"invalid chr";if(r>e.len)throw"pos out of bound"}let o;if(await x.get_lines_bigfile({args:[n.clinvarVCF.file,(n.clinvarVCF.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+r+"-"+(r+1)],callback:e=>{const[i,s,a]=q.vcfparseline(e,n.clinvarVCF);for(const e of s)e.pos==r&&e.ref==t.query.ref&&e.alt==t.query.alt&&(o=e)}}),!o)return e.send({});const i=o.info[n.clinvarVCF.infokey],s=n.clinvarVCF.categories[i];e.send({hit:{id:o.vcf_ID,value:s?s.label:i,bg:s?s.color:"#858585",textcolor:s&&s.textcolor?s.textcolor:"black"}})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/isoformlst",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!Array.isArray(t.query.lst))throw".lst missing";const r=[];for(const e of t.query.lst){if(n.genomicNameRegexp.test(e))continue;const t=n.genedb.getjsonbyisoform.all(e);r.push(t.map((t=>{const e=JSON.parse(t.genemodel);return t.isdefault&&(e.isdefault=!0),e})))}e.send({lst:r})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/dbdata",(function(t,e){})),kt.get(qt+"/img",(async function(t,e){St(t);const[n,r,o]=ce(t);try{if(n)throw"invalid image file";const t=await c.promises.readFile(r);e.send({src:"data:image/jpeg;base64,"+new Buffer.from(t).toString("base64"),size:b(r)})}catch(n){e.send({error:n.message\|\|n})}})),kt.post(qt+"/svmr",(function(t,e){if(t.query.file){const[n,r,o]=ce(t);if(n)return void e.send({error:"illegal file name"});c.readFile(r,"utf8",((t,n)=>{t?e.send({error:"cannot read file"}):e.send({raw:n})}))}else e.send({error:"missing file"})})),kt.post(qt+"/study",(async function(t,e){try{if(le(t.query.file))throw"invalid file path";const n=u.join(o.tpmasterdir,t.query.file.endsWith(".json")?t.query.file:t.query.file+".json"),r=JSON.parse(await x.read_file(n));if(!r.genome)throw"genome missing";const i={};let s=0;for(const t of r.mutationset\|\|[]){const e=N.init_bulk_flag(r.genome);if(!e)throw"init_bulk_flag() failed";if(r.mutationset.length>1&&(e.tpsetname=t.name?t.name:"set"+ ++s),i[Math.random()]=e,t.snvindel){const n=(await x.read_file(u.join(o.tpmasterdir,t.snvindel))).trim().split(/\r?\n/),r=S.parseheader(n[0],e);if(r)throw"snvindel header line error: "+r;for(let t=1;t<n.length;t++)S.parseline(t,n[t],e)}if(t.sv){const n=(await x.read_file(u.join(o.tpmasterdir,t.sv))).trim().split(/\r?\n/),r=C.parseheader(n[0],e,!0);if(r)throw"sv header line error: "+r;for(let t=1;t<n.length;t++)C.parseline(t,n[t],e,!0)}if(t.fusion){const n=(await x.read_file(u.join(o.tpmasterdir,t.fusion))).trim().split(/\r?\n/),r=C.parseheader(n[0],e,!1);if(r)throw"fusion header line error: "+r;for(let t=1;t<n.length;t++)C.parseline(t,n[t],e,!1)}if(t.svjson){const n=(await x.read_file(u.join(o.tpmasterdir,t.svjson))).trim().split(/\r?\n/),[r,i]=j.parseheader(n[0],e);if(r)throw"svjson header line error: "+r;for(let t=1;t<n.length;t++)j.parseline(t,n[t],e,i)}if(t.cnv){const n=(await x.read_file(u.join(o.tpmasterdir,t.cnv))).trim().split(/\r?\n/),r=A.parseheader(n[0],e);if(r)throw"cnv header line error: "+r;for(let t=1;t<n.length;t++)A.parseline(t,n[t],e)}if(t.itd){const n=(await x.read_file(u.join(o.tpmasterdir,t.itd))).trim().split(/\r?\n/),r=T.parseheader(n[0],e);if(r)throw"itd header line error: "+r;for(let t=1;t<n.length;t++)T.parseline(t,n[t],e)}if(t.deletion){const n=(await x.read_file(u.join(o.tpmasterdir,t.deletion))).trim().split(/\r?\n/),r=M.parseheader(n[0],e);if(r)throw"deletion header line error: "+r;for(let t=1;t<n.length;t++)M.parseline(t,n[t],e)}if(t.truncation){const n=(await x.read_file(u.join(o.tpmasterdir,t.truncation))).trim().split(/\r?\n/),r=O.parseheader(n[0],e);if(r)throw"Truncation header line error: "+r;for(let t=1;t<n.length;t++)O.parseline(t,n[t],e)}}if(r.annotations){const t=r.annotations.idkey?r.annotations.idkey:"sample";r.annotations.data={};for(const e of r.annotations.files){const n=await x.read_file(u.join(o.tpmasterdir,e));R.tsvParse(n).forEach((e=>{const n=e[t].trim();r.annotations.data[n]\|\|(r.annotations.data[n]=[]),r.annotations.data[n].push(e)}))}}for(const t in i)se(i[t]);delete r.mutationset,e.send({cohort:r,flagset:i})}catch(t){return void e.send({error:t.message\|\|t})}})),kt.post(qt+"/textfile",(function(t,e){if(!t.query.file)return e.send({error:"no file"});if(le(t.query.file))return e.send({error:"invalid file name"});const n=u.join(o.tpmasterdir,t.query.file);if(null!=t.query.from){if(!Number.isInteger(t.query.from))return void e.send({error:"invalid value for from"});if(!Number.isInteger(t.query.to))return void e.send({error:"invalid value for to"});const r=[];d(c.createReadStream(n)).on("end",(()=>{e.send({text:r.join("\n")})})).lines.map(String).skip(t.query.from-1).take(t.query.to).forEach((t=>{r.push(t)}))}else c.readFile(n,{encoding:"utf8"},((t,n)=>{t?e.send({error:"error reading file"}):e.send({text:n})}))})),kt.post(qt+"/urltextfile",(async function(t,e){const n=t.query.url.replace(o.URL,`http://127.0.0.1:${o.port}`);try{const t=await f(n);switch(t.statusCode){case 200:return void e.send({text:x.stripJsScript(t.body)});case 404:return void e.send({error:"File not found: "+n});default:e.send({error:"unknown status code: "+t.status})}}catch(t){return e.send({error:"Error downloading file: "+n})}})),kt.get(qt+"/junction",J),kt.post(qt+"/mdsjunction",$(yt)),kt.post(qt+"/mdscnv",(function(t,e){const[n,i,s,a]=Rt(t.query);if(n)return e.send({error:n});if(!t.query.rglst)return e.send({error:"rglst missing"});if(!t.query.gain)return e.send({error:".gain missing"});if(!t.query.loss)return e.send({error:".loss missing"});if(a.viewrangeupperlimit){if(t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>=a.viewrangeupperlimit)return e.send({error:"zoom in under "+k.bplen(a.viewrangeupperlimit)+" to view details"})}if(t.query.permanentHierarchy){const n=function(t,e){if(!e.cohort)return".cohort missing from ds";if(!e.cohort.hierarchies)return".hierarchies missing from ds.cohort";if(!e.cohort.hierarchies.lst)return".hierarchies.lst[] missing from ds.cohort";const n=e.cohort.hierarchies.lst.find((e=>e.name==t.permanentHierarchy.hierarchyname));if(!n)return"unknown hierarchy "+t.permanentHierarchy.hierarchyname;if(!n.levels)return".levels[] missing in hierarchy "+n.name;const r=n.levels[t.permanentHierarchy.levelidx];if(!r)return"level not found by array idx "+t.permanentHierarchy.levelidx;const o=r.k;return delete t.cohortHiddenAttr,t.cohortOnlyAttr={},t.cohortOnlyAttr[o]={},t.cohortOnlyAttr[o][t.permanentHierarchy.valuekey]=1,null}(t.query,s);if(n)return e.send({error:"permanentHierarchy error: "+n})}const l=[],c={count:0,samples:new Set},f={count:0,samples:new Set};for(const e of t.query.rglst){const n=new Promise(((n,i)=>{const l=m(vt,[a.file?u.join(o.tpmasterdir,a.file):a.url,e.chr+":"+e.start+"-"+e.stop],{cwd:a.usedir}),d=_.createInterface({input:l.stdout}),h=(e.stop-e.start)/e.width,p=[];for(let t=0;t<e.width;t++)p.push({positive:0,negative:0});d.on("line",(n=>{const r=n.split("\t"),o=Number.parseInt(r[1]),i=Number.parseInt(r[2]);if(t.query.bplengthUpperLimit&&i-o>t.query.bplengthUpperLimit)return;const a=JSON.parse(r[3]);if(t.query.valueCutoff&&Math.abs(a.value)<t.query.valueCutoff)return;if(a.sample&&s.cohort&&s.cohort.annotation){const e=s.cohort.annotation[a.sample];if(!e)return;if(t.query.cohortOnlyAttr&&s.cohort&&s.cohort.annotation){let n=!1;for(const r in t.query.cohortOnlyAttr){const o=e[r];if(o&&t.query.cohortOnlyAttr[r][o]){n=!0;break}}if(!n)return}if(t.query.cohortHiddenAttr&&s.cohort.attributes){let n=!1;for(const r in t.query.cohortHiddenAttr){s.cohort.attributes.lst.find((t=>t.key==r)).isNumeric;const o=e[r];if(o){if(t.query.cohortHiddenAttr[r][o]){n=!0;break}}else if(t.query.cohortHiddenAttr[r][xt]){n=!0;break}}if(n)return}}a.value>0?(c.count++,c.samples.add(a.sample)):a.value<0&&(f.count++,f.samples.add(a.sample));const l=Math.max(e.start,o),u=Math.min(e.stop,i);let d,m;e.reverse?(d=Math.floor((e.stop-u)/h),m=Math.floor((e.stop-l)/h)):(d=Math.floor((l-e.start)/h),m=Math.floor((u-e.start)/h));for(let t=d;t<m;t++)a.value>0?p[t].positive++:a.value<0&&p[t].negative++}));const g=[];l.stderr.on("data",(t=>g.push(t))),l.on("close",(t=>{const e=g.join("");!e\|\|r(e)?n(p):i(e)}))}));l.push(n)}Promise.all(l).then((n=>{const r=t.query.rglst.reduce(((e,n)=>e+n.width+t.query.regionspace),0)-t.query.regionspace,o=g(r,t.query.gain.barheight+t.query.loss.barheight),i=o.getContext("2d"),l={gain:{count:c.count,samplenumber:c.samples.size},loss:{count:f.count,samplenumber:f.samples.size},maxvalue:0};if(c.count+f.count==0)return i.font="15px Arial",i.fillStyle="#aaa",i.textAlign="center",i.textBaseline="middle",i.fillText("No data in view 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e=t.sampledata.filter((t=>p.set.has(t.sampleobj.name)));if(!e.length)continue;t.sampledata=e}if(d){const e=[];for(const n of t.sampledata){let t=!0;for(const e in d){let r=n[e];if(null==r&&(r=k.not_annotated),d[e].has(r)){t=!1;break}}t&&e.push(n)}if(0==e.length)continue;t.sampledata=e}if(h&&n.cohort&&n.cohort.annotation){const e=[];for(const r of t.sampledata){const t=n.cohort.annotation[r.sampleobj.name];if(!t)continue;let o=!0;for(const e in h){const n=t[e];if(h[e].has(n)){o=!1;break}}o&&e.push(r)}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=k.dtsnvindel,i.push(t)}}else console.error('unknown "type" from a vcf file')}));const b=[];v.stderr.on("data",(t=>b.push(t))),v.on("close",(t=>{const e=b.join("");!e\|\|r(e)?c():y(e)}))}));c.push(y)}return Promise.all(c).then((()=>i))}));v.push(e)}return Promise.all(v).then((t=>{const e=[];for(const n of t)for(const t of n)if(t.dt!=k.dtsnvindel)console.error("unknown dt: "+t.dt);else{if(!t.sampledata)continue;let n=!0;for(const r of e)if(t.chr==r.chr&&t.pos==r.pos&&t.ref==r.ref&&t.alt==r.alt){for(const e of t.sampledata)r.sampledata.push(e);n=!1;break}n&&e.push(t)}return e.sort(((t,e)=>t.pos-e.pos)),[null,e]}))}(i,s,a,t,d,h,0,f,g,p),S=function(t){const e=new Map;for(const n of t)for(const t of n){if(!t.sample)continue;const n=t.sample;e.has(n)\|\|e.set(n,[]),t._chr?e.get(n).push(t):(delete t.sample,delete t.sampletype,e.get(n).push(t))}return e}(y);if(t.query.singlesample){const e={lst:S.get(t.query.singlesample)};return w?e.vcfrangelimit=w:e.data_vcf=N,void n.send(e)}const A={samplegroups:Dt(s,a,y,N,S,p),vcfrangelimit:w,data_vcf:N};t.query.getallsamples&&a.allow_getallsamples&&(A.getallsamples=!0);a.checkrnabam?await async function(t,e,n,r){if(!n.checkvcf)return;if(t.stop-t.start>=5e5)return void(r.expressionrangelimit=5e5);const o=e.tracks.find((t=>t.__isgene)),i=await Wt(e,o,t.chr,t.start,t.stop);let s,a=null;for(const t of i.values())null==a?(a=t.start,s=t.stop):(a=Math.min(a,t.start),s=Math.max(s,t.stop));await It(i,t.chr,a,s,n,r)}(t.query.rglst[0],i,a,A):function(t,e,n,r){if(n)return void(t.expressionrangelimit=n);if(r){t.gene2coord={};for(const[e,n]of r)t.gene2coord[e]={chr:n.chr,start:n.start,stop:n.stop};if(0==t.samplegroups.length)return;if(t.getallsamples){const e=new Set(t.samplegroups[0].samples.map((t=>t.samplename))),n=new Set;for(const[t,o]of r)for(const t of o.samples.keys())e.has(t)\|\|n.add(t);for(const e of n)t.samplegroups[0].samples.push({samplename:e,items:[]})}for(const n of t.samplegroups){const t=new Map;for(const[o,i]of r){t.set(o,[]);for(const[r,s]of i.samples)if(n.attributes&&e.cohort&&e.cohort.annotation){const i=e.cohort.annotation[r];if(!i)continue;let a=!0;for(const t of n.attributes)if(i[t.k]!=t.kvalue){a=!1;break}a&&t.get(o).push(s)}else t.get(o).push(s)}for(const[e,n]of t)n.sort(((t,e)=>t.value-e.value));for(const e of n.samples){e.expressionrank={};for(const[n,o]of t){const t=r.get(n).samples.get(e.samplename);if(null==t)continue;const i=Vt(t.value,o);e.expressionrank[n]={rank:i};for(const r in t)e.expressionrank[n][r]=t[r]}}}}}(A,s,v,b);(function(t,e){if(t.cohort&&t.cohort.sampleAttribute&&t.cohort.sampleAttribute.attributes&&t.cohort.annotation){e.sampleannotation={};const n=[];for(const e in t.cohort.sampleAttribute.attributes){t.cohort.sampleAttribute.attributes[e].clientnoshow\|\|n.push(e)}for(const r of e.samplegroups)for(const o of r.samples){const r=t.cohort.annotation[o.samplename];if(r){const t={};let i=!1;for(const e of n){const n=r[e];null!=n&&(i=!0,t[e]=n)}i&&(e.sampleannotation[o.samplename]=t)}}}})(s,A),n.send(A)})),kt.post(qt+"/mdsgenecount",(async function(t,e){St(t);try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.datasets)throw"no datasets from genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.gene2mutcount)throw"not supported on this dataset";if(!t.query.samples)throw".samples missing";let o,i;o=t.query.selectedMutTypes?t.query.selectedMutTypes.join("+"):"total",i=t.query.nGenes?t.query.nGenes:15;const s=`WITH\n\tfiltered AS (\n\t\tSELECT gene, ${o} AS total FROM genecount\n\t\tWHERE sample IN (${JSON.stringify(t.query.samples).replace(/[[\]\"]/g,"").split(",").map((t=>"'"+t+"'")).join(",")})\n\t)\n\tSELECT gene, SUM(total) AS count\n\tFROM filtered\n\tGROUP BY gene\n\tORDER BY count DESC\n\tLIMIT ${i}`,a=r.gene2mutcount.db.prepare(s).all(),l=[];for(const t of a){const e=n.genedb.getCoordByGene.get(t.gene);e&&(e.gene=t.gene,e.count=t.count,delete e.name,l.push(e))}e.send({genes:l})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/mds2",tt.handle_request(yt)),kt.post(qt+"/mdsexpressionrank",(function(t,e){let n,i,s,a=new Set;Promise.resolve().then((()=>{if(!t.query.rglst)throw"rglst missing";if(t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>1e7)throw"Zoom in below 10 Mb to show expression rank";if(!t.query.sample)throw"sample missing";if(t.query.iscustom){if(n=yt[t.query.genome],!n)throw"invalid genome";if(!t.query.file&&!t.query.url)throw"no file or url for expression data";i={},s={file:t.query.file,url:t.query.url,indexURL:t.query.indexURL}}else{const[e,r,o,a]=Rt(t.query);if(e)throw e;if(n=r,i=o,s=a,!s.samples)throw"total samples missing from server config";if(-1==s.samples.indexOf(t.query.sample))throw{nodata:1}}if(s.viewrangeupperlimit&&t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>s.viewrangeupperlimit)throw"zoom in under "+k.bplen(s.viewrangeupperlimit)+" to view data";if(t.query.levelkey){if(!t.query.levelvalue)throw"levelvalue is required when levelkey is used";if(!i.cohort\|\|!i.cohort.annotation)throw".cohort.annotation missing from dataset"}if(!s.file){if(!s.url)throw"file or url missing";return x.cache_index(s.url,s.indexURL)}})).then((e=>{const n=[];for(const l of t.query.rglst)n.push(new Promise(((n,c)=>{const f=m(vt,[s.file?u.join(o.tpmasterdir,s.file):s.url,l.chr+":"+l.start+"-"+l.stop],{cwd:e}),d=_.createInterface({input:f.stdout}),h=new Map;d.on("line",(e=>{const n=e.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],s=Number.parseInt(n[1]),l=Number.parseInt(n[2]);if(r.sample==t.query.sample)return h.has(r.gene)\|\|h.set(r.gene,{chr:o,start:s,stop:l,allvalues:[]}),h.get(r.gene).thisvalue=r.value,void(r.ase&&(h.get(r.gene).ase=r.ase));if(t.query.attributes){const e=i.cohort.annotation[r.sample];if(!e)return;for(const n of t.query.attributes)if(n.k&&n.kvalue&&n.kvalue!=e[n.k])return}a.add(r.sample),h.has(r.gene)\|\|h.set(r.gene,{chr:o,start:s,stop:l,allvalues:[]}),h.get(r.gene).allvalues.push({value:r.value})}));const p=[];f.stderr.on("data",(t=>p.push(t))),f.on("close",(t=>{const e=p.join("");e&&!r(e)&&c({message:e}),n(h)}))})));return Promise.all(n)})).then((t=>{const n=[];for(const e of t)for(const[t,r]of e)null!=r.thisvalue&&(r.allvalues.sort(((t,e)=>t.value-e.value)),r.rank=Vt(r.thisvalue,r.allvalues),delete r.allvalues,r.gene=t,n.push(r));e.send({result:n,samplecount:a.size})})).catch((t=>{t.stack&&console.log(t),t.nodata?e.send({nodata:1}):e.send({error:t.message?t.message:t})}))})),kt.post(qt+"/mdsgeneboxplot",st(yt)),kt.post(qt+"/mdsgenevalueonesample",(async function(t,e){const n=t.query;try{if(!n.sample)throw".sample missing";if(!n.genes)throw".genes[] missing";let r,i,s;if(t.query.iscustom){if(r=yt[n.genome],!r)throw"invalid genome";if(!n.file&&!n.url)throw"no file or url for expression data";i={},s={file:n.file,url:n.url,indexURL:n.indexURL}}else{const[t,e,o,a]=Rt(n);if(t)throw t;r=e,i=o,s=a}const a=s.file?null:await x.cache_index(s.url,s.indexURL),l={};let c=!0;for(const t of n.genes){let e;await x.get_lines_bigfile({args:[s.file?u.join(o.tpmasterdir,s.file):s.url,t.chr+":"+t.start+"-"+t.stop],dir:a,callback:r=>{const o=r.split("\t");if(!o[3])return;const i=JSON.parse(o[3]);i.gene==t.gene&&i.sample==n.sample&&(e=i.value)}}),Number.isFinite(e)&&(l[t.gene]=e,c=!1)}c?e.send({nodata:1}):e.send({result:l})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/vcf",(async function(t,e){try{const[n,r,o]=ce(t);if(n)throw n;const i=o?await x.cache_index(r,t.query.indexURL):null;if(!t.query.rglst)throw"rglst missing";const s=[];for(const e of t.query.rglst)await x.get_lines_bigfile({args:[r,e.chr+":"+e.start+"-"+e.stop],dir:i,callback:t=>s.push(t)});e.send({linestr:s.join("\n")})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.get(qt+"/vcfheader",(async function(t,e){try{if(!t.query.genome)throw"genome missing";const n=yt[t.query.genome];if(!n)throw"invalid genome";const[r,o,i]=ce(t);if(r)throw r;const s=i?await x.cache_index(o,t.query.indexURL):null;e.send({metastr:(await x.get_header_tabix(o,s)).join("\n"),nochr:await x.tabix_is_nochr(o,s,n)})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/translategm",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=t.query.gm;if(!r)throw"missing gm{}";if(!r.chr)throw"gm.chr missing";if(!r.start)throw"gm.start missing";if(!Number.isInteger(r.start))throw"gm.start not integer";if(!r.stop)throw"gm.stop missing";if(!Number.isInteger(r.stop))throw"gm.stop not integer";const o=await x.get_fasta(n,r.chr+":"+(r.start+1)+"-"+r.stop),i=k.fasta2gmframecheck(r,o);e.send({frame:i})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.get(qt+"/hicstat",(async function(t,e){St(t);try{const[n,r,o]=ce(t);if(n)throw"illegal file name";o\|\|await x.file_is_readable(r);const i=await it(r,o);e.send({out:i})}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.post(qt+"/hicdata",(function(t,e){const[n,r,o]=ce(t);if(n)return void e.send({error:"illegal file name"});const i=[t.query.nmeth\|\|"NONE",r,t.query.pos1,t.query.pos2,t.query.isfrag?"FRAG":"BP",t.query.resolution],s=m(wt,i),a=_.createInterface({input:s.stdout}),l=[],c=[];let u=0,f=0;a.on("line",(e=>{const n=e.split("\t");if(3!=n.length)return void u++;const r=Number.parseInt(n[0]),o=Number.parseInt(n[1]),i=Number.parseFloat(n[2]);Number.isNaN(r)\|\|Number.isNaN(o)\|\|Number.isNaN(i)?f++:null!=t.query.mincutoff&&i<=t.query.mincutoff\|\|l.push([r,o,i])})),s.stderr.on("data",(t=>c.push(t))),s.on("close",(()=>{const t=c.join("");return t?e.send({error:t}):u?e.send({error:u+" lines have other than 3 fields"}):f?e.send({error:f+" lines have non-numerical values in any of the 3 fields"}):void e.send({items:l})}))})),kt.post(qt+"/samplematrix",(function(t,e){Promise.resolve().then((()=>{const e=yt[t.query.genome];if(!e)throw"invalid genome";let n,r;if(t.query.iscustom){if(!t.query.querykey2tracks)throw"querykey2tracks{} missing for custom dataset";n={queries:{}};for(const e in t.query.querykey2tracks){const r=t.query.querykey2tracks[e];if(!r.type)throw'missing "type" for a data track';if(r.type==k.tkt.mdsvcf){const r=t.query.querykey2tracks[e];r.type=k.mdsvcftype.vcf,n.queries[e]={type:k.tkt.mdsvcf,info:r.info,tracks:[r]}}else if(r.type==k.tkt.mdssvcnv)n.queries[e]=r;else{if(r.type!=k.tkt.mdsexpressionrank)throw"unknown type of data track: "+r.type;n.queries[e]=r}}}else{if(!e.datasets)throw"genome is not equipped with datasets";if(!t.query.dslabel)throw"dslabel missing";if(n=e.datasets[t.query.dslabel],!n)throw"invalid dslabel";if(!n.queries)throw"dataset is not equipped with queries"}if(t.query.sampleset)r=new Set(t.query.sampleset);else if(t.query.limitsamplebyeitherannotation){if(!n.cohort)throw"limitsamplebyeitherannotation but no cohort in ds";if(!n.cohort.annotation)throw"limitsamplebyeitherannotation but no cohort.annotation in ds";r=new Set;for(const e in n.cohort.annotation){const o=n.cohort.annotation[e];for(const n of t.query.limitsamplebyeitherannotation)if(o[n.key]==n.value){r.add(e);break}}}const o=[];for(const e of t.query.features){let t,i=[];if(e.querykey){if(!n.queries)throw"using querykey for a feature but no ds.queries";if(t=n.queries[e.querykey],!t)throw"unknown dsquery by key "+e.querykey}else if(e.querykeylst){if(!n.queries)throw"using querykeylst for a feature but no ds.queries";for(const t of e.querykeylst){const e=n.queries[t];if(!e)throw'unknown key "'+t+'" from querykeylst';i.push(e)}if(0==i.length)throw"no valid keys in querykeylst"}else if(!e.issampleattribute)throw"unknown way to query a feature";if(e.isgenevalue){const[i,s]=Qt(e,n,t,r);if(i)throw"error with isgenevalue: "+i;o.push(s)}else if(e.iscnv){const[i,s]=Kt(e,n,t,r);if(i)throw"error with iscnv: "+i;o.push(s)}else if(e.isloh){const[i,s]=Xt(e,n,t,r);if(i)throw"error with isloh: "+i;o.push(s)}else if(e.isvcf){const[i,s]=oe(e,n,t,r);if(i)throw"error with isvcf: "+i;o.push(s)}else if(e.isitd){const[i,s]=te(e,n,t,r);if(i)throw"error with isitd: "+i;o.push(s)}else if(e.issvfusion){const[i,s]=ee(e,n,t,r);if(i)throw"error with issvfusion: "+i;o.push(s)}else if(e.issvcnv){const[i,s]=ne(e,n,t,r);if(i)throw"error with issvcnv: "+i;o.push(s)}else if(e.ismutation){const[t,s]=re(e,n,i,r);if(t)throw"error with ismutation: "+t;o.push(s)}else{if(!e.issampleattribute)throw"unknown type of feature";{const[t,i]=Yt(e,n,r);if(t)throw"error with issampleattribute: "+t;o.push(i)}}}return Promise.all(o)})).then((t=>{e.send({results:t})})).catch((t=>{e.send({error:"string"==typeof t?t:t.message}),t.stack&&console.error(t.stack)}))})),kt.get(qt+"/mdssamplescatterplot",(async function(t,e){St(t);try{const n=yt[t.query.genome];if(!n)throw"invalid genome";const r=n.datasets[t.query.dslabel];if(!r)throw"invalid dataset";if(!r.cohort)throw"no cohort for dataset";if(!r.cohort.annotation)throw"cohort.annotation missing for dataset";const o=r.cohort.scatterplot;if(!o)throw"scatterplot not supported for this dataset";const i=[];for(const e in r.cohort.annotation){const n=r.cohort.annotation[e];if(t.query.subsetkey&&n[t.query.subsetkey]!=t.query.subsetvalue)continue;const s=n[o.x.attribute];if(!Number.isFinite(s))continue;const a=n[o.y.attribute];Number.isFinite(a)&&i.push({sample:e,x:s,y:a,s:n})}e.send({colorbyattributes:o.colorbyattributes,colorbygeneexpression:o.colorbygeneexpression,querykey:o.querykey,dots:i,tracks:o.tracks})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/mdssamplesignature",(function(t,e){try{const n=t.query;if(!n.sample)throw".sample missing";const r=yt[n.genome];if(!r)throw"invalid genome";const o=r.datasets[n.dslabel];if(!o)throw"invalid dataset";if(!o.cohort)throw"no cohort for dataset";if(!o.cohort.mutation_signature)throw"no mutation_signature for cohort";const i=[];for(const t in o.cohort.mutation_signature.sets){const e=o.cohort.mutation_signature.sets[t];if(!e.samples)continue;const r=e.samples.map.get(n.sample);if(!r)continue;const s=[];for(const t in e.signatures)r[t]&&s.push({k:t,v:r[t]});s.length&&i.push({key:t,valuename:e.samples.valuename,annotation:s.sort(((t,e)=>e.v-t.v))})}e.send({lst:i})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/mdssurvivalplot",lt(yt)),kt.post(qt+"/fimo",rt.handle_closure(yt)),kt.all(qt+"/termdb",P.handle_request_closure(yt)),kt.all(qt+"/termdb-barsql",D.handle_request_closure(yt)),kt.post(qt+"/singlecell",nt.handle_singlecell_closure(yt)),kt.post(qt+"/massSession",et.save),kt.get(qt+"/massSession",et.get),kt.get(qt+"/isoformbycoord",(async function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!t.query.chr)throw"chr missing";const r=Number(t.query.pos);if(!Number.isInteger(r))throw"pos must be positive integer";const i=n.tracks.find((t=>t.__isgene));i\|\|reject("no gene track");const s=[];await x.get_lines_bigfile({args:[u.join(o.tpmasterdir,i.file),t.query.chr+":"+r+"-"+r],callback:t=>{const e=t.split("\t")[3];if(!e)return;const r=JSON.parse(e);if(!r.isoform)return;const o={isoform:r.isoform},i=n.genedb.getjsonbyisoform.get(r.isoform);i&&(o.name=JSON.parse(i.genemodel).name,o.isdefault=i.isdefault),s.push(o)}}),e.send({lst:s})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/ase",(async function(t,e){const n=t.query,r=3e6,i=5e5;try{const t=yt[n.genome];if(!t)throw"invalid genome";if(!n.samplename)throw"samplename missing";if(!n.chr)throw"no chr";if(!n.start\|\|!n.stop)throw"no start/stop";if(!n.rnabarheight)throw"no rnabarheight";if(!n.dnabarheight)throw"no dnabarheight";if(!Number.isInteger(n.barypad))throw"invalid barypad";if(n.rnamax&&!Number.isFinite(n.rnamax))throw"invalid value for rnamax";if(!n.checkrnabam)throw".checkrnabam{} missing";const s=$t(n.checkrnabam);if(s)throw s;if(n.refcolor\|\|(n.refcolor="blue"),n.altcolor\|\|(n.altcolor="red"),!t.tracks)throw"genome.tracks[] missing";const a=t.tracks.find((t=>t.__isgene));if(!a)throw"no gene track from this genome";await async function(t,e){if(t.rnabamfile)t.rnabamfile=u.join(o.tpmasterdir,t.rnabamfile);else{if(!t.rnabamurl)throw"no file or url for rna bam";t.rnabamurl_dir=await x.cache_index(t.rnabamurl,t.rnabamindexURL\|\|t.rnabamurl+".bai")}if(t.rnabam_nochr=await x.bam_ifnochr(t.rnabamfile\|\|t.rnabamurl,e,t.rnabamurl_dir),t.vcffile)t.vcffile=u.join(o.tpmasterdir,t.vcffile);else{if(!t.vcfurl)throw"no file or url for vcf";t.vcfurl_dir=await x.cache_index(t.vcfurl,t.vcfindexURL)}t.vcf_nochr=await x.tabix_is_nochr(t.vcffile\|\|t.vcfurl,t.vcfurl_dir,e)}(n,t);const l=await Wt(t,a,n.chr,n.start,n.stop),f={};if(n.stop-n.start<r)for(const[t,e]of l){const t={file:n.rnabamfile,url:n.rnabamurl,dir:n.rnabamurl_dir,nochr:n.rnabam_nochr};let r;r=n.rnabamispairedend?await Ft(t,n.chr,e):await Pt(t,n.chr,e),e.fpkm=1e9r/(n.rnabamtotalreadse.exonlength)}else f.fpkmrangelimit=r;const[d,h,p,y]=function(t,e){let n=t.start,r=t.stop;for(const[t,o]of e)n=Math.min(n,o.start),r=Math.max(r,o.stop);const o=t.start,i=t.stop;return[n,r,o,i]}(n,l),v=await async function(t,e,n,r,o){const i=await Ht(t.vcffile\|\|t.vcfurl,t.vcfurl_dir),[s,a,l,c]=q.vcfparsemeta(i);if(c)throw c;const u={info:s,format:a,samples:l},f=await Jt(t.vcffile\|\|t.vcfurl,(t.vcf_nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+o,t.vcfurl_dir),d=[];for(const e of f\|\|[]){const[n,r,o]=q.vcfparseline(e,u);for(const e of r){if(!k.basecolor[e.ref]\|\|!k.basecolor[e.alt])continue;if(!e.sampledata)continue;const n=Ut(e,t.samplename,t.checkrnabam);n&&d.push(n)}}const h=[];for(const t of d)for(const[e,r]of n)if(t.pos>=r.start&&t.pos<=r.stop){h.push(t);break}return h}(n,0,l,d,h);for(const t of v)t.rnacount={nocoverage:1};let b,w;y-p>=i?f.covplotrangelimit=i:(n.rnamax?b=n.rnamax:(b=await async function(t,e,n){let r=0;return await x.get_lines_bigfile({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl\|\|t.rnabamfile],dir:t.rnabamurl_dir,callback:t=>{const e=t.split("\t");if(3!=e.length)return;const n=Number.parseInt(e[2]);Number.isInteger(n)&&(r=Math.max(r,n))}}),r}(n,p,y),f.rnamax=b),w=await async function(t,e,n,r,o){const i=new Map;for(const t of r)t.dnacount.ishet&&t.pos>=e&&t.pos<=n&&i.set(t.pos,t);const s=g(t.widtht.devicePixelRatio,(t.rnabarheight+t.barypad+t.dnabarheight)t.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio);let l,c,u=!1;n-e<=t.width?(u=!0,l=1,c=t.width/(n-e),a.lineWidth=c):(c=1,l=(n-e)/t.width);return await x.get_lines_bigfile({isbam:!0,args:["depth","-r",(t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(e+1)+"-"+(n+1),"-g","DUP",t.rnabamurl\|\|t.rnabamfile],dir:t.rnabamurl_dir,callback:n=>{const r=n.split("\t");if(3!=r.length)return;const s=Number.parseInt(r[1])-1;if(!Number.isInteger(s))return;const f=Number.parseInt(r[2]);if(!Number.isInteger(f))return;const d=t.rnabarheightMath.min(f,o)/o,h=u?(s-e)c:(s-e)/l;a.strokeStyle="#ccc",a.beginPath(),a.moveTo(h+c/2,t.rnabarheight),a.lineTo(h+c/2,t.rnabarheight-d),a.stroke(),a.closePath(),f>o&&(a.strokeStyle="blue",a.beginPath(),a.moveTo(h+c/2,0),a.lineTo(h+c/2,2),a.stroke(),a.closePath());const p=i.get(s);p&&(p.rnacount.h=d)}}),{canvas:s,ctx:a,isbp:u,binpxw:c,binbpsize:l}}(n,p,y,v,b)),f.coveragesrc=await function(t,e,n,r,o,i,s,a){const l=[];for(const n of e)n.dnacount.ishet&&l.push((t.rnabam_nochr?t.chr.replace("chr",""):t.chr)+":"+(n.pos+1)+"-"+(n.pos+1));return new Promise(((n,r)=>{const c=m(_t,["mpileup","-q",t.checkrnabam.rnapileup_q,"-Q",t.checkrnabam.rnapileup_Q,"--no-reference","-a","INFO/AD","-d",999999,"-r",l.join(","),t.rnabamurl\|\|t.rnabamfile],{cwd:t.rnabamurl_dir});_.createInterface({input:c.stdout}).on("line",(t=>{if("#"==t[0])return;const n=Gt(t);if(!n)return;let r;n.pos>=o&&n.pos<=i&&n.DP;const s=e.find((t=>t.pos==n.pos));if(s){s.__x=r;const t=n.allele2count[s.ref]\|\|0,e=n.allele2count[s.alt]\|\|0;t+e>0&&(delete s.rnacount.nocoverage,s.rnacount.ref=t,s.rnacount.alt=e,s.rnacount.f=e/(t+e))}})),c.on("close",(()=>{if(!s)return void n();const{canvas:r,ctx:l,binpxw:c}=s;l.lineWidth=Math.max(3,c);let u=0;for(const n of e)n.dnacount&&(n.pos<o\|\|n.pos>i\|\|(n.__x=t.width(n.pos-o)/(i-o),u=Math.max(u,n.dnacount.ref+n.dnacount.alt)));for(const n of e){if(null==n.__x)continue;n.rnacount.nocoverage\|\|(null==n.rnacount.h&&(n.rnacount.h=t.rnabarheight(n.rnacount.ref+n.rnacount.alt)/a),l.strokeStyle=t.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight),l.lineTo(n.__x+c/2,t.rnabarheight-(1-n.rnacount.f)n.rnacount.h),l.stroke(),l.closePath(),l.strokeStyle=t.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight-(1-n.rnacount.f)n.rnacount.h),l.lineTo(n.__x+c/2,t.rnabarheight-n.rnacount.h),l.stroke(),l.closePath());const e=t.dnabarheight(n.dnacount.ref+n.dnacount.alt)/u;n.dnacount.ishet&&(l.strokeStyle=t.refcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight+t.barypad),l.lineTo(n.__x+c/2,t.rnabarheight+t.barypad+(1-n.dnacount.f)e),l.stroke(),l.closePath(),l.strokeStyle=t.altcolor,l.beginPath(),l.moveTo(n.__x+c/2,t.rnabarheight+t.barypad+(1-n.dnacount.f)e),l.lineTo(n.__x+c/2,t.rnabarheight+t.barypad+e),l.stroke(),l.closePath()),delete n.__x}n(r.toDataURL())}))}))}(n,v,0,0,p,y,w,b),await async function(t,e){if(0==t.length)return;const n=[];for(const r of t)r.rnacount.nocoverage\|\|r.rnacount.ref+r.rnacount.alt<e.checkrnabam.rna_mintotalreads\|\|n.push(r);if(0==n.length)return;const r=await function(t){const e=u.join(o.cachedir,Math.random().toString())+".snp",n=[];for(const e of t)e.rnacount.nocoverage\|\|null!=e.rnacount.ref&&null!=e.rnacount.alt&&n.push(e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt);return new Promise(((t,r)=>{c.writeFile(e,n.join("\n")+"\n",(n=>{n&&r("cannot write"),t(e)}))}))}(n),i=await Zt(r);await function(t,e){return new Promise(((n,r)=>{c.readFile(e,"utf8",((e,o)=>{e&&r("cannot read binom pvalue"),o\|\|n();for(const e of o.trim().split("\n")){const n=e.split("\t"),r=t.find((t=>n[0]==t.pos+"."+t.ref+"."+t.alt));r&&(r.rnacount.pvalue=Number.parseFloat(n[10]))}n()}))}))}(t,i),c.unlink(r,(()=>{})),c.unlink(i,(()=>{}))}(v,n),f.genes=function(t,e,n){const r=[];for(const[o,i]of e){r.push(i);const e=t.filter((t=>t.pos>=i.start&&t.pos<=i.stop));if(0==e.length){i.nosnp=1;continue}i.snps=e;const o=e.filter((t=>null!=t.rnacount.pvalue));if(0==o.length){i.nornasnp=1;continue}const s=o.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let a=null,l=0;for(const t of o)null==a?a=t.rnacount.pvalue:a=t.rnacount.pvalue,t.rnacount.pvalue<=n.checkrnabam.binompvaluecutoff&&l++;i.ase={markers:e.filter((t=>t.dnacount.ishet)).length,ase_markers:l,mean_delta:s/o.length,geometricmean:Math.pow(a,1/o.length)}}return r}(v,l,n);let N=0;for(const t of v)t.dnacount&&t.pos>=p&&t.pos<=y&&(N=Math.max(N,t.dnacount.ref+t.dnacount.alt));f.dnamax=N,e.send(f)}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.post(qt+"/bamnochr",(async function(t,e){const n=t.query;try{const t=yt[n.genome];if(!t)throw"invalid genome";if(n.file)n.file=u.join(o.tpmasterdir,n.file);else{if(!n.url)throw"no bam file or url";n.url_dir=await x.cache_index(n.url,n.indexURL\|\|n.url+".bai")}const r=await x.bam_ifnochr(n.file\|\|n.url,t,n.url_dir);e.send({nochr:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}})),kt.get(qt+"/gene2canonicalisoform",(function(t,e){St(t);try{if(!t.query.gene)throw".gene missing";const n=yt[t.query.genome];if(!n)throw"unknown genome";if(!n.genedb.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const r=n.genedb.get_gene2canonicalisoform.get(t.query.gene);e.send(r)}catch(t){e.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}})),kt.get(qt+"/ideogram",(function(t,e){try{const n=yt[t.query.genome];if(!n)throw"invalid genome";if(!n.genedb.hasIdeogram)throw"ideogram not supported on this genome";if(!t.query.chr)throw".chr missing";const r=n.genedb.getIdeogramByChr.all(t.query.chr);if(!r.length)throw"no ideogram data for this chr";e.send(r)}catch(t){e.send({error:t.message\|\|t})}})),async function(){try{await c.promises.stat(o.tpmasterdir)}catch(t){const e="Error with "+o.tpmasterdir+": "+t.code;if("validate"==process.argv[2])throw e;return void console.log("\n!!! "+e+"\n")}if(function(){if(o.features.skip_checkDependenciesAndVersions)return void console.log("SKIPPED checkDependenciesAndVersions()");const t=["jsonlite","cmprsk","hwde","lmtest"];for(const e of t){const t=p.spawnSync(o.Rscript,["-e",`suppressPackageStartupMessages(library("${e}"))`],{encoding:"utf8"});if(t.stderr.trim())throw t.stderr}{const t=p.execSync(o.samtools+" --version",{encoding:"utf8"}).trim().split("\n"),[e,n]=t[0].split(" ");if("samtools"!=e\|\|!n)throw'cannot run "samtools version"';const[r,i]=n.split(".");if("1"!=r)throw"samtools not 1.";if(Number(i)<10)throw"samtools not >= 1.10"}{const t=p.execSync(o.bcftools+" -v",{encoding:"utf8"}).trim().split("\n"),[e,n]=t[0].split(" ");if("bcftools"!=e\|\|!n)throw'cannot run "bcftools version"';const[r,i]=n.split(".");if("1"!=r)throw"bcftools not 1.";if(Number(i)<10)throw"bcftools not >= 1.10"}}(),null!=o.base_zindex){const t=Number.parseInt(o.base_zindex);if(Number.isNaN(t)\|\|t<=0)throw"base_zindex must be positive integer";o.base_zindex=t}if(o.jwt){if(!o.jwt.secret)throw"jwt.secret missing";if(!o.jwt.permissioncheck)throw"jwt.permissioncheck missing"}if(!o.tpmasterdir)throw".tpmasterdir missing";if(!o.cachedir)throw".cachedir missing";o.cachedir_massSession=await he("massSession"),o.cachedir_massSessionTrash=await he("massSessionTrash"),o.cache_snpgt={dir:await he("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},o.cachedir_bam=await he("bam"),o.cachedir_genome=await he("genome"),o.cachedir_ssid=await he("ssid"),o.commonOverrides&&k.applyOverrides(o.commonOverrides);if(!o.genomes)throw".genomes[] missing";if(!Array.isArray(o.genomes))throw".genomes[] not array";for(const t of o.genomes){if(!t.name)throw".name missing from a genome: "+JSON.stringify(t);if(!t.file)throw".file missing from genome "+t.name;const e=u.join(process.cwd(),t.file),n=require(c.existsSync(e)?e:t.file),r=n.default\|\|n;if(yt[t.name]=r,!r.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==r.genomefile\|\|(r.genomefile=u.join(o.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,r]of e.entries())if(t)if("object"==typeof r)for(const e in r)t[e]=r[e];else{if("string"==typeof t[r]){e[n+1]&&(t[r]=e[n+1]);break}t=t[r]}}}o.defaultgenome&&yt[o.defaultgenome]&&(yt[o.defaultgenome].isdefault=!0);for(const t in yt){const n=yt[t];if(!n.majorchr)throw t+": majorchr missing";if(!n.defaultcoord)throw t+": defaultcoord missing";if(await x.get_fasta(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]+/),r={},o=[];for(let n=0;n<e.length;n+=2){const i=e[n],s=Number.parseInt(e[n+1]);if(Number.isNaN(s))throw t+" majorchr invalid chr size for "+i+" ("+e[n+1]+")";r[i]=s,o.push(i)}n.majorchr=r,n.majorchrorder=o}n.chrlookup={};for(const t in n.majorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.majorchr[t],major:!0};if(n.minorchr){if("string"==typeof n.minorchr){const e=n.minorchr.trim().split(/[\s\t\n]+/),r={};for(let n=0;n<e.length;n+=2){const o=Number.parseInt(e[n+1]);if(Number.isNaN(o))throw t+" minorchr invalid chr size for "+e[n]+" ("+e[n+1]+")";r[e[n]]=o}n.minorchr=r}for(const t in n.minorchr)n.chrlookup[t.toUpperCase()]={name:t,len:n.minorchr[t]}}if(n.genedb){if(!n.genedb.dbfile)throw t+": .genedb.dbfile missing";try{console.log("Connecting",n.genedb.dbfile),n.genedb.db=x.connect_db(n.genedb.dbfile)}catch(t){throw`Cannot connect genedb: ${n.genedb.dbfile}: ${t}`}n.genedb.getnamebynameorisoform=n.genedb.db.prepare("select name from genes where name=? or isoform=?"),n.genedb.getnamebyisoform=n.genedb.db.prepare("select distinct name from genes where isoform=?"),n.genedb.getjsonbyname=n.genedb.db.prepare("select isdefault,genemodel from genes where name=?"),n.genedb.getjsonbyisoform=n.genedb.db.prepare("select isdefault,genemodel from genes where isoform=?"),n.genedb.getnameslike=n.genedb.db.prepare("select distinct name from genes where name like ? limit 20");const e=ht(n.genedb.db);e.has("genealias")&&(n.genedb.getNameByAlias=n.genedb.db.prepare("select name from genealias where alias=?"),n.genedb.tableSize=n.genedb.db.prepare("select count() from genealias where alias=?")),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 ${t}`).get().size)}if(n.termdbs)for(const r in n.termdbs)dt(n.termdbs[r],e.features),console.log(`${r} 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 x.validate_tabixfile(u.join(o.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=x.connect_db(n.proteindomain.dbfile)}catch(t){throw"Error with "+n.proteindomain.dbfile+": "+t}n.proteindomain.getbyisoform=e.prepare(n.proteindomain.statement)}if(n.snp){if(!n.snp.bigbedfile)throw t+".snp: missing bigBed file";n.snp.bigbedfile=u.join(o.tpmasterdir,n.snp.bigbedfile),await x.file_is_readable(n.snp.bigbedfile)}if(n.clinvarVCF){if(!n.clinvarVCF.file)throw t+".clinvarVCF: VCF file missing";n.clinvarVCF.file=u.join(o.tpmasterdir,n.clinvarVCF.file);try{await x.validate_tabixfile(n.clinvarVCF.file)}catch(t){throw"Error with "+n.clinvarVCF.file+": "+t}if(!n.clinvarVCF.infokey)throw t+".clinvarVCF.infokey missing";if(!n.clinvarVCF.categories)throw t+".clinvarVCF.categories{} missing";{const e=p.execSync(vt+" -H "+n.clinvarVCF.file,{encoding:"utf8"}).trim();if(!e)throw t+".clinvarVCF: no meta/header lines";const[r,o,i,s]=q.vcfparsemeta(e.split("\n"));if(s)throw t+".clinvarVCF: error parsing vcf meta: "+s.join("\n");if(!r[n.clinvarVCF.infokey])throw t+".clinvarVCF: unknown INFO key for "+n.clinvarVCF.infokey;n.clinvarVCF.info=r,n.clinvarVCF.format=o}{const e=p.execSync(vt+" -l "+n.clinvarVCF.file,{encoding:"utf8"}).trim();if(""==e)throw t+".clinvarVCF: no chr listing";n.clinvarVCF.nochr=k.contigNameNoChr(n,e.split("\n"))}}if(n.fimo_motif){if(!n.fimo_motif.db)throw t+".fimo_motif: db file missing";if(n.fimo_motif.db=u.join(o.tpmasterdir,n.fimo_motif.db),n.fimo_motif.annotationfile){const[t,e]=ue(c.readFileSync(u.join(o.tpmasterdir,n.fimo_motif.annotationfile),{encoding:"utf8"}).trim());n.fimo_motif.tf2attr={};for(const t of e)n.fimo_motif.tf2attr[t.Model.split("_")[0]]=t}}if(n.hicenzymefragment){if(!Array.isArray(n.hicenzymefragment))throw"hicenzymefragment should be an array";for(const 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 x.validate_tabixfile(u.join(o.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 e=n.hicdomain.groups[t];if(!e.name)throw".name missing from hicdomain "+t;if(!e.sets)throw".set{} missing from hicdomain "+t;for(const n in e.sets){const r=e.sets[n];if(!r.name)throw".name missing from hicdomain "+t+" > "+n;if(!r.file)throw".file missing from hicdomain "+t+" > "+n;r.file=u.join(o.tpmasterdir,r.file);try{await x.validate_tabixfile(r.file)}catch(t){throw"Error with "+r.file+": "+t}}}}if(n.rawdslst){n.datasets={};for(const e of n.rawdslst){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 r=u.join(process.cwd(),e.jsfile),o=require(c.existsSync(r)?r:e.jsfile),i="function"==typeof o?o(k):"function"==typeof(null==o?void 0:o.default)?o.default(k):o.default\|\|o;if(Q(i,e),i.noHandleOnClient=e.noHandleOnClient,i.label=e.name,i.genomename=t,n.datasets[i.label]=i,i.isMds3)try{await X.init(i,n,e,kt,qt)}catch(t){throw t.stack&&console.log(t.stack),"Error with mds3 dataset "+i.label+": "+t}else if(i.isMds)try{await me(i,n,e)}catch(t){throw"Error with mds dataset "+i.label+": "+t}else de(i,n)}fe(),delete n.rawdslst}}}().then((async()=>{if(console.log(`\n${new Date} ${o.commitHash\|\|""}`),console.log("\nValidation succeeded.\n"),"validate"!=process.argv[2])if("phewas-precompute"!=process.argv[2])await async function(){try{if(o.preListenScript){const{cmd:t,args:e}=o.preListenScript,n=p.spawnSync(t,e,{encoding:"utf-8"});if(n.stderr.trim())throw n.stderr.trim();console.log(n.stdout)}o.appEnable&&o.appEnable.forEach((t=>kt.enable(t)));const t=o.port,e=`STANDBY AT PORT ${t}`;if(o.ssl){const n={key:c.readFileSync(o.ssl.key),cert:c.readFileSync(o.ssl.cert)},r=await l.createServer(n,kt);return r.listen(t,"0.0.0.0",(()=>{console.log(`HTTPS ${e}`)})),r}{const n=await a.createServer(kt);return n.listen(t,"0.0.0.0",(()=>{process.send&&process.send("ready"),console.log(e)})),n}}catch(t){throw t}}();else{const t=process.argv[3],e=process.argv[4],n=yt[t];if(!n)throw"invalid genome name: "+t;const r=n.datasets[e];if(!r)throw"invalid dataset: "+e;at.do_precompute(r)}else console.log("You may now run the server.")})).catch((t=>{let e=1;if(!c.existsSync(o.tpmasterdir)){const t=o.maintenance\|\|{};if("start"in t&&"stop"in t&&"tpErrorCode"in t){const n=+new Date(t.start),r=+new Date(t.stop),o=+new Date;n<=o&&o<=r&&(e=t.tpErrorCode)}}t.stack&&console.log(t.stack),e?console.error("\n!!!\n"+t+"\n\n"):console.log("\n!!!\n"+t+"\n\n"),process.exit(e)})),e.log=St,e.searchSNP=Ct,e.boxplot_getvalue=function(t){const e=t.length;if(e<5)return{out:t};const n=t[Math.floor(e/2)].value,r=t[Math.floor(e/4)].value,o=t[Math.floor(3e/4)].value,i=t[Math.floor(.05e)].value,s=t[Math.floor(.95e)].value,a=(t[Math.floor(.01e)].value,o-r);let l,c;if(0==a)l=0,c=0;else{const n=t.findIndex((t=>t.value>r-1.5a));l=t[-1==n?0:n].value;const i=t.findIndex((t=>t.value>o+1.5a));c=t[-1==i?e-1:i-1].value}const u=t.filter((t=>t.value<r-1.5a\|\|t.value>o+1.5a));return{w1:l,w2:c,p05:i,p25:r,p50:n,p75:o,p95:s,iqr:a,out:u}};function se(t){delete t.mclasslabel2key,delete t.sample2disease,delete t.patient2ori2sample}const ae=Object.freeze([".bam",".bai",".gz",".tbi",".csi",".bw",".bb"]);function le(t,e=!1,n=!0){if("/"==t[0])return!0;if(t.includes('"')\|\|t.includes("'"))return!0;if(t.includes("\|")\|\|t.includes("&"))return!0;if(t.includes(" "))return!0;if(-1!=t.indexOf(".."))return!0;if(t.match(/(\<script\|script\>)/i))return!0;if(e&&o.whiteListPaths){let e=!0;for(const n of o.whiteListPaths){if(t.startsWith(n)\|\|"!"!=n[0]&&pt(t,n)){e=!1;break}if("!"==n[0]&&!pt(t,n)){e=!0;break}}if(e)return!0}if(n)for(const e of ae)if(e===u.extname(t).toLowerCase())return!0;return!1}function ce(t,e=!0){let n=null,r=!1;if(t.query.file){if(n=t.query.file,le(n,e,!1))return["illegal file path"];n=u.join(o.tpmasterdir,n)}else if(t.query.url){if(n=t.query.url,n.includes(" "))return["url must not contain whitespace"];if(n.includes('"')\|\|n.includes("'"))return["url must not contain single or double quotes"];r=!0}return n?[null,n,r]:["file unspecified"]}function ue(t){const e=t.split(/\r?\n/);if(e.length<=1\|\|!e[0])return[null,[]];const n=e[0].split("\t"),r=[];for(let t=1;t<e.length;t++){if("#"==e[t][0])continue;const o=e[t].split("\t"),i={};for(let t=0;t<n.length;t++){const e=o[t];e&&(i[n[t]]=e)}r.push(i)}return[null,r]}async function fe(){const t=await c.promises.readdir(o.cachedir_massSession);try{t.forEach((async t=>{const e=(await c.promises.stat(u.join(o.cachedir_massSession,t))).birthtime,n=new Date,r=new Date(e),i=o.features.massSessionDuration\|\|30;Math.round((n.getTime()-r.getTime())/864e5)>i&&(await c.promises.copyFile(u.join(o.cachedir_massSession,t),u.join(o.cachedir_massSessionTrash,t)),await c.promises.unlink(u.join(o.cachedir_massSession,t)),console.log("File deleted: ",t,e))}))}catch(t){throw`Error: ${t}`}}function de(t,e){if(t.dbfile)try{console.log("Connecting",t.dbfile),t.newconn=x.connect_db(t.dbfile)}catch(e){throw"Error with "+t.dbfile+": "+e}if(t.snvindel_attributes)for(const e of t.snvindel_attributes)if(e.lst)for(const t of e.lst)t.get=t.get.toString();else e.get=e.get.toString();if(t.cohort){if(t.cohort.levels){if(!Array.isArray(t.cohort.levels))throw"cohort.levels must be array for "+t.genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+t.genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+t.genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+t.genomename+"."+t.label;const e=t.newconn.prepare(t.cohort.fromdb.sql).all();delete t.cohort.fromdb,t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.files){let e=[];for(const n of t.cohort.files){if(!n.file)throw".file missing from one of cohort.files[] for "+t.genomename+"."+t.label;const r=c.readFileSync(u.join(o.tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+t.genomename+"."+t.label;e=[...e,...R.tsvParse(r)]}delete t.cohort.files,t.cohort.raw?t.cohort.raw=[...t.cohort.raw,...e]:t.cohort.raw=e,console.log(e.length+" rows retrieved for "+t.label+" sample annotation")}if(t.cohort.tosampleannotation){if(!t.cohort.tosampleannotation.samplekey)throw".samplekey missing from .cohort.tosampleannotation for "+t.genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+t.genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+t.genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=pe(n,t,e);if(r)throw'Error parsing a query in "'+t.label+'": '+r}if(t.vcfinfofilter){const e=k.validate_vcfinfofilter(t.vcfinfofilter);if(e)throw t.label+": vcfinfofilter error: "+e}if(t.url4variant)for(const e of t.url4variant){if(!e.makelabel)throw"makelabel() missing for one item of url4variant from "+t.label;if(!e.makeurl)throw"makeurl() missing for one item of url4variant from "+t.label;e.makelabel=e.makelabel.toString(),e.makeurl=e.makeurl.toString()}}async function he(t){const e=u.join(o.cachedir,t);try{await c.promises.stat(e)}catch(t){if("ENOENT"!=t.code)throw"error stating dir";try{await c.promises.mkdir(e)}catch(t){throw"cannot make dir"}}return e}function pe(t,e,n){if(!t.name)return".name missing";if(t.dsblocktracklst){if(!Array.isArray(t.dsblocktracklst))return"dsblocktracklst not an array in "+e.label;for(const n of t.dsblocktracklst){if(!n.type)return"missing type for a blocktrack of "+e.label;if(!n.file&&!n.url)return"neither file or url given for a blocktrack of "+e.label}}else if(t.vcffile){const e=p.execSync(vt+" -H "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==e)return"no meta lines in VCF file "+t.vcffile+" of query "+t.name;const[r,i,s,a]=q.vcfparsemeta(e.split("\n"));if(a)return"error parsing VCF meta lines of "+t.vcffile+": "+a.join("; ");t.vcf={vcfid:Math.random().toString(),info:r,format:i,samples:s},t.hlinfo&&(t.vcf.hlinfo=t.hlinfo,delete t.hlinfo),t.infopipejoin&&(t.vcf.infopipejoin=t.infopipejoin,delete t.infopipejoin);const l=p.execSync(vt+" -l "+u.join(o.tpmasterdir,t.vcffile),{encoding:"utf8"}).trim();if(""==l)return"tabix -l found no chromosomes/contigs in "+t.vcffile+" of query "+t.name;t.vcf.nochr=k.contigNameNoChr(n,l.split("\n"));let c=0;if(r)for(const t in r)c++;console.log("Parsed vcf meta from "+t.vcffile+": "+c+" INFO, "+s.length+" sample, "+(t.vcf.nochr?'no "chr"':'has "chr"'))}else{if(!t.makequery)return"do not know how to parse query: "+t.name;if(t.isgeneexpression){if(!t.config)return"config object missing for gene expression query of "+t.name;t.config.maf&&(t.config.maf.get=t.config.maf.get.toString())}}}async function me(t,e,n){if((t.isMds2\|\|t.isMds3\|\|t.isMds)&&Q(t,n),t.assayAvailability){if(!t.assayAvailability.file)throw".assayAvailability.file missing";if(!t.assayAvailability.assays)throw".assayAvailability.assays[] missing";Object.freeze(t.assayAvailability.assays),t.assayAvailability.samples=new Map;for(const e of c.readFileSync(u.join(o.tpmasterdir,t.assayAvailability.file),{encoding:"utf8"}).trim().split("\n")){const[n,r]=e.split("\t");t.assayAvailability.samples.set(n,JSON.parse(r))}console.log(t.assayAvailability.samples.size+" samples with assay availability ("+t.label+")")}if(t.gene2mutcount){if(!t.gene2mutcount.dbfile)throw".gene2mutcount.dbfile missing";try{console.log("Connecting",t.gene2mutcount.dbfile),t.gene2mutcount.db=x.connect_db(t.gene2mutcount.dbfile),console.log("DB connected for "+t.label+": "+t.gene2mutcount.dbfile)}catch(e){throw`Error connecting db at ${t.gene2mutcount.dbfile}`}}if(t.sampleAssayTrack){if(!t.sampleAssayTrack.file)throw".file missing from sampleAssayTrack";t.sampleAssayTrack.samples=new Map;let e=0,n=new Set;for(const r of c.readFileSync(u.join(o.tpmasterdir,t.sampleAssayTrack.file),{encoding:"utf8"}).trim().split("\n")){if(!r)continue;if("#"==r[0])continue;const[o,i,s]=r.split("\t");if(!i\|\|!s)continue;if(!t.sampleAssayTrack.samples.has(o)){if(t.cohort&&t.cohort.annotation&&!t.cohort.annotation[o]){n.add(o);continue}t.sampleAssayTrack.samples.set(o,[])}const a=JSON.parse(s);if(!k.tkt[a.type])throw"invalid type from a sample track: "+s;a.name\|\|(a.name=o+" "+i),a.assayName=i,t.sampleAssayTrack.samples.get(o).push(a),e++}console.log(e+" assay-tracks from "+t.sampleAssayTrack.samples.size+" samples ("+t.label+")"),n.size&&console.log("Error: "+n.size+" samples with assay tracks are unannotated: "+[...n].join(" "))}if(t.singlesamplemutationjson){const e=t.singlesamplemutationjson;if(!e.file)throw".file missing from singlesamplemutationjson";e.samples={};let n=0;for(const t of c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim().split("\n")){if(!t)continue;if("#"==t[0])continue;const[r,o]=t.split("\t");r&&o&&(n++,e.samples[r]=o)}console.log(n+" samples for disco plot")}if(t.cohort&&t.cohort.db&&t.cohort.termdb&&await K.init_db(t,kt,qt),t.cohort&&t.cohort.files){if(!Array.isArray(t.cohort.files))throw".cohort.files is not array";if(!t.cohort.tohash)throw".tohash() missing from cohort";if("function"!=typeof t.cohort.tohash)throw".cohort.tohash is not function";if(!t.cohort.samplenamekey)throw".samplenamekey missing";if(t.cohort.annotation={},t.cohort.mutation_signature){const e=t.cohort.mutation_signature;if(!e.sets)throw".mutation_signature.sets missing";for(const n in e.sets){const r=e.sets[n];if(r.name\|\|(r.name=n),!r.signatures)throw".signatures{} missing from a signature set";if(r.samples){if(!r.samples.file)throw".samples.file missing from a signature set";const[e,n]=ue(c.readFileSync(u.join(o.tpmasterdir,r.samples.file),{encoding:"utf8"}).trim());r.samples.map=new Map;for(const e of n){const n=e[t.cohort.samplenamekey];if(!n)throw t.cohort.samplenamekey+" missing in file "+r.samples.file;r.samples.map.set(n,e);for(const t in r.signatures)if(e[t]){const o=Number.parseFloat(e[t]);if(Number.isNaN(o))throw"mutation signature value is not float: "+e[t]+" from sample "+n;r.samples.skipzero&&0==o?delete e[t]:e[t]=o}}}}}if(t.cohort.attributes){if(!t.cohort.attributes.lst)throw".lst[] missing for cohort.attributes";if(!Array.isArray(t.cohort.attributes.lst))return".cohort.attributes.lst is not array";for(const e of t.cohort.attributes.lst){if(!e.key)throw".key missing from one of the .cohort.attributes.lst[]";if(!e.label)throw".label missing from one of the .cohort.attributes.lst[]";if(!e.values)throw".values{} missing from "+e.label+" of .cohort.attributes.lst";for(const t in e.values)if(!e.values[t].label)throw".label missing from one value of "+e.label+" in .cohort.attributes.lst"}if(t.cohort.attributes.defaulthidden)for(const e in t.cohort.attributes.defaulthidden){const n=t.cohort.attributes.lst.find((t=>t.key==e));if(!n)throw"invalid defaulthidden key: "+e;for(const r in t.cohort.attributes.defaulthidden[e])if(!n.values[r])throw"invalid defaulthidden value "+r+" for "+e}}if(t.cohort.hierarchies){if(!t.cohort.hierarchies.lst)throw".lst[] missing from .cohort.hierarchies";if(!Array.isArray(t.cohort.hierarchies.lst))throw".cohort.hierarchies.lst is not array";for(const e of t.cohort.hierarchies.lst){if(!e.name)throw".name missing from one hierarchy";if(!e.levels)throw".levels[] missing from one hierarchy";if(!Array.isArray(e.levels))throw".levels is not array from one hierarchy";for(const t of e.levels)if(!t.k)throw".k missing from one level in hierarchy "+e.name}}if(t.cohort.sampleAttribute){if(!t.cohort.sampleAttribute.attributes)throw"attributes{} missing from cohort.sampleAttribute";for(const e in t.cohort.sampleAttribute.attributes){const n=t.cohort.sampleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from cohort.sampleAttribute.attributes";if(n.values)for(const t in n.values){const e=n.values[t];if("object"!=typeof e)throw'value "'+t+'" not pointing to {} from sampleAttribute';e.name\|\|(e.name=t)}if(n.showintrack&&!n.isinteger&&!n.isfloat)throw n.label+": .showintrack requires .isinteger or .isfloat"}}if(t.cohort.scatterplot){if(!t.cohort.sampleAttribute)throw".sampleAttribute missing but required for .cohort.scatterplot";const e=t.cohort.scatterplot;if(!e.querykey)throw".querykey missing from .cohort.scatterplot";{if(!t.queries)throw".cohort.scatterplot.querykey in use but ds.queries{} missing";const n=t.queries[e.querykey];if(!n)throw"unknown query by .cohort.scatterplot.querykey: "+e.querykey;if(n.type!=k.tkt.mdssvcnv)throw"type is not "+k.tkt.mdssvcnv+" of the track pointed to by .cohort.scatterplot.querykey"}if(e.colorbygeneexpression){if(!e.colorbygeneexpression.querykey)throw"querykey missing from .cohort.scatterplot.colorbygeneexpression";if(!t.queries)throw".cohort.scatterplot.colorbygeneexpression in use but ds.queries{} missing";const n=t.queries[e.colorbygeneexpression.querykey];if(!n)throw"unknown query by .cohort.scatterplot.colorbygeneexpression.querykey: "+e.colorbygeneexpression.querykey;if(!n.isgenenumeric)throw"isgenenumeric missing from the track pointed to by .cohort.scatterplot.colorbygeneexpression.querykey"}if(e.tracks,!e.x)throw".x missing from .cohort.scatterplot";if(!e.x.attribute)throw".attribute missing from .cohort.scatterplot.x";const n=t.cohort.sampleAttribute.attributes[e.x.attribute];if(!n)throw"scatterplot.x.attribute is not defined in sampleAttribute";if(!n.isfloat)throw'scatterplot.x is not "isfloat"';if(!e.y)throw".y missing from .cohort.scatterplot";if(!e.y.attribute)throw".attribute missing from .cohort.scatterplot.y";const r=t.cohort.sampleAttribute.attributes[e.y.attribute];if(!r)throw"scatterplot.y.attribute is not defined in sampleAttribute";if(!r.isfloat)throw'scatterplot.y is not "isfloat"';if(e.colorbyattributes)for(const n of e.colorbyattributes){if(!n.key)throw".key missing from one of scatterplot.colorbyattributes";const e=t.cohort.sampleAttribute.attributes[n.key];if(!e)throw"unknown attribute by key "+n.key+" from scatterplot.colorbyattributes";n.label=e.label,n.values=e.values}}for(const e of t.cohort.files){if(!e.file)throw".file missing from one of .cohort.files";const[n,r]=ue(c.readFileSync(u.join(o.tpmasterdir,e.file),{encoding:"utf8"}).trim());if(n)throw'cohort annotation file "'+e.file+'": '+n;console.log(t.label+": "+r.length+" samples loaded from annotation file "+e.file),r.forEach((e=>{for(const n in e){let r;t.cohort.sampleAttribute&&(r=t.cohort.sampleAttribute.attributes[n]),r\|\|t.cohort.termdb&&t.cohort.termdb.termjson&&t.cohort.termdb.termjson.map&&(r=t.cohort.termdb.termjson.map.get(n)),r&&(r.isfloat?e[n]=Number.parseFloat(e[n]):r.isinteger&&(e[n]=Number.parseInt(e[n])))}t.cohort.tohash(e,t)}))}if(t.cohort.annorows=Object.values(t.cohort.annotation),console.log(t.label+": total samples from sample table: "+t.cohort.annorows.length),t.cohort.survivalplot){const e=t.cohort.survivalplot;if(!e.plots)throw".plots{} missing from survivalplot";e.init={plottypes:[]};for(const t in e.plots){const n=e.plots[t];if(!n.name)throw".name missing from survivalplot "+t;if(!n.serialtimekey)throw".serialtimekey missing from survivalplot "+t;if(!n.iscensoredkey)throw".iscensoredkey missing from survivalplot "+t;if(!n.timelabel)throw".timelabel missing from survivalplot "+t;n.key=t,e.init.plottypes.push({key:t,name:n.name,timelabel:n.timelabel})}if(e.samplegroupattrlst){e.init.samplegroupings=[];for(const n of e.samplegroupattrlst){if(!n.key)throw".key missing from an attr of samplegroupattrlst for survival";const r=t.cohort.sampleAttribute.attributes[n.key];if(!r)throw'unknown attribute key "'+n.key+'" from survival samplegroupattrlst';const o=new Map;for(const r in t.cohort.annotation){const i=t.cohort.annotation[r],s=i[n.key];if(null==s)continue;let a=!1;for(const t in e.plots)if(null!=i[e.plots[t].serialtimekey]){a=!0;break}a&&(o.has(s)?o.set(s,o.get(s)+1):o.set(s,1))}if(0==o.size)throw'no value found for "'+n.key+'" from survival samplegroupattrlst';const i=[];for(const[t,e]of o)i.push({value:t,count:e});e.init.samplegroupings.push({key:n.key,label:r.label,values:i})}}}}if(t.mutationAttribute){if(!t.mutationAttribute.attributes)throw"attributes{} missing from mutationAttribute";for(const e in t.mutationAttribute.attributes){const n=t.mutationAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from mutationAttribute.attributes";if(!n.appendto_link&&n.values)for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from mutationAttribute.attributes"}}}if(t.alleleAttribute){if(!t.alleleAttribute.attributes)throw"attributes{} missing from alleleAttribute";for(const e in t.alleleAttribute.attributes){const n=t.alleleAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from alleleAttribute.attributes";if(!n.isnumeric){if(!n.values)throw".values{} missing for non-numeric key "+e+" from alleleAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from alleleAttribute.attributes"}}}}if(t.locusAttribute){if(!t.locusAttribute.attributes)throw"attributes{} missing from locusAttribute";for(const e in t.locusAttribute.attributes){const n=t.locusAttribute.attributes[e];if(!n.label)throw".label missing for key "+e+" from locusAttribute.attributes";if(!n.isnumeric&&!n.appendto_link){if(!n.values)throw".values{} missing for non-numeric key "+e+" from locusAttribute.attributes";for(const t in n.values){if(!n.values[t].name)throw".name missing for value "+t+" of key "+e+" from locusAttribute.attributes"}}}}if(t.queries)for(const r in t.queries){if(n.remove_queries&&-1!=n.remove_queries.indexOf(r)){delete t.queries[r];continue}const o=t.queries[r];if(n.hide_queries&&-1!=n.hide_queries.indexOf(r)&&(o.hideforthemoment=1),o.istrack){if(!o.type)throw".type missing for track query "+r;if(o.viewrangeupperlimit&&!Number.isInteger(o.viewrangeupperlimit))throw".viewrangeupperlimit should be integer for track query "+r;if(o.type==k.tkt.mdsjunction){const n=ye(o,t,e);if(n)throw r+" (mdsjunction) error: "+n}else if(o.type==k.tkt.mdscnv){const n=_e(o,t,e);if(n)throw r+" (mdscnv) error: "+n}else if(o.type==k.tkt.mdssvcnv){const n=we(o,t,e);if(n)throw r+" (svcnv) error: "+n}else{if(o.type!=k.tkt.mdsvcf)throw"unknown track type for a query: "+o.type+" "+r;{const n=await ke(o,t,e);if(n)throw r+" (vcf) error: "+n}}ge(o,t)}else{if(!o.isgenenumeric)throw"unknown type of query from "+r;{const n=xe(o,t,e);if(n)throw r+" (genenumeric) error: "+n}}}if(t.track&&await K.init_track(t,e),t.annotationsampleset2matrix){if(!t.cohort)throw"ds.cohort misssing when annotationsampleset2matrix is in use";if(!t.cohort.annotation)throw"ds.cohort.annotation misssing when annotationsampleset2matrix is in use";if(!t.queries)throw"ds.queries misssing when annotationsampleset2matrix is in use";if(!t.annotationsampleset2matrix.key)throw".key STR missing in annotationsampleset2matrix";if(!t.annotationsampleset2matrix.groups)throw".groups{} missing in annotationsampleset2matrix";if("object"!=typeof t.annotationsampleset2matrix.groups)throw"ds.annotationsampleset2matrix.groups{} not an object";for(const e in t.annotationsampleset2matrix.groups){const n=t.annotationsampleset2matrix.groups[e];if(!n.groups\|\|!Array.isArray(n.groups)\|\|0==n.groups.length)throw".groups[] must be nonempty array in "+e;for(const r of n.groups){if(!r.name)throw".name missing from one of .groups[] in "+e;const n=r.matrixconfig;if(!n)throw".matrixconfig missing from one of .groups[] of "+e;if(!n.features)throw".features[] missing from group "+e;if(!Array.isArray(n.features))throw".features[] should be array from group "+e;if(0==n.features.length)throw".features[] zero length from group "+e;for(const r of n.features){if(t.annotationsampleset2matrix.commonfeatureattributes)for(const e in t.annotationsampleset2matrix.commonfeatureattributes)null==r[e]&&(r[e]=t.annotationsampleset2matrix.commonfeatureattributes[e]);if(!r.ismutation)return"unknown feature type from group "+e;if(!r.position)throw"position missing from feature "+JSON.stringify(r)+" from group "+e;if(!r.querykeylst)throw".querykeylst[] missing from ismutation feature from group "+e;if(!Array.isArray(r.querykeylst))throw".querykeylst[] not an array from ismutation feature from group "+e;if(0==r.querykeylst.length)throw".querykeylst[] zero length from ismutation feature from group "+e;for(const n of r.querykeylst)if(!t.queries[n])throw'unknown query key "'+n+'" from ismutation feature of group '+e}if(!n.limitsamplebyeitherannotation)throw".limitsamplebyeitherannotation[] missing from group "+e;if(!Array.isArray(n.limitsamplebyeitherannotation))throw".limitsamplebyeitherannotation[] should be array from group "+e;if(0==n.limitsamplebyeitherannotation.length)throw".limitsamplebyeitherannotation[] zero length from group "+e;for(const t of n.limitsamplebyeitherannotation){if(!t.key)throw"key missing from one of limitsamplebyeitherannotation from group "+e;if(!t.value)throw"value missing from one of limitsamplebyeitherannotation from group "+e}}}delete t.annotationsampleset2matrix.commonfeatureattributes}}function ge(t,e){if(t.groupsamplebyattr){t.groupsamplebyattr.key2group=new Map;for(const n in e.cohort.annotation)Bt(n,[],t.groupsamplebyattr.key2group,[],e,t)}}function ye(t,e,n){if(t.readcountCutoff&&(!Number.isInteger(t.readcountCutoff)\|\|t.readcountCutoff<1))return"readcountCutoff must be positive integer";let r;if(t.file){const[e,n]=ie(t.file);if(e)return"tabix file error: "+e;t.file=n,r=n}else{if(!t.url)return"no file or url given for mdsjunction "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=i.split("\n");if(1!=n.length)return"mdsjunction file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");if(r[5]){t.samples=r.slice(5),t.attributeSummary=ve(t.samples,e),t.hierarchySummary=be(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}if(console.log("(mdsjunction) "+t.name+": "+(t.samples?t.samples.length:0)+" samples, "+(t.nochr?'no "chr"':'has "chr"')),!t.infoFilter)return".infoFilter{} missing";if(!t.infoFilter.lst)return".lst[] missing from .infoFilter";for(const e of t.infoFilter.lst){if(!e.key)return".key missing from one of infoFilter";if(!e.label)return".label missing from one of infoFilter";if(!e.categories)return".categories missing from one of infoFilter";for(const t in e.categories){if(!e.categories[t].label)return".label missing from one category of "+e.label;if(!e.categories[t].color)return".color missing from on category of "+e.label}if(e.hiddenCategories){for(const t in e.hiddenCategories)if(!e.categories[t])return"invalid hidden key "+t+" of "+e.label}else e.hiddenCategories={}}if(!t.singlejunctionsummary)return".singlejunctionsummary missing but is currently required from "+t.name;if(t.singlejunctionsummary.readcountboxplotpercohort){if(!t.singlejunctionsummary.readcountboxplotpercohort.groups)return".groups[] missing from query.singlejunctionsummary.readcountboxplotpercohort for "+t.name;for(const e of t.singlejunctionsummary.readcountboxplotpercohort.groups){if(!e.key)return".key missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups";if(!e.label)return".label missing from one group of query.singlejunctionsummary.readcountboxplotpercohort.groups"}}}function ve(t,e){if(!(e.cohort&&e.cohort.annotation&&e.cohort.attributes&&t))return;const n={};for(const r of e.cohort.attributes.lst){const o={};for(const t in r.values)o[t]=0;for(const n of t){const t=e.cohort.annotation[n];if(!t)continue;const i=t[r.key];null!=i&&(i in o&&o[i]++)}n[r.key]=o}return n}function be(t,e){if(!e.cohort\|\|!e.cohort.annotation\|\|!e.cohort.hierarchies\|\|0==t.length)return;const n=[];for(const r of t){const t=e.cohort.annotation[r];t&&n.push(t)}const r={};for(const t of e.cohort.hierarchies.lst){const e=y(n,t.levels),o=E()(e);o.sum((t=>t.value));const i={};o.eachBefore((t=>{i[t.id]=t.value})),r[t.name]=i}return r}function _e(t,e,n){let r;if(t.file){const[e,n]=ie(t.file);if(e)return"tabix file error: "+e;r=n}else{if(!t.url)return"no file or url given for (mdscnv) "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=i.split("\n");if(1!=n.length)return"mdscnv file has multiple header lines (begin with #), but should have just 1";const r=n[0].split("\t");t.samples=r.slice(5),t.attributeSummary=ve(t.samples,e),t.hierarchySummary=be(t.samples,e);for(const e in t.hierarchySummary){let n=0;for(const r in t.hierarchySummary[e])n++;console.log(n+" "+e+" hierarchy levels for "+t.name)}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}console.log("("+t.type+") "+t.name+": 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i=t.diff_score_plotwidth/(r-o),s=ri-oi,a=p(st.devicePixelRatio,e.canvasheightt.devicePixelRatio),l=a.getContext("2d");t.devicePixelRatio>1&&l.scale(t.devicePixelRatio,t.devicePixelRatio);const c=n.map((t=>t.__tempscore)),u=e.canvasheight/c.length;let f=0;const d=e.stackspace/e.canvasheight;for(const t of c){let e=0;for(const n of t)"alt0"==n?l.fillStyle=Y:"ref"==n?l.fillStyle=nt:"alt1"==n?l.fillStyle=Q:"alt2"==n?l.fillStyle=K:"alt3"==n?l.fillStyle=X:"alt4"==n?l.fillStyle=tt:"alt5"==n&&(l.fillStyle=et),l.fillRect(ie,fu,i,u-du),e+=1;f+=1}return{height:e.canvasheight,width:s,src:a.toDataURL(),read_height:u}}function xt(t,e,n,r){for(const o of n)for(const n of o.segments)if(!(n.ridx!=t\|\|Math.max(n.segstart,e.start)>Math.min(n.segstop,e.stop)))for(const t of n.boxes)if(e.ntwidth>=1){if(("S"==t.opr\|\|"X"==t.opr)&&t.s)for(let e=0;e<t.s.length;e++){const n=t.start+e,o=r.find((t=>t.position==n));if(!o)continue;const i=t.s[e];o[i]=1+(o[i]\|\|0),"S"==t.opr&&o.total++}}else if("S"==t.opr){const 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c=m(k,["-i","-","-t","DNA","--outfmt=clu","--wrap=5000","--maxnumseq="+(e+1),"--maxseqlen=1000"]),u=[],d=[];f.from(t).pipe(c.stdin),c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>d.push(t))),c.on("error",(t=>{console.log("stderr (clustalo):",d),l(t)})),c.on("close",(t=>{let e=0;const c=[],f={final_read_align:[],qual_r:[],qual_g:[],qual_b:[]};let d=0;for(const t of u.toString().split("\n"))if(t.includes("seq ")){let n=0,l="",u=0,h="";0!=e&&a?h=r.split("\n")[e-1].split(","):a\|\|(h=r.split("\n")[e].split(","));let p="",m="",g="";for(const r of t.replace("seq ",""))if(","!=r){if("-"!=r){if(n+=1,l+=r,0==e&&a)c.push(r);else if(r==c[u]&&a\|\|!a){const t=S(h[n-1]/ft).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}else if(r!=c[u]&&a){const t=E(h[n-1]/ft).replace("rgb(","").replace(")","").split(",");p+=t[0]+",",m+=t[1]+",",g+=t[2]+","}}else n>0&&n<t.replace(/-/g,"").replace(/,/g,"").replace("seq 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n=["view",e.file];e.gdc_case_id\|\|n.push((e.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop),await d.get_lines_bigfile({isbam:!0,args:n,dir:e.dir,callback:(n,r)=>{if(!(1024&n.split("\t")[1]&&e.drop_pcrduplicates)){if(e.downsample){const t=e.downsample;if(t.pointer++,t.pointer>=t.keep&&t.pointer<t.keep+t.skip)return;t.pointer>=t.keep+t.skip&&(t.pointer=0)}t.lines.push(n)}}})}async function At(t,e){const n=[],r=["depth","-r",(t.nochr?e.chr.replace("chr",""):e.chr)+":"+(e.start+1)+"-"+e.stop,"-g","DUP",t.file\|\|t.url];if(t.drop_pcrduplicates&&(r.push("-G"),r.push("0x400")),await d.get_lines_bigfile({isbam:!0,args:r,dir:t.dir,callback:t=>{const r=t.split("\t"),o=Number.parseInt(r[1])-1,i=Number.parseInt(r[2]);if(e.ntwidth>=1)return void n.push({position:o,total:i});const s=Math.floor((o-e.start)e.ntwidth);n[s]\|\|(n[s]={position:o,sum:0,count:0}),n[s].sum+=i,n[s].count++}}),e.ntwidth<1)for(const t of n)t&&(t.total=t.sum/t.count,delete t.sum,delete t.count);return n}async function Mt(t,e){for(const t of e.regions)t.lines.length>0&&t.ntwidth>=st&&(t.to_checkmismatch=!0,t.referenceseq=await Et(e.genome,t.chr+":"+(t.start+1)+"-"+t.stop));for(const n of t)for(const t of n.segments){const n=e.regions[t.ridx];if(!n.to_checkmismatch)continue;const r=[];for(const e of t.boxes)null!=e.cidx&&"M"==e.opr&&(e.s=t.seq.substr(e.cidx,e.len),Ft(r,n,e,e.s));r.length&&t.boxes.push(...r)}for(const t of e.regions)delete t.to_checkmismatch,delete t.referenceseq}function Tt(t,e){if(!t.asPaired){const n=[];for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=Ct(i,o,t);e&&n.push({x1:e.x1,x2:e.x2,__tempscore:e.tempscore,segments:[e]})}}return n}const n=new Map;for(let r=0;r<t.regions.length;r++){const o=t.regions[r];for(const i of e.templates){i.ridx=r;const e=Ct(i,o,t);if(!e\|\|!e.qname)continue;const s=n.get(e.qname);s?(s.segments.push(e),s.x2=Math.max(s.x2,e.x2)):n.set(e.qname,{x1:Math.max(e.x1,o.x),x2:Math.min(e.x2,o.x+o.width),__tempscore:e.tempscore,segments:[e]})}}return[...n.values()]}function Ct(t,e,n){const{sam_info:r,tempscore:o,ridx:i,keepallboxes:s,keepmatepos:a,keepunmappedread:l}=t,c=r.trim().split("\t");if(c.length<11)return;const u=c[0],f=c[1],d=Number.parseInt(c[3]),h=c[5],p=c[6],m=c[7],g=Number.parseInt(c[8]),y=c[9],v=c[10];if(Number.isNaN(d)\|\|d<=0)return;const b=d-1,_={qname:u,segstart:b,segstart_original:b,segstop:b,boxes:[],forward:!(16&f),ridx:i,seq:y,qual:v,cigarstr:h,tlen:g,flag:f,tempscore:o};if(function(t,e,n,r,o,i){const s=t.flag;if(!(1&s))return;64&s?t.isfirst=!0:128&s&&(t.islast=!0);if("="!=e&&""!=e&&e!=r.chr)return t.rnext=e,void(t.pnext=n);if(8&s)return void(t.discord_unmapped2=!0);32&s&&!(16&s)&&64&s\|\|16&s&&!(32&s)&&128&s\|\|16&s&&!(32&s)&&64&s\|\|32&s&&!(16&s)&&128&s\|\|(t.discord_orientation=!0,o&&(16&s?32&s?t.discord_orientation_direction="R1R2":n>i&&(t.discord_orientation_direction="R1F2"):32&s?n<i&&(t.discord_orientation_direction="R1F2"):t.discord_orientation_direction="F1F2")),2&s\|\|(t.discord_wrong_insertsize=!0,o&&(t.pnext=n))}(_,p,m,e,a,d),4&f)return l?(_.boxes.push({opr:h,start:b,len:y.length,cidx:0,qual:v}),_.discord_unmapped1=!0,_):void 0;if(""!=h){let t=b,r=0,o=0;for(let n=0;n<h.length;n++){const i=h[n];if(i.match(/[0-9]/))continue;const a=Number.parseInt(h.substring(r,n));if("H"!=i)if("N"==i\|\|"P"==i\|\|"D"==i\|\|(o+=a),r=n+1,"="!=i&&"M"!=i)if("I"!=i)if("N"!=i&&"D"!=i)if("X"!=i)if("S"!=i){if("P"!=i)console.log("unknown cigar: "+i);else if(s\|\|t>e.start&&t<e.stop){const e={opr:"P",start:t,len:a,cidx:o-a};_.boxes.push(e)}}else{const n={opr:i,start:t,len:a,cidx:o-a};0==_.boxes.length?(n.start-=a,(s\|\|Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push(n)):_.boxes.push(n)}else{if(s\|\|Math.max(t,e.start)<Math.min(t+a-1,e.stop)){const e={opr:i,start:t,len:a,cidx:o-a};_.boxes.push(e)}t+=a}else(t>=e.start&&t<=e.stop\|\|t+a-1>=e.start&&t+a-1<=e.stop\|\|s)&&_.boxes.push({opr:i,start:t,len:a}),t+=a;else(s\|\|t>e.start&&t<e.stop)&&ae.ntwidth>=rt&&_.boxes.push({opr:"I",start:t,len:a,cidx:o-a});else(s\|\|Math.max(t,e.start)<=Math.min(t+a-1,e.stop))&&_.boxes.push({opr:i,start:t,len:a,cidx:o-a}),t+=a;else _.boxes.push({opr:i,start:t,len:a,cidx:o-a}),r=n+1}if(0==_.boxes.length)return void(n&&n.readcount_skipped++);_.segstop=t,_.x1=e.x+e.scale(_.boxes[0].start),_.x2=e.x+e.scale((w=_.boxes,Math.max(...w.map((t=>t.start+t.len)))))}var w;return _}async function jt(t,e,n){const[r,o]=function(t,e){let n=(e.groups.length>1?pt/2:pt)/t;return 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r)n.x1<i.x1&&n.x2<i.x1?t.push(n):e.push(n);n=[...t,...o,...e]}for(const r of n){let n=r.segments[0].ridx,o=null;if(!e.variant)for(let i=0;i<t.stacks.length;i++){if(r.x2==e.regions[n].x+e.regions[n].width&&t.stacks[i]<r.x1){o=i,t.stacks[i]=r.x2;break}if(t.stacks[i]+e.stacksegspacing<r.x1){o=i,t.stacks[i]=r.x2;break}}null==o&&(o=t.stacks.length,t.stacks[o]=r.x2),r.y=o}}else{n.sort(((t,e)=>t.x1-e.x1)),t.stacks=[];for(let r=0;r<e.regions.length;r++)for(const o of n)if(o.segments[0].ridx==r){let n=null;if(!e.variant&&!e.sv)for(let i=0;i<t.stacks.length;i++)if(t.stacks[i]+e.stacksegspacing<o.x1&&t.stacks[i]+e.stacksegspacing<e.regions[r].x+e.regions[r].width){n=i,t.stacks[i]=o.x2;break}null==n&&(n=t.stacks.length,t.stacks[n]=o.x2),o.y=n}}return n=function(t,e,n){if(!t.partstack)return e;const r=e.filter((e=>e.y>=t.partstack.start&&e.y<=t.partstack.stop));r.forEach((e=>e.y-=t.partstack.start)),e=r,t.stacks=[];for(let e=t.partstack.start;e<=t.partstack.stop;e++)t.stacks.push(0);return 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o={qname:e.segments[0].qname,x1:Math.max(t.x,e.x1),x2:Math.min(e.x2,t.x+t.width),y1:e.y,y2:e.y+(e.height\|\|n.stackheight),start:Math.min(...e.segments.map((t=>t.segstart))),stop:Math.max(...e.segments.map((t=>t.segstop)))},e.segments[0].isfirst&&(o.isfirst=!0),e.segments[0].islast&&(o.islast=!0);n.returntemplatebox.push(o)}for(let o=0;o<e.segments.length;o++){const i=e.segments[o],s=n.regions[i.ridx];if(s.width=n.widths[i.ridx],0==o){Dt(t,i,e.y,n,r);continue}const a=e.segments[o-1],l=n.regions[a.ridx];if(l.width=n.widths[a.ridx],a.x2<=i.x1\|\|e.segments[0].ridx!=e.segments[1].ridx){Dt(t,i,e.y,n,r);const o=Math.floor(e.y+n.stackheight/2)+.5;if(t.strokeStyle=n.stackheight<=2?J:q,t.setLineDash([5,3]),t.beginPath(),l.x==s.x?(t.moveTo(a.x2,o),t.lineTo(i.x1,o)):l.x<a.x2&&i.x1<s.width&&(t.moveTo(Math.min(a.x2,l.width),o),t.lineTo(Math.max(i.x1,s.x),o)),t.stroke(),n.overlapRP_hlline){const r=a.boxes.reduce(((t,e)=>t.start+t.len>e.start+e.len?t:e));if(r.start+r.len==i.boxes[0].start){t.strokeStyle=H,t.setLineDash([]),t.beginPath();const r=Math.floor(i.x1)+.5;t.moveTo(r,e.y),t.lineTo(r,e.y+n.stackheight),t.stroke()}}}else if(n.overlapRP_multirows){if(Dt(t,i,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=H,t.setLineDash([]),t.beginPath(),l.x<=a.x2&&i.x1<=s.width&&(t.moveTo(Math.max(i.x1,s.x),r),t.lineTo(Math.min(a.x2,l.width),r)),t.stroke()}}else Dt(t,i,e.y,n,r)}null!=e.__tempscore&&x.features.indel_read_alignment_scores&&(t.fillStyle="blue",t.font=n.stackheight+"pt Arial",t.fillText(e.__tempscore,r.regions[0].width-100,e.y+n.stackheight/2))}function Dt(t,e,n,r,o){const i=r.regions[e.ridx];i.width=r.widths[e.ridx];for(const o of e.boxes){const s=i.x+i.scale(o.start);if("P"!=o.opr&&"H"!=o.opr&&"I"!=o.opr)if("D"!=o.opr&&"N"!=o.opr)if(""!=o.opr){if("X"!=o.opr&&"S"!=o.opr){if("M"!=o.opr&&"="!=o.opr)throw"unknown opr at 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o.qual?e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q:i.to_printnt?t.fillStyle="white":e.rnext?t.fillStyle=A:e.discord_orientation?t.fillStyle=D:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q,s+o.leni.ntwidth+dt<i.width&&s<i.width&&i.x<s+dt?t.fillRect(s,n,o.leni.ntwidth+dt,r.stackheight):s+o.leni.ntwidth+dt<i.width&&i.x>=s?t.fillRect(i.x,n,o.leni.ntwidth+dt+s-i.x,r.stackheight):s+o.leni.ntwidth+dt>=i.width&&i.x<s?t.fillRect(s,n,i.width-s,r.stackheight):s+o.leni.ntwidth+dt>=i.width&&i.x>=s&&t.fillRect(i.x,n,i.width-s,r.stackheight);if(i.to_printnt){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial",o.qual?t.fillStyle="white":t.fillStyle="black";for(let e=0;e<o.s.length;e++)s+i.ntwidth(e+.5)<i.width&&s<i.width&&i.x<=s+i.ntwidth(e+.5)&&t.fillText(o.s[e],s+i.ntwidth(e+.5),n+r.stackheight/2)}}else if(i.to_qual&&o.qual){i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial");let e=s;for(let s=0;s<o.qual.length;s++){const a=o.qual[s]/ft;t.fillStyle="S"==o.opr?P(a):E(a),e+i.ntwidth+dt<i.x+i.width&&i.x<=e?t.fillRect(e,n,i.ntwidth+dt,r.stackheight):e<i.x+i.width&&e+i.ntwidth+dt>=i.x+i.width&&i.x<=e?t.fillRect(e,n,i.width+i.x-e,r.stackheight):e<=i.x&&e+i.ntwidth+dt>i.x&&t.fillRect(i.x,n,i.ntwidth+dt+e-i.x,r.stackheight),i.to_printnt&&(o.qual?t.fillStyle="white":t.fillStyle="black",e+i.ntwidth/2<i.width&&e<i.width&&i.x<=e+i.ntwidth/2&&t.fillText(o.s[s],e+i.ntwidth/2,n+r.stackheight/2)),e+=i.ntwidth}}else if(t.fillStyle="S"==o.opr?R:j,s+o.leni.ntwidth+dt<i.width&&i.x<s?t.fillRect(s,n,o.leni.ntwidth+dt,r.stackheight):s+o.leni.ntwidth+dt<i.width&&i.x>=s?t.fillRect(i.x,n,o.leni.ntwidth+dt+s-i.x,r.stackheight):s+o.leni.ntwidth+dt<=i.width&&i.x<s&&t.fillRect(s,n,i.width-s,r.stackheight),i.to_printnt&&!o.qual){t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt 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i=Math.ceil(e.x2+dt);i<=r.width+n.stackheight/2&&(t.fillStyle="white",t.beginPath(),t.moveTo(i-n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i-n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i-n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}else{const i=e.x1;i>=r.x&&(t.fillStyle="white",t.beginPath(),t.moveTo(i+n.stackheight/2,o),t.lineTo(i,o),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o),t.closePath(),t.fill(),t.beginPath(),t.moveTo(i+n.stackheight/2,o+n.stackheight),t.lineTo(i,o+n.stackheight),t.lineTo(i,o+n.stackheight/2),t.lineTo(i+n.stackheight/2,o+n.stackheight),t.closePath(),t.fill())}}(t,e,r,i,n),e.rnext&&(i.to_qual\|\|e.x2-e.x1>=20&&r.stackheight>=7&&(t.font=Math.min(G,Math.max(U,r.stackheight-4))+"pt Arial",t.fillStyle="white",t.fillText((o.nochr?"chr":"")+e.rnext,(e.x1+e.x2)/2,n+r.stackheight/2,e.x2-e.x1)))}function zt(t,e,n,r){for(const[t,n]of e.regions.entries()){if(!n.to_printnt)continue;const e=new Set;for(const o of r)for(const r of o.segments){if(r.ridx!=t)continue;const o=r.boxes.filter((t=>"I"==t.opr));if(o.length)for(const t of o)e.add(n.x+n.scale(t.start))}}for(const n of r)for(const r of n.segments){const o=e.regions[r.ridx],i=r.boxes.filter((t=>"I"==t.opr));if(i.length){t.font=Math.max(G,e.stackheight-2)+"pt Arial";for(const s of i){const i=o.x+o.scale(s.start);s.qual?t.fillStyle=Z(s.qual.reduce(((t,e)=>t+e),0)/s.qual.length/ft):t.fillStyle=B;const a=1==s.s.length?s.s:s.s.length;t.fillText(a,i,n.y+e.stackheight(r.on2ndrow\|\|0)+e.stackheight/2)}}}}async function Bt(t,e,n){const r=It(t.qual),o=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)for(let n=0;n<e.len;n++){t.seq[e.cidx+n];o.push('<td style="background:'+S(r[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>")}const i=[];i.push('<li><span style="background:'+F+';color:white">This segment in template is unmapped</span></li>'),1&t.flag&&i.push("<li>Template has multiple segments</li>"),2&t.flag&&i.push("<li>Each segment properly aligned</li>"),16&t.flag&&i.push("<li>Reverse complemented</li>"),32&t.flag&&i.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&i.push("<li>This is the first segment in the template</li>"),128&t.flag&&i.push("<li>This is the last segment in the template</li>"),256&t.flag&&i.push("<li>Secondary alignment</li>"),512&t.flag&&i.push("<li>Not passing filters</li>"),1024&t.flag&&i.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&i.push("<li>Supplementary alignment</li>");let s={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center">\n\t\t\t <tr style="color:white">${o.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE</span>: ${Math.abs(t.seq.length)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${i.join("")}</ul>`};return t.discord_unmapped2&&(s.unmapped_mate=!0),s}async function $t(t,e,n){const r=t.boxes[0].start,o=t.boxes[t.boxes.length-1],i=o.start+o.len,s=await Et(e,n.chr+":"+(r+1)+"-"+i),a=It(t.qual),l=["<td>Reference</td>"],c=['<td style="color:black;text-align:left">Read</td>'];for(const e of t.boxes)if("H"!=e.opr)if("I"!=e.opr)if("D"!=e.opr&&"N"!=e.opr)if("S"!=e.opr)if("M"!=e.opr&&"="!=e.opr&&"X"!=e.opr&&""!=e.opr);else for(let n=0;n<e.len;n++){const o=s[e.start-r+n],i=t.seq[e.cidx+n];l.push("<td>"+o+"</td>"),""==t.qual?c.push('<td style="color:black;background:'+(o.toUpperCase()==i.toUpperCase()?S:E)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+(o.toUpperCase()==i.toUpperCase()?S:E)(a[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>")}else for(let n=0;n<e.len;n++)l.push("<td>"+s[e.start-r+n]+"</td>"),""==t.qual?c.push('<td style="background:'+P(1)+'">'+t.seq[e.cidx+n]+"</td>"):c.push('<td style="background:'+P(a[e.cidx+n]/ft)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=vt)l.push('<td style="font-size:.8em;opacity:.5;white-space:nowrap">'+e.len+" bp</td>"),c.push('<td style="color:black;white-space:nowrap">-----------</td>');else for(let t=0;t<e.len;t++)l.push("<td>"+s[e.start-r+t]+"</td>"),c.push('<td style="color:black">-</td>');else for(let n=e.cidx;n<e.cidx+e.len;n++)l.push("<td>-</td>"),""==t.qual?c.push('<td style="color:'+B+';background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:'+B+";background:"+S(a[n]/ft)+'">'+t.seq[n]+"</td>");let u=0,f=0,d=[],h=[],p=0;for(const e of t.boxes)u=f,f+=e.len,"S"==e.opr&&(p=1,d.push(u),h.push(f));const m=[];t.rnext&&m.push('<li>Next segment on <span style="background:'+A+'">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:'+T+';color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:'+D+';color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:'+T+';color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:'+D+';color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:'+F+';color:white">Other segment in template is unmapped</span></li>'),1&t.flag&&m.push("<li>Template has multiple segments</li>"),2&t.flag&&m.push("<li>Each segment properly aligned</li>"),16&t.flag&&m.push("<li>Reverse complemented</li>"),32&t.flag&&m.push("<li>Next segment in the template is reverse complemented</li>"),64&t.flag&&m.push("<li>This is the first segment in the template</li>"),128&t.flag&&m.push("<li>This is the last segment in the template</li>"),256&t.flag&&m.push("<li>Secondary alignment</li>"),512&t.flag&&m.push("<li>Not passing filters</li>"),1024&t.flag&&m.push("<li>PCR or optical duplicate</li>"),2048&t.flag&&m.push("<li>Supplementary alignment</li>");let g={seq:t.seq,alignment:`<table style="border-spacing:0px;border-collapse:separate;text-align:center;font-family:courier">\n\t\t\t <tr style="opacity:.6">${l.join("")}</tr>\n\t\t\t <tr style="color:white">${c.join("")}</tr>\n\t\t\t</table>`,info:`<div style='margin-top:10px'>\n\t\t\t<span style="opacity:.5;font-size:.7em">CHR</span>: ${n.chr.replace("chr","")},\n\t\t\t<span style="opacity:.5;font-size:.7em">START</span>: ${t.segstart_original+1},\n\t\t\t<span style="opacity:.5;font-size:.7em">STOP</span>: ${i},\n\t\t\t<span style="opacity:.5;font-size:.7em">READ LENGTH</span>: ${t.seq.length} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">TEMPLATE LENGTH</span>: ${Math.abs(t.tlen)} bp,\n\t\t\t<span style="opacity:.5;font-size:.7em">CIGAR</span>: ${t.cigarstr}\n\t\t\t<span style="opacity:.5;font-size:.7em">FLAG</span>: ${t.flag}\n\t\t\t<span style="opacity:.5;font-size:.7em">NAME: ${t.qname}</span>\n\t\t </div>\n\t\t <ul style='padding-left:15px'>${m.join("")}</ul>`,start_readpos:r+1,boxes:t.boxes,readpanel_DN_maxlength:vt};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function Zt(t){const e=i.createHmac("md5",_t),n=[t.get("X-Auth-Token")\|\|t.cookies.sessionid,t.query.gdcFileUUID,t.query.gdcFilePosition];return e.update(n.join("")).digest("hex")+".bam"}async function Gt(t){const e=t.query.regions;if(!Array.isArray(e)\|\|0==e.length)throw"req.query.regions[] not non-empty array";const n=[];for(const r of e){const e=await Ut(r.chr,r.start,r.stop,t.get("X-Auth-Token"),t.query.gdcFileUUID,Zt(t),t.cookies.sessionid);n.push({filesize:e})}return n}async function Ut(t,e,n,r,o,i,s){const f={compression:!1};s?f.Cookie=`sessionid=${s}`:f["X-Auth-Token"]=r;const h=c.join(x.cachedir_bam,i),p=bt+"/slicing/view/"+o+"?region="+t+":"+e+"-"+n;try{if(await d.file_not_exist(h)&&(await l(a.stream(p,{method:"GET",headers:f}),u.createWriteStream(h)),await d.file_not_exist(h)))throw"BAM file slice is not found after downloading";const t=h+".bai";if(await d.file_not_exist(t)&&(await async function(t){await d.get_lines_bigfile({isbam:!0,args:["index",t],callback:()=>{}})}(h),await d.file_not_exist(t)))throw"index file is missing after indexing";const e=await u.promises.stat(h);return _(e.size,!0)}catch(t){throw t.stack&&console.log(t.stack),"Error with BAM slicing: "+(t.message\|\|t)}}t.exports=t=>async(e,n)=>{try{if(delete e.query.isFileSlice,e.query.gdcFileUUID){const t=e.cookies.sessionid,n=e.get("X-Auth-Token");if(!n&&!t)throw"GDC token or sessionid missing";await w(e.query.gdcFileUUID,n,t),e.query.file=Zt(e),e.query.isFileSlice=!0}if(e.query.downloadgdc)return void n.send(await Gt(e));if(e.query.clientdownloadgdcslice){if(!e.query.file\|\|!e.query.isFileSlice)throw"invalid query";const t=c.join(x.cachedir_bam,e.query.file),r=await u.promises.readFile(t);return n.writeHead(200,{"Content-Type":"application/octet-stream","Content-Disposition":"attachment; filename=gdc.bam","Content-Length":r.length}),void n.end(Buffer.from(r,"binary"))}if(!e.query.genome)throw".genome missing";const o=t[e.query.genome];if(!o)throw"invalid genome";if(e.query.getread)return void n.send(await async function(t,e){if(!e.query.chr)throw".chr missing";if(!e.query.qname)throw".qname missing";if(e.query.qname=decodeURIComponent(e.query.qname),!e.query.start)throw".start missing";if(!e.query.stop)throw".stop missing";const n={chr:e.query.chr,start:Number(e.query.start),stop:Number(e.query.stop),scale:()=>{},ntwidth:10};if(!Number.isInteger(n.start))throw".start not integer";if(!Number.isInteger(n.stop))throw".stop not integer";const o=await async function(t,e){let n,o,i,s,a,l,u,f,p;if(t.query.isFileSlice)a=c.join(x.cachedir_bam,t.query.file),await kt(t,a);else{if([s,a,l]=r.fileurl(t),s)throw s;i=l?await d.cache_index(a,t.query.indexURL\|\|a+".bai"):null}if(t.query.unknownorder&&(u=Number(t.query.readstart),f=Number(t.query.readstop),Number.isNaN(u)\|\|Number.isNaN(f)))throw"readstart/stop not provided for read with unknown order";if(await d.get_lines_bigfile({isbam:!0,args:["view",a,(t.query.nochr?t.query.chr.replace("chr",""):t.query.chr)+":"+e.start+"-"+e.stop],dir:i,callback:(r,i)=>{if(r.split("\t")[0]!=t.query.qname)return;const s=Ct({sam_info:r,keepallboxes:!0,keepmatepos:!0,keepunmappedread:!0},e);if(s&&(!t.query.show_unmapped\|\|!s.discord_unmapped2))if(t.query.show_unmapped&&t.query.getfirst){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.show_unmapped&&t.query.getlast){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getfirst){if(s.isfirst)return i.kill(),void(p=[s])}else if(t.query.getlast){if(s.islast)return i.kill(),void(p=[s])}else if(t.query.unknownorder){if(s.segstart==u&&s.segstop==f)return i.kill(),void(p=[s])}else if(s.isfirst?n=s:s.islast&&(o=s),n&&o)return i.kill(),void(p=[n,o])}}),p){if(t.query.altseqs){const e={query_seq:p[0].seq,refseqs:t.query.refseqs,altseqs:t.query.altseqs,cigar_seq:p[0].cigarstr,start_position:p[0].segstart,ref_positions:t.query.ref_positions,refalleles:t.query.refalleles,altalleles:t.query.altalleles},n=(await h("align",JSON.stringify(e))).split("\n");let r;for(let t of n)t.includes("Final_output:")?r=JSON.parse(t.replace("Final_output:","")):console.log(t);p.alignments=r}return p}p=[],n&&p.push(n);o&&p.push(o);return p.length?p:null}(e,n);if(!o){if(e.query.show_unmapped)throw"mate not found";throw"read not found"}const i=[];for(const n of o)n.discord_unmapped1?i.push(await Bt(n,t,e.query)):i.push(await $t(n,t,e.query));o.alignments&&(i[0].alignments=o.alignments);return{lst:i}}(o,e));const i=x.debugmode?new Date:null,s=await async function(t,e){let n;if(e.query.isFileSlice)n={genome:t,file:c.join(x.cachedir_bam,e.query.file),asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},await kt(e,n.file);else{const[o,i,s]=r.fileurl(e);if(o)throw o;n={genome:t,file:i,asPaired:e.query.asPaired,getcolorscale:e.query.getcolorscale,devicePixelRatio:e.query.devicePixelRatio?Number(e.query.devicePixelRatio):1},s&&(n.dir=await d.cache_index(i,e.query.indexURL\|\|i+".bai"))}if(e.query.pileupheight&&(n.pileupheight=Number(e.query.pileupheight),Number.isNaN(n.pileupheight)))throw".pileupheight is not integer";e.query.drop_pcrduplicates&&(n.drop_pcrduplicates=!0);if(e.query.variant){n.diff_score_plotwidth=Number(e.query.diff_score_plotwidth),e.query.max_diff_score&&(n.max_diff_score=Number(e.query.max_diff_score),n.min_diff_score=Number(e.query.min_diff_score));const t=e.query.variant.split(".");if(n.strictness=e.query.strictness,!Number.isInteger(t.length%4))throw"invalid variant, not chr.pos.ref.alt";n.alleleAlreadyUpdated=e.query.alleleAlreadyUpdated,n.alleleAlreadyUpdated&&(n.altseqs=e.query.altseqs,n.refseqs=e.query.refseqs,n.altalleles=e.query.altalleles,n.refalleles=e.query.refalleles,n.leftflankseqs=e.query.leftflankseqs,n.rightflankseqs=e.query.rightflankseqs,n.ref_positions=e.query.ref_positions);const r=t.length/4,o=[];for(let e=0;e<r;e++)o.push({chr:t[4e],pos:Number(t[4e+1]),ref:t[4e+2],alt:t[4e+3]});if(n.variant=o,e.query.alignOneGroup&&(n.alignOneGroup=e.query.alignOneGroup),Number.isNaN(n.variant.pos))throw"variant pos not integer"}else if(e.query.sv){const t=e.query.sv.split(".");if(t.length<6)throw"invalid sv, not chrA.posA.chrB.posB";if(n.sv={chrA:t[0],startA:Number(t[1]),strandA:Number(t[2]),chrB:t[3],startB:Number(t[4]),strandB:Number(t[5])},Number.isNaN(n.sv.startA))throw"sv.startA not integer";if(Number.isNaN(n.sv.startB))throw"sv.startB not integer"}if(Number.isFinite(Number(e.query.stackstart))){if(!e.query.stackstop)throw".stackstop missing";if(n.partstack={start:Number(e.query.stackstart),stop:Number(e.query.stackstop)},Number.isNaN(n.partstack.start))throw".stackstart not integer";if(Number.isNaN(n.partstack.stop))throw".stackstop not integer";if(!e.query.grouptype)throw".grouptype required for partstack";n.grouptype=e.query.grouptype}e.query.gdc\|\|(e.query.nochr?n.nochr="string"==typeof e.query.nochr?JSON.parse(e.query.nochr):e.query.nochr:n.nochr=await d.bam_ifnochr(n.file,t,n.dir));if(n.regions=e.query.regions,!Array.isArray(n.regions)\|\|0==n.regions.length)throw"q.regions[] not non-empty array";let o=0;for(const t of n.regions){if(!t.chr)throw".chr missing from a region";if(!Number.isInteger(t.start))throw".start not integer of a region";if(!Number.isInteger(t.stop))throw".stop not integer of a region";t.scale=e=>Math.ceil(t.width(e-t.start)/(t.stop-t.start)),t.ntwidth=t.width/(t.stop-t.start),o=Math.max(o,t.ntwidth)}return n.stacksegspacing=Math.max(2,5o),n.readcount_skipped=0,n}(o,e);n.send(await async function(t){await async function(t){if(t.variant){let e=0,n=0,r=0,o=t.variant[0].pos,i=t.variant[0].pos+Math.max(t.variant[0].ref.length,t.variant[0].alt.length);for(const s of t.variant){const t=Math.abs(s.pos-Math.max(s.ref.length,s.alt.length));t>e&&(e=t,n=r),o>s.pos&&(o=s.pos),i<s.pos+Math.max(s.ref.length,s.alt.length)&&(i=s.pos+Math.max(s.ref.length,s.alt.length)),r+=1}e=Math.floor(1.5Math.max(t.variant[n].ref.length,t.variant[n].alt.length));const s={chr:t.variant[0].chr,start:o-e,stop:i+e};return await Nt(t,[s]),await St(s,t),void(t.regions[0].lines=s.lines)}await Nt(t,t.regions);for(const e of t.regions)await St(e,t)}(t),t.totalnumreads=t.regions.reduce(((t,e)=>t+e.lines.length),0);const e={nochr:t.nochr,count:{r:t.totalnumreads},groups:[]};t.read_limit_reached&&(e.count.read_limit_reached=t.read_limit_reached);t.canvaswidth=t.regions[t.regions.length-1].x+t.regions[t.regions.length-1].width;{const n=await async function(t){const e=[],n=[];let r=0;for(const o of t.regions){for(const t of o.lines)e.push({sam_info:t,tempscore:""});r=o.x+o.width,n.push(r)}if(0==e.length)return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]};if(t.variant){if(1==t.regions.length)return await y(t,e,n);console.log("Indel pipeline works only in single region. Please check!")}if(t.sv&&t.regions.length>1)return async function(t,e,n){const r=v.make_type2group(e),o=[];for(let t=0;t<e.regions.length;t++){const n=e.regions[t],r=(await d.get_fasta(e.genome,n.chr+":"+n.start+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase(),i=[];for(const e of n.lines)i.push({sam_info:e,tempscore:"",ridx:t});const s={refseq:r,start:n.start,stop:n.stop,entries:i};0==t?(s.chr=e.sv.chrA,s.pos=e.sv.startA):1==t?(s.chr=e.sv.chrB,s.pos=e.sv.startB):console.log("More than two regions, please check"),o.push(s)}const i=new Date,s=(await h("sv",JSON.stringify(o))).split("\n"),a=new Date;let l,c;console.log("Time taken to run rust SV pipeline:",a-i,"ms");for(let t of s)t.includes("multi_region_templates:")?l=JSON.parse(t.replace("multi_region_templates:","")):t.includes("single_region_templates:")&&(c=JSON.parse(t.replace("single_region_templates:","")));if(!e.grouptype\|\|"support_sv"==e.grouptype)for(const t of l)r[v.type_supportsv].templates.push(t);if(!e.grouptype\|\|"support_ref"==e.grouptype)for(const t of c)r[v.type_supportref].templates.push(t);const u=[];for(const t in r){const e=r[t];0!=e.templates.length&&(t==v.type_supportsv?1==e.templates.length?e.messages.push({isheader:!0,t:e.templates.length+" read supporting SV/fusion"}):e.messages.push({isheader:!0,t:e.templates.length+" reads supporting SV/fusion"}):t==v.type_supportref&&e.messages.push({isheader:!0,t:e.templates.length+" reads supporting reference allele"}),e.widths=n,u.push(e))}return{groups:u}}(0,t,n);return{groups:[{type:v.type_all,regions:v.duplicateRegions(t.regions),templates:e,messages:[],partstack:t.partstack,widths:n}]}}(t);t.groups=n.groups,t.variant&&(e.ref_alleles=n.refalleles,e.alt_alleles=n.altalleles,e.allele_positions=n.ref_positions,e.strand_probability=n.strand_probability,e.alternate_forward_count=n.alternate_forward_count,e.reference_forward_count=n.reference_forward_count,e.alternate_reverse_count=n.alternate_reverse_count,e.reference_reverse_count=n.reference_reverse_count,1==n.strand_significance&&(e.strand_significance=!0),t.alleleAlreadyUpdated\|\|(e.refseqs=n.refseqs,e.altseqs=n.altseqs,e.leftflankseqs=n.leftflankseqs,e.rightflankseqs=n.rightflankseqs,e.ref_positions=n.ref_positions,e.refalleles=n.refalleles,e.altalleles=n.altalleles)),Number.isFinite(t.max_diff_score)&&t.variant?(e.max_diff_score=t.max_diff_score,e.min_diff_score=t.min_diff_score):Number.isFinite(n.max_diff_score)&&(e.max_diff_score=n.max_diff_score,e.min_diff_score=n.min_diff_score),n.refalleleerror&&(e.refalleleerror=n.refalleleerror)}if(0==e.count.r)throw"No reads in view range.";if(t.alignOneGroup){const e=t.groups.find((e=>e.type==t.alignOneGroup));if(!e)throw"cannot find group for realignment";let n=Tt(t,e);return n=Ot(e,t,n),await async function(t,e,n){let r;if(e.variant)if("support_ref"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await qt(n,o,t.partstack.start,t.partstack.stop,e.refseqs[0]):await qt(n,o,0,0,e.refseqs[0])}else if("support_no"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await qt(n,o,t.partstack.start,t.partstack.stop):await qt(n,o)}else if("support_amb"==t.type)console.log("Realignment of reads in ambiguous group is not currently implemented");else if(t.type.includes("support_alt")){for(let o=0;o<e.variant.length;o++)if(t.type=="support_alt"+o.toString()){let i=e.leftflankseqs[o].length;r=t.partstack?await qt(n,i,t.partstack.start,t.partstack.stop,e.altseqs[o]):await qt(n,i,0,0,e.altseqs[o])}}else console.log("Unaccounted group, please check");return{alignmentData:r}}(e,t,n)}let n=[];for(const r of t.groups){let o=Tt(t,r);o=Ot(r,t,o),await jt(r,t,o),await Mt(o,t),Rt(r,o,t);const i={type:r.type,width:t.canvaswidth,height:r.canvasheight,stackheight:r.stackheight,stackcount:r.stacks.length,allowpartstack:r.allowpartstack,templatebox:r.returntemplatebox,count:{r:o.reduce(((t,e)=>t+e.segments.length),0)}},s=p(t.canvaswidtht.devicePixelRatio,r.canvasheightt.devicePixelRatio),a=s.getContext("2d");t.devicePixelRatio>1&&a.scale(t.devicePixelRatio,t.devicePixelRatio),a.textAlign="center",a.textBaseline="middle",i.messages=r.messages,i.messagerowheights=0;for(const e of o)Lt(a,e,r,t);zt(a,r,t,o),t.asPaired&&(i.count.t=o.length),t.variant&&(i.diff_scores_img=await wt(t,r,o,e.max_diff_score,e.min_diff_score),"support_alt0"==i.type?i.group_color=Y:"support_alt1"==i.type?i.group_color=Q:"support_alt2"==i.type?i.group_color=K:"support_alt3"==i.type?i.group_color=X:"support_alt4"==i.type?i.group_color=tt:"support_alt5"==i.type?i.group_color=et:"support_ref"==i.type&&(i.group_color=nt)),i.src=s.toDataURL(),e.groups.push(i),n=[...n,...o]}t.readcount_skipped&&(e.count.skipped=t.readcount_skipped);t.getcolorscale&&(e.colorscale=function(t){const e=160,n=20,r=1,o=12,i=5,s=100,a=4,l=s+e+10,c=2o+i+a+4(n+r),u=p(t.devicePixelRatiol,t.devicePixelRatioc),f=u.getContext("2d");t.devicePixelRatio>1&&f.scale(t.devicePixelRatio,t.devicePixelRatio);f.fillStyle="black",f.font=o+"pt Arial",f.textAlign="center",f.fillText("Base quality",s+e/2,o);let d=2o+i;function h(t,r,o){const i=s,a=f.createLinearGradient(i,o,i+e,o);a.addColorStop(0,r),a.addColorStop(1,t),f.fillStyle=a,f.fillRect(i,o,e,n)}return f.strokeStyle="black",f.beginPath(),f.moveTo(s,d),f.lineTo(s,d+a),f.moveTo(s+e/4,d),f.lineTo(s+e/4,d+a),f.moveTo(s+e/2,d),f.lineTo(s+e/2,d+a),f.moveTo(s+3e/4,d),f.lineTo(s+3e/4,d+a),f.moveTo(s+e,d),f.lineTo(s+e,d+a),f.closePath(),f.stroke(),f.fillText(40,s,d),f.fillText(30,s+e/4,d),f.fillText(20,s+e/2,d),f.fillText(10,s+3e/4,d),f.fillText(0,s+e,d),f.textAlign="left",f.textBaseline="middle",d+=a,f.fillText("Match",0,d+n/2),h(N,q,d),d+=n+r,f.fillStyle="black",f.fillText("Mismatch",0,d+n/2),h(O,j,d),d+=n+r,f.fillStyle="black",f.fillText("Softclip",0,d+n/2),h(I,R,d),d+=n+r,f.fillStyle="black",f.fillText("Insertion",0,d+n/2),h($,B,d),{width:l,height:c,src:u.toDataURL()}}(t));if(!t.partstack)if(0==e.count.r);else{if(!t.pileupheight)throw"pileupheight missing";e.pileup_data=await async function(t,e){const n=p(t.canvaswidtht.devicePixelRatio,t.pileupheightt.devicePixelRatio),r=n.getContext("2d");t.devicePixelRatio>1&&r.scale(t.devicePixelRatio,t.devicePixelRatio);const o=[];let i=0;for(const[n,r]of t.regions.entries()){o[n]=await At(t,r),xt(n,r,e,o[n]);for(const t of o[n])t&&(i=Math.max(i,t.total))}for(const[e,n]of t.regions.entries()){const s=t.pileupheight/i;for(const i of o[e]){if(!i)continue;const e=(i.position-n.start)n.ntwidth+n.x,o=n.ntwidth>=1?e:Math.floor(e),a=Math.max(1,n.ntwidth);{r.fillStyle=V;const e=i.totals;r.fillRect(o,t.pileupheight-e,a,e)}let l=0;if(i.A){r.fillStyle=b.A;const e=i.As;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.C){r.fillStyle=b.C;const e=i.Cs;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.G){r.fillStyle=b.G;const e=i.Gs;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.T){r.fillStyle=b.T;const e=i.Ts;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.softclip){r.fillStyle=R;const e=i.softclips;r.fillRect(o,t.pileupheight-l-e,a,e)}}}return{width:t.canvaswidth,maxValue:i,src:n.toDataURL()}}(t,n)}return e}(s)),x.debugmode&&console.log("bam.js time ms",new Date-i)}catch(t){n.send({error:t.message\|\|t}),t.stack&&console.log(t.stack)}}},8953:(t,e,n)=>{"use strict";n.d(e,{Y:()=>s});n(8171).jStat,n(1017),n(9699).features;const r=n(3856),o=n(1271).run_rust,i=(n(2081).spawn,n(2781).Readable,n(4521),n(2384));n(7147),n(334).clustalo;async function s(t,e,n){const s=t.regions[0].lines[0].split("\t")[9].length;let a=!1,l=[],c=[],u=[],f=[],d=[],h=[],p=[];if(t.alleleAlreadyUpdated)l=t.leftflankseqs,c=t.rightflankseqs,h=t.refseqs,p=t.altseqs,u=t.refalleles,f=t.altalleles,d=t.ref_positions,0!=h[0].toUpperCase().localeCompare((l[0]+u[0]+c[0]).toUpperCase())&&(console.log("Reference allele is not correct for variant 0"),a=!0);else{let e,n,o=0;for(const i of t.variant){let a="",l="";if(!(0!=i.ref.length&&"-"!=i.ref\|\|"-"!=i.alt&&0!=i.alt.length))throw"Both Ref and Alt alleles are missing";if(0==i.ref.length\|\|"-"==i.ref)a=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase(),l=a+i.alt,i.pos-=1;else if("-"==i.alt\|\|0==i.alt.length){const e=(await r.get_fasta(t.genome,i.chr+":"+i.pos+"-"+i.pos)).split("\n").slice(1).join("").toUpperCase();a=e+i.ref,l=e,i.pos-=1}else l=i.alt,a=i.ref;const c=i.pos,h=a.toUpperCase(),p=l.toUpperCase();0==o?(e=c-s,n=c+a.length+1+s):(c-s<e&&(e=c-s),c+a.length+1+s>n&&(n=c+a.length+1+s)),u.push(h),f.push(p),d.push(c),o+=1}o=0;for(const i of t.variant){const s=(await r.get_fasta(t.genome,i.chr+":"+e+"-"+d[o])).split("\n").slice(1).join("").toUpperCase(),a=(await r.get_fasta(t.genome,i.chr+":"+(d[o]+u[o].length+1)+"-"+n)).split("\n").slice(1).join("").toUpperCase(),m=s+u[o]+a,g=s+f[o]+a;console.log(i.chr+"."+d[o]+"."+u[o]+"."+f[o]),o+=1,l.push(s),c.push(a),h.push(m),p.push(g)}}const m=[];for(let t=0;t<e.length;t++){const n=e[t].sam_info.split("\t");m.push({read_sequence:n[9],start_position:Number(n[3]),cigar:n[5],flag:Number(n[1])})}const g=[];for(let t=0;t<u.length;t++)g.push({ref_position:Number(d[t]),refallele:u[t],altallele:f[t],refseq:h[t],altseq:p[t],leftflankseq:l[t],rightflankseq:c[t]});Number.isFinite(Number(t.strictness))\|\|(t.strictness=1);const y={reads:m,alleles:g,strictness:Number(t.strictness)},v=new Date,b=await o("indel",JSON.stringify(y)),_=new Date;console.log("Time taken to run rust indel pipeline:",_-v,"ms");const w=b.split("\n");let x,k,q,N,S,A,M=0;for(let t of w)t.includes("Final_output:")?x=JSON.parse(JSON.parse(t.replace("Final_output:",""))):1==u.length&&t.includes("fisher_strand:")?(k=JSON.parse(t.replace("fisher_strand:","")),q=k.alternate_forward_count,N=k.alternate_reverse_count,S=k.reference_forward_count,A=k.reference_reverse_count,M=k.p_value):console.log(t);let T=!1;1==t.variant.length&&M>60&&(T=!0);const C=i.make_type2group(t);t.variant.length;let j=1;for(let n=0;n<x.length;n++){const r=x[n],o=r.read_number,s=r.categories,a=r.categories[0],l=[];if(s.length>1){for(let t=1;t<s.length;t++)l.push(s[t]);s.length-1>j&&(j=s.length-1)}if(a.includes("alt"))for(let n=0;n<t.variant.length;n++)a=="alt"+n.toString()&&C[i.type_supportalt+n.toString()]&&(e[o].tempscore=["alt"+n.toString()],C[i.type_supportalt+n.toString()].templates.push(e[o]));else"ref"==a?C[i.type_supportref]&&(e[o].tempscore=["ref"],C[i.type_supportref].templates.push(e[o])):"none"==a?C[i.type_supportno]&&(e[o].tempscore=l,C[i.type_supportno].templates.push(e[o])):"amb"==a?C[i.type_supportamb]&&(e[o].tempscore=l,C[i.type_supportamb].templates.push(e[o])):console.log("Unaccounted group, please check")}const O=[];for(const e in C){const r=C[e];if(0!=r.templates.length){if(e.includes(i.type_supportalt))for(let n=0;n<t.variant.length;n++)e==i.type_supportalt+n.toString()&&(1==t.variant.length?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the alternative allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the alternative allele"}):1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read support the alternative allele with "+f[n]+" sequence"}):r.messages.push({isheader:!0,t:r.templates.length+" reads support the alternative allele with "+f[n]+" sequence"}));else e==i.type_supportamb?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" ambiguous read"}):r.messages.push({isheader:!0,t:r.templates.length+" ambiguous reads"}):e==i.type_supportref?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting the reference allele"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting the reference allele"}):e==i.type_supportno?1==r.templates.length?r.messages.push({isheader:!0,t:r.templates.length+" read supporting neither reference nor alternative alleles"}):r.messages.push({isheader:!0,t:r.templates.length+" reads supporting neither reference nor alternative alleles"}):console.log("Unaccounted group, please check");r.widths=n,O.push(r)}}const E=[];for(let t=0;t<O.length;t++)O[t].type.includes("support_alt")&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_ref"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_no"==O[t].type&&E.push(O[t]);for(let t=0;t<O.length;t++)"support_amb"==O[t].type&&E.push(O[t]);return{groups:E,refalleleerror:a,ref_positions:d,refalleles:u,altalleles:f,max_diff_score:j,min_diff_score:0,strand_probability:M,strand_significance:T,refseqs:h,altseqs:p,leftflankseqs:l,rightflankseqs:c,alternate_forward_count:q,alternate_reverse_count:N,reference_forward_count:S,reference_reverse_count:A}}},1270:(t,e,n)=>{const r=n(9699),o=n(3856),i=n(6718).createCanvas,s=n(2273).basecolor;t.exports=async(t,e)=>{try{const[n,a,l]=r.fileurl(t);if(n)throw n;let c=t.query.usegrade;const 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o}t.exports=t=>async(e,n)=>{try{const r=e.query,s=t[r.genome];if(!s)throw"unknown genome";let c=null;if(r.file)r.file=o.join(a.tpmasterdir,r.file);else{if(!r.url)throw"file or url missing";c=await i.cache_index(r.url,r.indexURL)}const u=await i.tabix_is_nochr(r.file\|\|r.url,c,s),f=await l(r,c,u);n.send(f)}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message\|\|t})}}},8145:(t,e,n)=>{const r=n(9699),o=(n(1017),n(7147),n(3856)),i=n(6718).createCanvas,s=n(2273).nt2aa,a=n(2818).X,l=400,c="rgba(122,103,44,.7)",u="#edad0c",f="rgba(255,0,0,.5)",d="#ccc";function h(t,e,n,r,o){if(!t)return;if(!o.name&&!o.isoform)return;const i=[];o.name&&i.push(o.name),o.isoform&&i.push(o.isoform),t.push({chr:o.chr,start:o.start,stop:o.stop,x1:e,x2:n,y:r,isoform:o.isoform,name:i.join(" ")})}function p(t,e,n,r,o,i){const s=i/2,a=i/2,l=Math.max(i/2,6);if(o-2s<a)return;const c=Math.ceil((o-2s)/(a+l));if(c<=0)return;const u="+"==e;let f=Math.ceil(n+(o-ac-l(c-1))/2);for(let e=0;e<c;e++)t.beginPath(),u?(t.moveTo(f,r),t.lineTo(f+a,r+i/2),t.moveTo(f+a,r+i/2+1),t.lineTo(f,r+i)):(t.moveTo(f+a,r),t.lineTo(f,r+i/2),t.moveTo(f,r+i/2+1),t.lineTo(f+a,r+i)),t.stroke(),f+=a+l}t.exports=t=>async(e,n)=>{try{n.send(await async function(t,e){const[n,m,g]=r.fileurl(t);if(n)throw n;let y,v,b,_,w;if(t.query.fileIsBigbed=await o.testIfFileIsBigbed(m),t.query.getdata)t.query.getBED;else{if(y=Number(t.query.stackheight),v=Number(t.query.stackspace),b=Number(t.query.regionspace),_=Number(t.query.width),Number.isNaN(y))throw"stackheight is not integer";if(w=Math.max(10,y-2),Number.isNaN(v))throw"stackspace is not integer";if(Number.isNaN(b))throw"regionspace is not integer";if(Number.isNaN(_))throw"width is not a number"}if(t.query.usevalue){if(!t.query.usevalue.key)throw".key missing from .usevalue";if(t.query.usevalue.dropBelowCutoff&&(t.query.usevalue.dropBelowCutoff=Number(t.query.usevalue.dropBelowCutoff),Number.isNaN(t.query.usevalue.dropBelowCutoff)))throw".usevalue.dropBelowCutoff is not number"}if(t.query.bplengthUpperLimit&&(t.query.bplengthUpperLimit=Number(t.query.bplengthUpperLimit),Number.isNaN(t.query.bplengthUpperLimit)))throw"bplengthUpperLimit not number";if(!t.query.rglst)throw"no rglst[]";if(!Array.isArray(t.query.rglst))throw"rglst is not an array";if(0==t.query.rglst.length)throw"empty rglst";for(const e of t.query.rglst)e.reverse?e.scale=t=>Math.ceil(e.width(e.stop-t)/(e.stop-e.start)):e.scale=t=>Math.ceil(e.width(t-e.start)/(e.stop-e.start));const x=t.query.color\|\|"#3D7A4B",k=t.query.gmregion\|\|null,q=t.query.isoform,N=t.query.onerow,S=t.query.categories\|\|null,A=t.query.__isgene;let M;!t.query.fileIsBigbed&&g&&(M=await o.cache_index(m,t.query.indexURL));const T=await async function(t,e,n,r,i){let s;if(r){const l=[];if(t.fileIsBigbed){const n=await o.query_bigbed_by_coord(e,r.chr,r.start,r.stop);for(const e of n){const n=e.split("\t"),r=a(n);r.chr=n[0],r.start=Number(n[1]),r.stop=Number(n[2]),r.rglst=[];for(let e=0;e<t.rglst.length;e++){const n=t.rglst[e];Math.max(r.start,n.start)<Math.min(r.stop,n.stop)&&r.rglst.push({idx:e})}0!=r.rglst.length&&l.push(r)}}else await o.get_lines_bigfile({args:[e,r.chr+":"+r.start+"-"+r.stop],dir:n,callback:e=>{const n=e.split("\t");let r={};if(t.getBED)r.rest=n.slice(3);else if(n[3])try{r=JSON.parse(n[3])}catch(t){return void(s=e)}if(!r.isoformonly\|\|r.isoformonly==i){r.chr=n[0],r.start=Number(n[1]),r.stop=Number(n[2]),r.rglst=[];for(let e=0;e<t.rglst.length;e++){const n=t.rglst[e];Math.max(r.start,n.start)<Math.min(r.stop,n.stop)&&r.rglst.push({idx:e})}0!=r.rglst.length&&l.push(r)}}});if(s)throw"Line with invalid JSON: "+s;return[l]}const l=[];for(const[r,i]of t.rglst.entries()){const c=[];if(t.fileIsBigbed){const t=await o.query_bigbed_by_coord(e,i.chr,i.start,i.stop);for(const e of t){const t=e.split("\t"),n=a(t);n.chr=t[0],n.start=Number(t[1]),n.stop=Number(t[2]),n.rglst=[{idx:r}],c.push(n)}}else await o.get_lines_bigfile({args:[e,i.chr+":"+i.start+"-"+i.stop],dir:n,callback:e=>{const n=e.split("\t");let o={};if(t.getBED)o.rest=n.slice(3);else if(n[3])try{o=JSON.parse(n[3])}catch(t){return void(s=e)}o.chr=n[0],o.start=Number(n[1]),o.stop=Number(n[2]),o.rglst=[{idx:r}],c.push(o)}});l.push(c)}if(s)throw"Line with invalid JSON: "+s;return l}(t.query,m,M,k,q);let C;t.query.filterByName&&(C=new Set(t.query.filterByName.split(/[\s\n]/).map((t=>t.trim()))));const j=[];for(const e of T)for(const n of e){if(t.query.usevalue){const e=n[t.query.usevalue.key];if(!Number.isFinite(e))continue;if(t.query.usevalue.dropBelowCutoff&&e<t.query.usevalue.dropBelowCutoff)continue}if(!(t.query.bplengthUpperLimit&&n.stop-n.start>t.query.bplengthUpperLimit)){if(C)if(n.isoform){if(!C.has(n.isoform))continue}else{if(!n.name)continue;if(!C.has(n.name))continue}j.push(n)}}if(t.query.getdata)return{items:j};if(0==j.length){const e=i(_t.query.devicePixelRatio,yt.query.devicePixelRatio),n=e.getContext("2d");return t.query.devicePixelRatio>1&&n.scale(t.query.devicePixelRatio,t.query.devicePixelRatio),n.font=y+"px Arial",n.fillStyle="#aaa",n.textAlign="center",n.textBaseline="middle",n.fillText("No data in view range",_/2,y/2),{src:e.toDataURL(),height:y}}const O=Math.ceil(y/4)-1;if(N\|\|j.length>=600){const e=j.length<200,n=i(_t.query.devicePixelRatio,yt.query.devicePixelRatio),r=n.getContext("2d");t.query.devicePixelRatio>1&&r.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);const o=j.length<=200?[]:null;for(const n of j){const i=S&&n.category&&S[n.category]?S[n.category].color:n.color\|\|x;r.fillStyle=i;for(const i of n.rglst){let s=0;for(let e=0;e<i.idx;e++)s+=t.query.rglst[e].width+b;const a=t.query.rglst[i.idx],l=[];n.utr5&&l.push(...n.utr5),n.utr3&&l.push(...n.utr3),!n.exon\|\|n.coding&&0!=n.coding.length\|\|l.push(...n.exon);for(const t of l){const e=Math.max(a.start,t[0]),i=Math.min(a.stop,t[1]),l=s+a.scale(a.reverse?i:e),c=s+a.scale(a.reverse?e:i);r.fillRect(l,O,Math.max(1,c-l),y-2O),h(o,l,c,1,n)}const c=[];n.exon?n.coding&&n.coding.length>0&&c.push(...n.coding):c.push([n.start,n.stop]);for(const t of c){const i=Math.max(a.start,t[0]),l=Math.min(a.stop,t[1]),c=s+a.scale(a.reverse?l:i),u=s+a.scale(a.reverse?i:l);r.fillRect(c,0,Math.max(1,u-c),y),h(o,c,u,1,n),n.strand&&e&&(r.strokeStyle="white",p(r,n.strand,c,O,u-c,y-2O))}}}return{src:n.toDataURL(),height:y,mapisoform:o}}if(t.query.hideItemNames)for(const t of j)delete t.name;let E=null;if(A&&j.length<50){E=[];for(const t of j){const e={};for(const n in t)"canvas"!=n&&"rglst"!=n&&(e[n]=t[n]);E.push(e)}}const R=t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0),I=t.query.translatecoding&&R<3_;let P;if(I){if(!t.query.genome)throw"genome missing for translating genes";if(P=e[t.query.genome],!P)throw"invalid genome"}const F=[],L=i(10,10);let D=L.getContext("2d");t.query.devicePixelRatio>1&&D.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);D.font="bold "+w+"px Arial";const z=j.length<l,B=j.length<l?[]:null;let $=!1;k&&($=k.reverse);for(const e of t.query.rglst)e.reverse&&($=!0);j.sort(((t,e)=>$?t.stop==e.stop?t.start-e.start:e.stop-t.stop:t.start==e.start?e.stop-t.stop:t.start-e.start));const Z=j.some((t=>t.exon)),G=[0];let U=1,W=null;for(const e of j){let n=null,r=null;for(const o of e.rglst){let i=0;for(let e=0;e<o.idx;e++)i+=t.query.rglst[e].width+b;const s=t.query.rglst[o.idx],a=Math.max(e.start,s.start),l=Math.min(e.stop,s.stop);if(a<l){const t=i+s.scale(s.reverse?l:a),e=i+s.scale(s.reverse?a:l);null==n?(n=t,r=e):(n=Math.min(n,t),r=Math.max(r,e))}}if(null==n)continue;e.canvas={start:n,stop:r,stranded:null!=e.strand},e.coding&&I&&(e.willtranslate=!0,F.push(e));let o=n,i=r;if(z){const t=e.name;if(t){e.canvas.namestr=t;const n=D.measureText(t).width;e.canvas.namewidth=n,Z?e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):n>e.canvas.stop-e.canvas.start?e.canvas.start>_-e.canvas.stop?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):(e.canvas.namehover=!0,e.canvas.textalign="left"):Math.min(_,e.canvas.stop)-Math.max(0,e.canvas.start)>=n+20?e.canvas.namein=!0:e.canvas.start>=n+1?(e.canvas.namestart=e.canvas.start-1,o=e.canvas.namestart-n,e.canvas.textalign="right"):e.canvas.stop+n+1<=_?(e.canvas.namestart=e.canvas.stop+1,i=e.canvas.namestart+n,e.canvas.textalign="left"):e.canvas.namein=!0}}e.canvas.stop-e.canvas.start>.3_&&(W=[]);for(let t=1;t<=U;t++)if(null==G[t]\|\|G[t]<o){e.canvas.stack=t,G[t]=i;break}null==e.canvas.stack&&(U++,G[U]=i,e.canvas.stack=U),h(B,o,i,e.canvas.stack,e)}L.width=_t.query.devicePixelRatio;const J=(y+v)U-v;L.height=Jt.query.devicePixelRatio,D=L.getContext("2d"),t.query.devicePixelRatio>1&&D.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);D.font="bold "+w+"px Arial",D.textBaseline="middle",D.lineWidth=1;for(const e of j){const n=e.canvas;if(!n)continue;const r=S&&e.category&&S[e.category]?S[e.category].color:e.color\|\|x,o=(y+v)(n.stack-1);D.fillStyle=r,(e.exon\|\|e.rglst.length>1)&&(D.strokeStyle=r,D.beginPath(),D.moveTo(n.start,Math.floor(o+y/2)+.5),D.lineTo(n.stop,Math.floor(o+y/2)+.5),D.stroke());for(const i of e.rglst){let s=0;for(let e=0;e<i.idx;e++)s+=t.query.rglst[e].width+b;const a=t.query.rglst[i.idx],l=[];e.utr3&&l.push(...e.utr3),e.utr5&&l.push(...e.utr5),!e.exon\|\|e.coding&&0!=e.coding.length\|\|l.push(...e.exon);for(const t of l){const n=Math.max(t[0],a.start),i=Math.min(t[1],a.stop);if(n<i){if(e.exon2color)for(const t of e.exon2color)if(n>=t.start&&i<=t.stop){D.fillStyle=t.color;break}const t=s+a.scale(a.reverse?i:n),l=s+a.scale(a.reverse?n:i);D.fillRect(t,o+O,Math.max(1,l-t),y-2O),e.exon2color&&(D.fillStyle=r)}}const c=[];e.exon?e.coding&&e.coding.length>0&&c.push(...e.coding):c.push([e.start,e.stop]);let u=e.strand;n.stranded&&a.reverse&&(u="+"==e.strand?"-":"+");for(const t of c){const i=Math.max(t[0],a.start),l=Math.min(t[1],a.stop);if(i<l){if(e.exon2color)for(const t of e.exon2color)if(i>=t.start&&l<=t.stop){D.fillStyle=t.color;break}const t=s+a.scale(a.reverse?l:i),c=s+a.scale(a.reverse?i:l);if(D.fillRect(t,o,Math.max(1,c-t),y),e.exon2color&&(D.fillStyle=r),n.stranded&&!e.willtranslate)if(D.strokeStyle="white",n.namein){const e=(c-t-n.namewidth)/2;p(D,u,t,o+O,e,y-2O),p(D,u,t+e+n.namewidth,o+O,e,y-2O)}else p(D,u,t,o+O,c-t,y-2O)}}if(n.stranded&&e.intron){D.strokeStyle=r;for(const t of e.intron){const e=Math.max(t[0],a.start),n=Math.min(t[1],a.stop);if(e<n){const t=s+a.scale(a.reverse?n:e);p(D,u,t,o+O,s+a.scale(a.reverse?e:n)-t,y-2O)}}}if(W&&e.exon){for(let t=0;t<e.exon.length;t++){const r=e.exon[t];if(r[1]<=a.start\|\|r[0]>=a.stop)continue;const o=Math.max(r[0],a.start),i=Math.min(r[1],a.stop);if(o<i){const l=s+a.scale(a.reverse?i:o),c=s+a.scale(a.reverse?o:i);W.push({chr:e.chr,start:Math.min(r[0],r[1]),stop:Math.max(r[0],r[1]),x1:l,x2:c,y:n.stack,name:"Exon "+(t+1)+"/"+e.exon.length})}}for(let t=1;t<e.exon.length;t++){const r=e.exon["+"==e.strand?t-1:t][1],o=e.exon["+"==e.strand?t:t-1][0];if(o<=a.start\|\|r>=a.stop)continue;const i=Math.max(r,a.start),l=Math.min(o,a.stop);if(i<l){const c=s+a.scale(a.reverse?l:i),u=s+a.scale(a.reverse?i:l);if(u<0)continue;W.push({chr:e.chr,start:r,stop:o,x1:c,x2:u,y:n.stack,name:"Intron "+t+"/"+(e.exon.length-1)})}}}}if(null!=n.namestart)D.textAlign=n.textalign,D.fillStyle=r,D.fillText(n.namestr,n.namestart,o+y/2);else if(n.namehover&&!t.query.noNameHover){const t=Math.max(10,n.start+10);D.fillStyle="white",D.fillRect(t,o,n.namewidth+10,y),D.strokeStyle=r,D.strokeRect(t+1.5,o+.5,n.namewidth+10-3,y-2),D.fillStyle=r,D.textAlign="center",D.fillText(n.namestr,t+n.namewidth/2+5,o+y/2)}else n.namein&&(D.textAlign="center",D.fillStyle="white",D.fillText(n.namestr,(Math.max(0,n.start)+Math.min(_,n.stop))/2,o+y/2))}const H={height:J,mapisoform:B,mapexon:W,returngmdata:E};if(0==F.length)return H.src=L.toDataURL(),H;const V=[];D.textAlign="center",D.textBaseline="middle";for(const[e,n]of F.entries()){const e=S&&n.category&&S[n.category]?S[n.category].color:n.color\|\|x,r=n.canvas,i=(y+v)(r.stack-1);n.genomicseq=(await o.get_fasta(P,n.chr+":"+(n.start+1)+"-"+n.stop)).split("\n").slice(1).join("").toUpperCase();const a=s(n);for(const e of n.rglst){const o=t.query.rglst[e.idx];let s=0;for(let n=0;n<e.idx;n++)s+=t.query.rglst[n].width+b;const l=o.width/(o.stop-o.start),h=Math.min(y,3l),p=h<8?null:h;let m=!1;r.stranded&&"-"==n.strand&&(m=!0);let g=0;p&&(D.font=p+"px Arial");for(const[t,e]of n.coding.entries()){let[r,h]=e;if(m){if(r>=o.stop){g+=h-r,0==t&&n.startCodonFrame&&(g-=3-n.startCodonFrame);continue}if(h<=o.start)break}else{if(h<=o.start){g+=h-r,0==t&&n.startCodonFrame&&(g-=3-n.startCodonFrame);continue}if(r>=o.stop)break}if(0==t&&n.startCodonFrame){m?h-=3-n.startCodonFrame:r+=3-n.startCodonFrame;let t=Math.max(e[0],o.start),a=Math.min(e[1],o.stop);if(m?t=Math.max(h,o.start):a=Math.min(r,o.stop),t<a){D.fillStyle=d;const e=s+o.scale(o.reverse?a:t),n=s+o.scale(o.reverse?t:a);D.fillRect(e,i,Math.max(1,n-e),y)}}const v=Math.max(o.start,r),b=Math.min(o.stop,h);g+=m?h-b:v-r;let _=0;for(let t=0;t<b-v;t++){let e;if(g++,_++,g%3==0)e=g/3-1;else{if(t<b-v-1)continue;e=Math.floor(g/3)}let r=a[e],d=Math.ceil(g/3)%2==0?c:null;r?"M"==r?d=u:""==r&&(d=f):(r=4,d="red");let h,w=l_;if(m){const e=b-1-t;h=s+o.scale(e)}else{const 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function(t,e,n){if(!t)return;if(!t.chr2bcffile)throw"vcftk.chr2bcffile is missing";{if("object"!=typeof t.chr2bcffile)throw"chr2bcffile not an object";for(const e in t.chr2bcffile)t.chr2bcffile[e]=r.join(a.tpmasterdir,t.chr2bcffile[e]);const n={file:t.chr2bcffile[e.defaultcoord.chr]};if(!n.file)throw"default chr missing from chr2bcffile";await o.init_one_vcf(n,e,!0),t.info=n.info,t.format=n.format,t.samples=n.samples,t.nochr=n.nochr}if(t.AD&&t.AD.chr2bcffile){if("object"!=typeof t.AD.chr2bcffile)throw"AD.chr2bcffile not an object";for(const e in t.AD.chr2bcffile)t.AD.chr2bcffile[e]=r.join(a.tpmasterdir,t.AD.chr2bcffile[e]);const i={file:t.AD.chr2bcffile[e.defaultcoord.chr]};if(!i.file)throw"default chr missing from AD.chr2bcffile";await o.init_one_vcf(i,e,!0),t.AD.info=i.info,t.AD.format=i.format,t.AD.samples=i.samples,t.AD.nochr=i.nochr,console.log(n.label+" vcf: AD: "+t.AD.samples.length+" samples");for(const e of t.AD.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}}if(t.samples){for(const e of t.samples){const t=Number(e.name);if(!Number.isInteger(t))throw"non-integer vcf sample: "+e.name;e.name=t}console.log(n.label+" vcf: "+t.samples.length+" samples")}else console.log(n.label+" vcf: no samples");if(t.numerical_axis&&t.numerical_axis.info_keys){if(!Array.isArray(t.numerical_axis.info_keys))throw"numerical_axis.info_keys should be an array";for(const e of t.numerical_axis.info_keys){const n=t.info[e.key];if(!n)throw'INFO field "'+e.key+'" not found for numerical_axis';if("Float"!=n.Type&&"Integer"!=n.Type)throw'INFO field "'+e.key+'" from numerical_axis not of integer or float type';if("1"!=n.Number&&"A"!=n.Number)throw'for numerical axis, INFO field "'+e.key+'" only allows to be Number=1 or Number=A'}}if(t.plot_mafcov){if(!t.AD)throw".plot_mafcov enabled but .AD{} missing from vcf";if(!t.AD.samples)throw".plot_mafcov enabled but no samples from 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vcf";if(!t.format)throw".termdb_bygenotype enabled but no FORMAT fields from vcf";if(!t.format.GT)throw".termdb_bygenotype enabled but the GT FORMAT field is missing";if(!n.cohort)throw"termdb_bygenotype but ds.cohort missing";if(!n.cohort.termdb)throw"termdb_bygenotype but ds.cohort.termdb missing";if(t.termdb_bygenotype.getAF){if(!t.termdb_bygenotype.termid_sex)throw"termid_sex missing for getAF at termdb_bygenotype";if(!t.termdb_bygenotype.value_male)throw"value_male missing for getAF at termdb_bygenotype";const e=n.cohort.termdb.q.getSample2value(t.termdb_bygenotype.termid_sex);t.termdb_bygenotype.male_samples=new Set;for(const n of e)n.value==t.termdb_bygenotype.value_male&&t.termdb_bygenotype.male_samples.add(n.sample);if(!t.termdb_bygenotype.sex_chrs)throw"sex_chrs missing for getAF at termdb_bygenotype";if(!Array.isArray(t.termdb_bygenotype.sex_chrs))throw"sex_chrs is not array";t.termdb_bygenotype.sex_chrs=new Set(t.termdb_bygenotype.sex_chrs)}}if(t.samples){t.sample2arrayidx=new Map;for(const[e,n]of t.samples.entries())t.sample2arrayidx.set(n.name,e)}}(n.vcf,e,t),function(t){if(!t.info_fields)return;if(!Array.isArray(t.info_fields))throw"tk.info_fields is not array";for(const e of t.info_fields){if(!e.key)throw".key missing from one of tk.info_fields[]";if(t.vcf&&t.vcf.info&&!t.vcf.info[e.key])throw`info field ${e.key} missing from tk.vcf.info{}`;if(e.label\|\|(e.label=e.key),e.iscategorical){if(!Array.isArray(e.values))throw".values[] not an array of categorical INFO field: "+e.key;for(const t of e.values){if(!t.key)throw"key missing from a value of categorical INFO: "+e.key;t.label\|\|(t.label=t.key)}}else if(e.isfloat\|\|e.isinteger){if(!e.range)throw".range{} missing from a numerical INFO: "+e.key;s(e.range,"tk.info_fields[]")}else if(!e.isflag)throw"tk.info_fields unknown type: "+e.key}}(n),await async function(t,e,n){if(!t)return;if(!Array.isArray(t.tracks))throw"ld.tracks[] not an 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e.vcf&&(n.vcf={numerical_axis:e.vcf.numerical_axis,format:e.vcf.format,info:e.vcf.info,check_pecanpie:e.vcf.check_pecanpie},e.vcf.plot_mafcov&&(n.vcf.plot_mafcov={},t.cohort&&t.cohort.termdb&&(n.vcf.plot_mafcov.overlay_term=e.vcf.plot_mafcov.overlay_term\|\|{})),e.vcf.termdb_bygenotype&&(n.vcf.termdb_bygenotype=!0),e.populations&&(n.populations=e.populations)),e.ld&&(n.ld={tracks:e.ld.tracks.map((t=>({name:t.name,shown:t.shown}))),overlay:e.ld.overlay}),n}async function h(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(c+t,new Map);let i=0;for(const s of(await o.read_file(r.join(a.tpmasterdir,t))).trim().split("\n")){i++;const t=s.split("\t"),r=Number(t[0]);if(!Number.isInteger(r))throw"non-integer sample id from a line of restrictAncestries pc file";for(let o=1;o<=e;o++){const e=c+o,i=Number(t[o]);if(Number.isNaN(i))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(r,i)}}return console.log(i,"samples loaded from "+t),Object.freeze(n)}},7510:(t,e,n)=>{n(9699),n(7147),n(1017);const r=n(3856),o=(n(2273),n(6280)),i=n(6234),s=n(2581);e.handle_request=t=>async(e,n)=>{const a=e.query;try{const e=t[a.genome],l=await async function(t,e){if(!e)throw"invalid genome";if(t.dslabel){const n=e.datasets[t.dslabel];if(!n)throw"invalid dslabel";if(!n.track)throw"no mds2 track found for dataset";return n}const n={iscustom:1,track:{}};t.vcf&&(n.track.vcf=t.vcf,await r.init_one_vcf(n.track.vcf,e));t.ld;return n}(a,e);if(a.trigger_overlayld)return await s.overlay(a,l,n);a.hidden_mclass&&(a.hidden_mclass=new Set(a.hidden_mclass));const c={mclass2count:{}};if(a.info_fields){c.info_fields={};for(const t of a.info_fields)if(t.iscategorical)c.info_fields[t.key]={value2count:{}};else if(t.isnumerical)c.info_fields[t.key]={filteredcount:0};else{if(!t.isflag)throw"unknown info type";c.info_fields[t.key]={count_yes:0,count_no:0}}}if(a.trigger_mafcovplot&&await i.plot(a,e,l,c),a.trigger_vcfbyrange&&(await 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e=["cnv.cnv_change","cnv.gene_level_cn","cnv.consequence.gene.symbol","case.submitter_id","case.case_id"];function n(t){const n=e.slice();if(t.twLst)for(const e of t.twLst){let t=e.term.id;t.startsWith("case.")&&(t="occurrence."+t),n.push(t)}return n.join(",")}function o(t){if(!t.gene&&"string"!=typeof t.gene)throw"p.gene does not provide non-empty string";const e={op:"and",content:[]};return t.gene&&e.content.push({op:"=",content:{field:"cnv.consequence.gene.symbol",value:t.gene.split(",")}}),t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push((0,u.P)("string"==typeof t.filterObj?JSON.parse(t.filterObj):t.filterObj)),e}t.queries.geneCnv.bygene.get=async t=>{var e;const i=S(t),a=await s().post(l().join(f,"cnv_occurrences"),{headers:i,body:JSON.stringify({size:1e5,fields:n(t),filters:o(t)})}),c=JSON.parse(a.body);if(!Array.isArray(null==c\|\|null===(e=c.data)\|\|void 0===e?void 0:e.hits))throw"geneCnv response body is not {data:hits[]}";const 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n.term\|\|(n.term={id:n.id})}async function C(t,e,n,r){if(T(e),r){if(!Array.isArray(r))throw"geneTwLst not array";t.isoforms=[];for(const e of r){var i;if(null==e\|\|null===(i=e.term)\|\|void 0===i\|\|!i.name)throw"gene tw missing .term.name";if(e.term.isoform)t.isoforms.push(e.term.isoform);else{var a,u;if("object"!=typeof t.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(null===(a=t.genome)\|\|void 0===a\|\|null===(u=a.genedb)\|\|void 0===u\|\|!u.get_gene2canonicalisoform)throw"gene2canonicalisoform not supported on this genome";const n=t.genome.genedb.get_gene2canonicalisoform.get(e.term.name);if(null==n\|\|!n.isoform)continue;t.isoforms.push(n.isoform)}}}"samples"==t.get&&((t.ssm_id_lst\|\|t.isoform)&&(e.some((t=>"ssm.ssm_id"==t.id))\|\|e.push({term:{id:"ssm.ssm_id"}}),e.some((t=>"case.observation.read_depth.t_alt_count"==t.id))\|\|e.push({term:{id:"case.observation.read_depth.t_alt_count"}}),e.some((t=>"case.observation.read_depth.t_depth"==t.id))\|\|e.push({term:{id:"case.observation.read_depth.t_depth"}}),e.some((t=>"case.observation.read_depth.n_depth"==t.id))\|\|e.push({term:{id:"case.observation.read_depth.n_depth"}}),e.some((t=>"case.observation.sample.tumor_sample_uuid"==t.id))\|\|e.push({term:{id:"case.observation.sample.tumor_sample_uuid"}})),e.some((t=>"case.case_id"==t.id))\|\|e.push({term:{id:"case.case_id"}}),e.some((t=>"case.submitter_id"==t.id))\|\|e.push({term:{id:"case.submitter_id"}})),"summary"!=t.get&&"sunburst"!=t.get\|\|e.some((t=>"case.submitter_id"==t.id))\|\|e.push({term:{id:"case.submitter_id"}});const d=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&d.push({term:e,q:t.q})}const h=e.map((t=>t.term.id));t.hiddenmclass&&(h.push("ssm.consequence.transcript.consequence_type"),h.push("ssm.consequence.transcript.transcript_id")),t.rglst&&(h.push("ssm.chromosome"),h.push("ssm.start_position"));const p={size:1e4,fields:h.join(",")};_(t,n),p.filters=Z.filters(t,n);const m=S(t),g=await s().post(l().join(f,Z.endpoint),{headers:m,body:JSON.stringify(p)});let y;delete t.isoforms;try{y=JSON.parse(g.body)}catch(t){throw"invalid JSON from GDC for variant2samples query"}if(!y.data\|\|!y.data.hits)throw"variant2samples data structure not data.hits[]";if(!Array.isArray(y.data.hits))throw"variant2samples re.data.hits is not array for query";const v=[];for(const e of y.data.hits){if(!e.case)throw"variant2samples .case{} missing from a hit";const r={};if(e.ssm&&(r.ssm_id=e.ssm.ssm_id),t.hiddenmclass){var b;if(!Array.isArray(null===(b=e.ssm)\|\|void 0===b?void 0:b.consequence))continue;const n={};if(x(n,e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform))),t.hiddenmclass.has(n.class))continue}if(t.rglst){var w,k;if(null===(w=e.ssm)\|\|void 0===w\|\|!w.chromosome\|\|null===(k=e.ssm)\|\|void 0===k\|\|!k.start_position)continue;if(!t.rglst.find((t=>t.chr==e.ssm.chromosome&&t.start<e.ssm.start_position&&t.stop>=e.ssm.start_position)))continue}var q,N,C,R;if(t.variant2samples?r.sample_id=await j(e.case,n,!1):(r.sample_id=e.case.case_id,r.__sampleName=e.case.submitter_id),e.case.case_id)r.sample_URLid=e.case.case_id,null!==(q=e.case)&&void 0!==q&&null!==(N=q.observation)&&void 0!==N&&null!==(C=N[0])&&void 0!==C&&null!==(R=C.sample)&&void 0!==R&&R.tumor_sample_uuid&&(r.sample_URLid=r.sample_URLid+"?bioId="+e.case.observation[0].sample.tumor_sample_uuid);for(const t of d)A(r,e.case,t);O(e.case,r),E(r,n),v.push(r)}if(function(t,e){for(const r of e){var n;if(("integer"==r.term.type\|\|"float"==r.term.type)&&null!==(n=r.q)&&void 0!==n&&n.mode)if("discrete"==r.q.mode\|\|"binary"==r.q.mode){const e={};for(const n of t){const t=n[r.term.id];Number.isFinite(t)&&("min"in e?(e.min=Math.min(t,e.min),e.max=Math.max(t,e.max)):(e.min=t,e.max=t))}const n=(0,o.compute_bins)(r.q,(t=>e));for(const e of t){const t=e[r.term.id];Number.isFinite(t)&&(e[r.term.id]=M(n,t))}}else if("continuous"!=r.q.mode)throw"mayApplyBinning: unknown numeric q.mode"}}(v,d),r){const t={gene:r.map((t=>t.term.name)).join(","),twLst:d},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)v.push(e)}const I=new Map;for(const t of v)(0,c.z9)([t],I,t.ssm_id);return[...I.values()]}async function j(t,e,n){var r,o,i;return n&&t.case_id?t.case_id:null!=t&&null!==(r=t.observation)&&void 0!==r&&null!==(o=r[0])&&void 0!==o&&null!==(i=o.sample)&&void 0!==i&&i.tumor_sample_uuid?await e.aliquot2submitter.get(t.observation[0].sample.tumor_sample_uuid):t.case_id\|\|t.submitter_id}function O(t,e){if(!t.observation)return;const n=t.observation[0];n&&n.read_depth&&(e.formatK2v={TumorAC:n.read_depth.t_depth-n.read_depth.t_alt_count+","+n.read_depth.t_alt_count,NormalDepth:n.read_depth.n_depth})}function E(t,e){var n;const r=t["case.project.project_id"];r&&(t.caseIsOpenAccess=null===(n=e.gdcOpenProjects)\|\|void 0===n?void 0:n.has(r))}async function R(t,e,n,r){T(t);const o=[];for(const e of t)e.term&&"categorical"==e.term.type&&o.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const i=function(t){const e=[];for(const n of t)if(n.id)if(n.type="categorical")e.push(n.path+" {buckets { doc_count, key }}");else{if("integer"!=n.type&&"float"!=n.type)throw"unknown term type";e.push(n.path+" {stats { count }}")}const n=`query termislst2total( $filters: FiltersArgument) {\n\t\texplore {\n\t\t\tcases {\n\t\t\t\taggregations (filters: $filters, aggregations_filter_themselves: true) {\n\t\t\t\t\t${e.join("\n")}\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t}`;return n}(o),a=function(t,e){const n={filters:{op:"and",content:[{op:"in",content:{field:"cases.available_variation_data",value:["ssm"]}}]}};if(t&&t.tid2value)for(const r in t.tid2value){e.cohort.termdb.q.termjsonByOneid(r)&&n.filters.content.push({op:"in",content:{field:r.replace(/^case\./,"cases."),value:[t.tid2value[r]]}})}t&&t.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:t.ssm_id_lst.split(",")}});t.filterObj&&n.filters.content.push((0,u.P)(t.filterObj));return n}(e,r),l=await s().post(d,{headers:S(e),body:JSON.stringify({query:i,variables:a})});let c;try{c=JSON.parse(l.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+i+" and filter: "+filter}const f=["data","explore","cases","aggregations"];let h=c[f[0]];for(let t=1;t<f.length;t++)if(h=h[f[t]],!h)throw`.${f[t]} missing from data structure of termid2totalsize2 for query :${i} and filter: ${filter}`;for(const t of o){if("categorical"==t.type&&!Array.isArray(h[t.path].buckets))throw f.join(".")+" not array for query :"+i+" and filter: "+filter;if(("integer"==t.type\|\|"float"==t.type)&&"object"!=typeof h[t.path].stats)throw f.join(".")+" not object for query :"+i+" and filter: "+filter}const p=new Map;for(const t of o)if("categorical"==t.type){const e=h[t.path].buckets,n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);p.set(t.id,n)}else if("integer"==t.type\|\|"float"==t.type){const e=h[t.path].stats.count;p.set(t.id,{total:e})}return n?[p,n]:p}function I(t){const e=["consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change"];t.queries.snvindel.m2csq.get=async t=>{const n=await s()(f+"/ssms/"+t.ssm_id+"?fields="+e.join(","),{method:"GET",headers:S(t)});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid json in response"}if(!r.data\|\|!r.data.consequence)throw"returned data not .data.consequence";if(!Array.isArray(r.data.consequence))throw".data.consequence not array";return r.data.consequence.map((t=>t.transcript))}}function P(t,e){t.queries.singleSampleMutation.get=async(n,r)=>{if(!n)throw"sampleName missing";return r.case_id=t.map2caseid.get(n),r.case_id\|\|(r.case_id=await async function(t){const e=await s().post("https://api.gdc.cancer.gov/cases",{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:1,fields:"case_id,submitter_id",filters:{op:"or",content:[{op:"=",content:{field:"samples.portions.analytes.aliquots.aliquot_id",value:[t]}},{op:"=",content:{field:"submitter_id",value:[t]}},{op:"=",content:{field:"samples.submitter_id",value:[t]}}]}})}),n=JSON.parse(e.body);for(const t of n.data.hits)if(t.case_id)return t.case_id;throw"cannot convert to case_id (uuid)"}(n)),await L(r,t,e)}}function F(t){return async(e,n)=>{try{const r=t[e.query.genome];if(!r)throw"invalid genome";const o=r.datasets[e.query.dslabel];if(!o)throw"invalid dslabel";if(!e.query.case_id)throw".case_id missing";n.send({mlst:await L(e.query,o,r)})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message\|\|t})}}}async function L(t,e,n){const o=[];{const e=await s().post(l().join(f,$.endpoint),{headers:S(t),body:JSON.stringify({size:1e3,fields:$.fields.join(","),filters:$.filters(t)})}),n=JSON.parse(e.body);for(const t of n.data.hits){let e=t.consequence.find((t=>1==t.transcript.is_canonical));e\|\|(e=t.consequence[0]);const n=e.transcript.aa_change\|\|e.transcript.consequence_type,[i,s,a]=r.vepinfo(e.transcript.consequence_type);o.push({dt:r.dtsnvindel,mname:n,class:s,gene:e.transcript.gene.symbol,chr:t.chromosome,pos:t.start_position,ref:t.reference_allele,alt:t.tumor_allele})}}{const e=await async function(t){const e=S(t),n=await s().post(l().join(f,"files"),{headers:e,body:JSON.stringify({size:1e4,fields:["cases.samples.sample_type","data_type","file_id","data_format","experimental_strategy","analysis.workflow_type"].join(","),filters:function(t){if(!t.case_id)throw".case_id missing";return{op:"and",content:[{op:"in",content:{field:"cases.case_id",value:[t.case_id]}},{op:"in",content:{field:"data_type",value:["Masked Copy Number Segment","Copy Number Segment","Transcript Fusion"]}}]}}(t)})}),o=JSON.parse(n.body);if(!Array.isArray(o.data.hits))throw"re.data.hits[] not array";let i,a,c;for(const t of o.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){var u,d,h;const e=null===(u=t.cases)\|\|void 0===u\|\|null===(d=u[0].samples)\|\|void 0===d\|\|null===(h=d[0])\|\|void 0===h?void 0:h.sample_type;if(!e)continue;if(e.includes("Normal"))continue;if("Masked Copy Number Segment"!=t.data_type)continue;i=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;a=t.file_id;continue}}}else{var p;if("RNA-Seq"!=t.experimental_strategy)continue;if("Arriba"!=(null===(p=t.analysis)\|\|void 0===p?void 0:p.workflow_type))continue;if("Transcript Fusion"!=t.data_type)continue;c=t.file_id}const m=[];if(a){const t=(await s()(l().join(f,"data")+"/"+a,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(7!=n.length)continue;const o=Number(n[4]),i=Number(n[5]),s=Number(n[6]);if(Number.isNaN(o)\|\|Number.isNaN(i)\|\|Number.isNaN(s))continue;const a={dt:r.dtcnv,chr:n[1],start:Number(n[2]),stop:Number(n[3]),value:o};!a.chr\|\|Number.isNaN(a.start)\|\|Number.isNaN(a.stop)\|\|(m.push(a),o>0&&0==s&&i>0&&m.push({dt:r.dtloh,chr:a.chr,start:a.start,stop:a.stop,segmean:.5}))}}else if(i){const t=(await s()(l().join(f,"data")+"/"+i,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t");if(6!=n.length)continue;if(!n[1])continue;const o={dt:r.dtcnv,chr:"chr"+n[1],start:Number(n[2]),stop:Number(n[3]),value:Number(n[5])};Number.isNaN(o.start)\|\|Number.isNaN(o.stop)\|\|Number.isNaN(o.value)\|\|m.push(o)}}if(c)try{const t=(await s()(l().join(f,"data")+"/"+c,{method:"GET",headers:e})).body.split("\n");for(let e=1;e<t.length;e++){const n=t[e].split("\t"),o={dt:r.dtfusionrna,chrA:n[0],posA:Number(n[1]),chrB:n[3],posB:Number(n[4])};o.chrA&&o.chrB&&!Number.isNaN(o.posA)&&!Number.isNaN(o.posB)&&(N(o,n[6]),m.push(o))}}catch(t){}return m}(t);o.push(...e)}return o}function D(t){return async(e,n)=>{try{if(!t[e.query.genome])throw"invalid genome";n.send({genes:await z({filter:e.query.filter0,CGConly:parseInt(e.query.CGConly),maxGenes:e.query.maxGenes})})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message\|\|t})}}}async function z({filter:t,CGConly:e,maxGenes:n}){let r={op:"and",content:[]};if(t){if("object"!=typeof t)throw"filter not object";r=t}const o=await s().post(l().join(f,"/analysis/top_mutated_genes_by_project"),{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:n\|\|50,fields:"symbol",filters:B(r,e)})}),i=JSON.parse(o.body),a=[];for(const t of i.data.hits)t.symbol&&a.push(t.symbol);return a}function B(t,e){let n;if("in"==t.op)n={op:"and",content:[t]};else{if("and"!=t.op)throw'f.op not "in" or "and"';n=t}return n.content.push({op:"NOT",content:{field:"ssms.consequence.transcript.annotation.vep_impact",value:"missing"}}),n.content.push({op:"in",content:{field:"ssms.consequence.transcript.consequence_type",value:["missense_variant","frameshift_variant","start_lost","stop_lost","stop_gained"]}}),e&&n.content.push({op:"in",content:{field:"genes.is_cancer_gene_census",value:["true"]}}),n}const $={endpoint:"/ssms",size:1e5,fields:["ssm_id","chromosome","start_position","reference_allele","tumor_allele","consequence.transcript.transcript_id","consequence.transcript.consequence_type","consequence.transcript.aa_change","consequence.transcript.gene.symbol","consequence.transcript.is_canonical"],filters:t=>{const e={op:"and",content:[]};if(t.isoform){if("string"!=typeof t.isoform)throw".isoform value not string";e.content.push({op:"=",content:{field:"consequence.transcript.transcript_id",value:[t.isoform]}})}if(t.case_id){if("string"!=typeof t.case_id)throw".case_id value not string";e.content.push({op:"=",content:{field:"cases.case_id",value:[t.case_id]}})}if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";e.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&e.content.push(t.filter0),t.filterObj&&e.content.push((0,u.P)(t.filterObj)),e}},Z={endpoint:"/ssm_occurrences",size:1e5,fields:["ssm.ssm_id","case.case_id","case.submitter_id","case.observation.sample.tumor_sample_uuid"],filters:(t,e)=>{const n={op:"and",content:[]};if(t.ssm_id_lst){if("string"!=typeof t.ssm_id_lst)throw"ssm_id_lst not string";n.content.push({op:"=",content:{field:"ssm.ssm_id",value:t.ssm_id_lst.split(",")}})}else if(t.isoform)n.content.push({op:"=",content:{field:"ssms.consequence.transcript.transcript_id",value:[t.isoform]}});else{if(!t.isoforms)throw".ssm_id_lst, .isoform, .isoforms are all missing";if(!Array.isArray(t.isoforms))throw".isoforms[] not array";n.content.push({op:"in",content:{field:"ssms.consequence.transcript.transcript_id",value:t.isoforms}})}if(t.rglst&&(n.content.push({op:">=",content:{field:"ssms.start_position",value:t.rglst[0].start}}),n.content.push({op:"<=",content:{field:"ssms.start_position",value:t.rglst[0].stop}})),t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";n.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}if(t.filter0&&n.content.push(t.filter0),t.filterObj&&n.content.push((0,u.P)(t.filterObj)),t.tid2value)for(const r in t.tid2value){const o=e.cohort.termdb.q.termjsonByOneid(r);if(o)if("categorical"==o.type)n.content.push({op:"in",content:{field:r,value:[t.tid2value[r]]}});else if("integer"==o.type)for(const e of t.tid2value[r])n.content.push({op:e.op,content:{field:r,value:e.range}})}return n}},G="query range2variants($filters: FiltersArgument) {\n explore {\n ssms {\n hits(first: 100000, filters: $filters) {\n total\n edges {\n node {\n ssm_id\n chromosome\n start_position\n end_position\n genomic_dna_change\n\t\t\treference_allele\n tumor_allele\n occurrence {\n hits {\n total\n\t\t\t\tedges {\n\t\t\t\t node {\n\t\t\t\t case {\n\t\t\t\t\t case_id\n\t\t\t\t\t}\n\t\t\t\t }\n\t\t\t\t}\n }\n }\n\t\t\tconsequence{\n hits{\n total\n edges{\n node{\n transcript{\n transcript_id\n\t\t\t\t\t aa_change\n\t\t\t\t\t consequence_type\n\t\t\t\t\t is_canonical\n\t\t\t\t\t gene{\n\t\t\t\t\t \tsymbol\n\t\t\t\t\t }\n }\n }\n }\n }\n }\n }\n }\n }\n }\n }\n}";function U(t){if(!t.rglst)throw".rglst missing";const e=t.rglst[0];if(!e)throw".rglst[0] missing";if("string"!=typeof e.chr)throw".rglst[0].chr not string";if(!Number.isInteger(e.start))throw".rglst[0].start not integer";if(!Number.isInteger(e.stop))throw".rglst[0].stop not integer";const n={filters:{op:"and",content:[{op:"=",content:{field:"chromosome",value:[e.chr]}},{op:">=",content:{field:"start_position",value:[e.start]}},{op:"<=",content:{field:"end_position",value:[e.stop]}}]}};if(t.set_id){if("string"!=typeof t.set_id)throw".set_id value not string";n.filters.content.push({op:"in",content:{field:"cases.case_id",value:[t.set_id]}})}return t.filter0&&n.filters.content.push(t.filter0),t.filterObj&&n.filters.content.push((0,u.P)(t.filterObj)),n}},9191:(t,e,n)=>{"use strict";n.r(e),n.d(e,{client_copy:()=>J,cnvByRangeGetter_file:()=>lt,init:()=>W,snvindelByRangeGetter_bcf:()=>K,ssmIdFieldsSeparator:()=>Z,svfusionByRangeGetter_file:()=>at,validate_termdb:()=>H});var r=n(7147),o=n.n(r),i=n(4521),s=n.n(i),a=n(1017),l=n.n(a),c=n(9064),u=n(6718),f=n(5243),d=n(6452),h=n.n(d),p=n(1575),m=n(334),g=n.n(m);const y=process.env.PP_GDC_HOST\|\|"https://api.gdc.cancer.gov",v=y+(y.includes("/v0")?"":"/v0")+"/graphql",b=l().join(y,"ssm_occurrences/_mapping"),_={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}}},w=function(){const t={"case.demographic.age_at_index":{bin_size:10,first_bin_stop:30},"case.demographic.days_to_birth":{bin_size:1e3,first_bin_stop:-3e3},"case.diagnoses.circumferential_resection_margin":null,"case.demographic.days_to_death":{bin_size:1e3,first_bin_stop:1e3},"case.demographic.year_of_birth":{bin_size:10,first_bin_stop:1930},"case.demographic.year_of_death":{bin_size:5,first_bin_stop:1995},"case.diagnoses.age_at_diagnosis":{bin_size:3e3,first_bin_stop:1e4},"case.diagnoses.days_to_diagnosis":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.days_to_hiv_diagnosis":null,"case.diagnoses.days_to_last_follow_up":{bin_size:1e3,first_bin_stop:1500},"case.diagnoses.days_to_last_known_disease_status":{bin_size:500,first_bin_stop:1500},"case.diagnoses.days_to_new_event":null,"case.diagnoses.days_to_recurrence":{bin_size:100,first_bin_stop:200},"case.diagnoses.ldh_level_at_diagnosis":null,"case.diagnoses.ldh_normal_range_upper":null,"case.diagnoses.lymph_nodes_positive":null,"case.diagnoses.lymph_nodes_tested":null,"case.diagnoses.pathology_details.breslow_thickness":null,"case.diagnoses.pathology_details.circumferential_resection_margin":null,"case.diagnoses.pathology_details.greatest_tumor_dimension":null,"case.diagnoses.pathology_details.gross_tumor_weight":null,"case.diagnoses.pathology_details.lymph_nodes_positive":{bin_size:10,first_bin_stop:10},"case.diagnoses.pathology_details.lymph_nodes_tested":{bin_size:10,first_bin_stop:25},"case.diagnoses.pathology_details.number_proliferating_cells":null,"case.diagnoses.pathology_details.percent_tumor_invasion":null,"case.diagnoses.pathology_details.peripancreatic_lymph_nodes_tested":{bin_size:10,first_bin_stop:35},"case.diagnoses.pathology_details.prostatic_chips_positive_count":null,"case.diagnoses.pathology_details.prostatic_chips_total_count":null,"case.diagnoses.pathology_details.prostatic_involvement_percent":null,"case.diagnoses.pathology_details.tumor_largest_dimension_diameter":{bin_size:10,first_bin_stop:20},"case.diagnoses.peripancreatic_lymph_nodes_tested":null,"case.diagnoses.treatments.days_to_treatment_end":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.treatments.days_to_treatment_start":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.treatments.number_of_cycles":null,"case.diagnoses.treatments.treatment_dose":{bin_size:1e3,first_bin_stop:1e3},"case.diagnoses.tumor_largest_dimension_diameter":null,"case.diagnoses.year_of_diagnosis":{bin_size:10,first_bin_stop:1995},"case.exposures.alcohol_days_per_week":{bin_size:1,first_bin_stop:2},"case.exposures.bmi":null,"case.exposures.cigarettes_per_day":{bin_size:50,first_bin_stop:20},"case.exposures.height":null,"case.exposures.pack_years_smoked":{bin_size:50,first_bin_stop:40},"case.exposures.tobacco_smoking_onset_year":{bin_size:100,first_bin_stop:1998},"case.exposures.tobacco_smoking_quit_year":{bin_size:100,first_bin_stop:2e3},"case.exposures.weight":null,"case.exposures.years_smoked":{bin_size:10,first_bin_stop:30},"case.family_histories.relationship_age_at_diagnosis":null},e={};for(const n in t){const r=t[n];e[n]=r?{default:{mode:"discrete",type:"regular-bin",bin_size:r.bin_size,startinclusive:!1,stopinclusive:!0,first_bin:{startunbounded:!0,stop:r.first_bin_stop}}}:_}return e}(),x="ssm_occurrence_centrics";async function k(t){const e=new Map,n=await h()(b,{method:"GET",headers:{"Content-Type":"application/json",Accept:"application/json"}});let r;try{r=JSON.parse(n.body)}catch(t){throw"invalid JSON from GDC dictionary"}if(!r._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(r.fields))throw".fields not array";if(!Array.isArray(r.nested))throw".nested not array";const o=new Set(r.nested);let i=0,s=0,a=0,c=0,u=0,f=0;for(const t of r.fields){if(A(t)){i++;continue}const n=t.split(".");for(let t=1;t<n.length;t++){const i=n.slice(0,t).join("."),l=i+"."+n[t],f=n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),d={id:l.toLowerCase(),name:f,included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){d.isleaf=!0;const t=r._mapping[x+"."+l];t&&("keyword"==t.type?(d.type="categorical",a++):"long"==t.type?(d.type="integer",d.bins=w[d.id]\|\|JSON.parse(JSON.stringify(_)),c++):"double"==t.type?(d.type="float",d.bins=w[d.id]\|\|JSON.parse(JSON.stringify(_)),u++):console.log("GDC !!! ERR !!! Unknown variable type: "+t.type),"integer"!=d.type&&"float"!=d.type\|\|w[d.id]\|\|(console.log(`GDC !!! Lack bin config for ${d.type} ${d.id}`),await N(d.id))),d.type\|\|s++,q(d)}if(1==t);else if(d.parent_id=i,d.type){d.included_types_set.add(d.type);let t=e.get(i);for(;t&&(t.included_types_set.add(d.type),t.child_types_set.add(d.type),t.parent_id);)t=e.get(t.parent_id)}o.has(l)&&(d.isObjectList=!0),e.set(l,d)}}for(const t of e.values())t.type\|\|f++,t.included_types=[...t.included_types_set],t.child_types=[...t.child_types_set],delete t.included_types_set,delete t.child_types_set;console.log("GDC dictionary:",e.size,"total variables,",i,"lines skipped,",s,"lines with unknown term type,","categorical="+a,"integer="+c,"float="+u,"parent="+f),Object.freeze(e),function(t,e){const n=t.cohort.termdb.q={};async function r(e,n){if(0==e.length\|\|!n)return;const r=await t.termdb.termid2totalsize2.get(e.map((t=>t.id)),JSON.parse(n));for(const t of e)if(t){const e=r.get(t.id);"categorical"==t.type&&e?e.length?t.samplecount=e.map((t=>t[1])).reduce(((t,e)=>t+e)):(t.disabled=!0,t.samplecount=0):"integer"!=t.type&&"float"!=t.type\|\|(t.samplecount=e.total,0==e.total&&(t.disabled=!0))}}n.getRootTerms=async(t,n=null)=>{const o=[];for(const t of e.values())null==t.parent_id&&o.push(JSON.parse(JSON.stringify(t)));return await r(o,n),o},n.getTermChildren=async(t,n=null,o=null)=>{const i=[];for(const n of e.values())n.parent_id==t&&i.push(JSON.parse(JSON.stringify(n)));return await r(i,o),i},n.findTermByName=async(t,n=null,o,i=null,s=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const a=[];for(const n of e.values())s&&!(0,p.CG)(n,s)\|\|n.id.includes(t)&&a.push(JSON.parse(JSON.stringify(n)));return await r(a,i),a},n.getAncestorIDs=t=>{if(!e.has(t))return;const n=t.split("."),r=[];for(let t=1;t<n.length;t++)r.push(n.slice(0,t+1).join("."));return r},n.getAncestorNames=n.getAncestorIDs,n.termjsonByOneid=t=>{const n=e.get(t);return n?JSON.parse(JSON.stringify(n)):null},n.getSupportedChartTypes=()=>{const t={},n={};for(const r of e.values())r.type&&(r.cohort in t\|\|(t[r.cohort]=["barchart","table","regression"],n[r.cohort]=0),"survival"!=r.type\|\|t[r.cohort].includes("survival")\|\|t[r.cohort].push("survival"),"condition"!=r.type\|\|t[r.cohort].includes("cuminc")\|\|t[r.cohort].push("cuminc"),"float"!=r.type&&"integer"!=r.type\|\|(n[r.cohort]+=r.samplecount));for(const e in n)n[e]>0&&t[e].push("boxplot"),n[e]>1&&t[e].push("scatterplot");return t}}(t,e),t.cohort.termdb.termtypeByCohort=[],a&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),c&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),u&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),await async function(t){var e,n,r;const o={"Content-Type":"application/json",Accept:"application/json"},i={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},s=await h()(l().join(y,"files"),{method:"POST",headers:o,body:JSON.stringify(i)}),a=JSON.parse(s.body);if(t.gdcOpenProjects=new Set,null!=a&&null!==(e=a.data)&&void 0!==e&&null!==(n=e.aggregations)&&void 0!==n&&null!==(r=n["cases.project.project_id"])&&void 0!==r&&r.buckets){for(const e of a.data.aggregations["cases.project.project_id"].buckets)e.key&&t.gdcOpenProjects.add(e.key);console.log("GDC open-access projects:",t.gdcOpenProjects.size)}else console.log("getting open project_id but return is not re.data.aggregations['cases.project.project_id'].buckets")}(t),async function(){try{await M(y+"/ssms"),await M(y+"/ssm_occurrences"),await M(y+"/cases"),await M(y+"/files"),await M(y+"/analysis/top_mutated_genes_by_project"),await async function(t){const e=new Date;try{const e="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}}";await h().post(t,{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({query:e,variables:{}})})}catch(e){throw"gdc api down: "+t}console.log("GDC GraphQL API okay: "+t,new Date-e,"ms")}(v)}catch(t){console.error(`\n##########################################\n#\n# GDC API unavailable\n# ${y}\n# ${v}\n#\n##########################################`)}}(),async function(t){t.aliquot2submitter={cache:new Map,get:async e=>t.aliquot2submitter.cache.has(e)?t.aliquot2submitter.cache.get(e):e},t.map2caseid={cache:new Map,get:e=>t.map2caseid.cache.get(e)};try{if(g().features.stopGdcCacheAliquot)return console.log("GDC aliquot2submitter not cached!");const e=await T(t,1,0);if(!Number.isInteger(e))throw"gdc totalCases not integer";const n=new Date;console.log("GDC: Start to cache sample IDs of",e,"cases...");const r=1e3;for(let n=0;n<Math.ceil(e/r);n++)await T(t,r,1e3n);console.log("GDC: Done caching sample IDs",Math.ceil((new Date-n)/1e3),"s"),console.log("\t",t.aliquot2submitter.cache.size,"aliquot IDs to sample submitter id"),console.log("\t",t.map2caseid.cache.size,"different ids to case uuid.")}catch(t){console.log("Error at caching: "+t)}}(t)}function q(t){"case.diagnoses.age_at_diagnosis"!=t.id\|\|(t.printDays2years=!0)}async function N(t){const e=t.replace("case.","").replace(".","__"),n=`\n\t query ContinuousAggregationQuery($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 ${e} {\n\t\t\t stats {\n\t\t\t\t\tMin : min\n\t\t\t\t\tMax: max\n\t\t\t\t\tMean: avg\n\t\t\t\t\tSD: std_deviation\n\t\t\t\t\tcount\n\t\t\t\t}\n\t\t\t\trange(ranges: $filters2) {\n\t\t\t\t buckets {\n\t\t\t\t\tdoc_count\n\t\t\t\t\tkey\n\t\t\t\t }\n\t\t\t\t}\n\t\t\t }\n\t\t\t}\n\t\t }\n\t\t}\n\t }\n\t}`,r={caseFilters:{},filters:{},filters2:{op:"range",content:[{ranges:[{from:0,to:1}]}]}};try{const o=await h().post(v,{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({query:n,variables:r})}),i=JSON.parse(o.body).data.viewer.explore.cases.aggregations[e].stats;console.log(`${t} Min=${i.Min} Max=${i.Max} Mean=${i.Mean} Median=${i.Median} SD=${i.SD} Count=${i.count}`)}catch(e){console.log(`${t} ??? ERR ???`)}}const S=new Set(["case.consent_type","case.days_to_consent","case.days_to_index"]);function A(t){return!!(t.startsWith("ssm")\|\|t.startsWith("case.observation")\|\|t.startsWith("case.available_variation_data"))\|\|(!(!t.endsWith("_id")\|\|t.endsWith("project_id"))\|\|(!!S.has(t)\|\|void 0))}async function M(t){try{const e=new Date;await h()(t),console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){throw"gdc api down: "+t}}async function T(t,e,n,r){var o,i,s;const a=["fields=submitter_id,samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(r)a.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+r+'"]}}]}');else{if(!Number.isInteger(e)\|\|!Number.isInteger(n))throw"size and from not integers";a.push("size="+e),a.push("from="+n)}const l=await h()(y+"/cases?"+a.join("&")),c=JSON.parse(l.body);if(!Array.isArray(null==c\|\|null===(o=c.data)\|\|void 0===o?void 0:o.hits))throw"re.data.hits[] not array";for(const e of c.data.hits){const n=e.id;if(!n)throw"h.id (case uuid) missing";const r=e.submitter_id;if(!r)throw"h.submitter_id missing";if(t.map2caseid.cache.set(r,n),Array.isArray(e.samples))for(const r of e.samples){const e=r.submitter_id;if(!e)throw"sample.submitter_id missing";if(t.map2caseid.cache.set(e,n),Array.isArray(r.portions))for(const o of r.portions)if(Array.isArray(o.analytes))for(const r of o.analytes)if(Array.isArray(r.aliquots))for(const o of r.aliquots){const r=o.aliquot_id;if(!r)throw"aliquot.aliquot_id missing";t.aliquot2submitter.cache.set(r,e),t.map2caseid.cache.set(r,n)}}}return null===(i=c.data)\|\|void 0===i\|\|null===(s=i.pagination)\|\|void 0===s?void 0:s.total}var C=n(817),j=n(3856),O=n(3625),E=n(7027),R=n(478),I=n(2273),P=n(2852),F=n(394),L=n(1711),D=n(1883),z=n(2188),B=n(2974),$=n(3795);const Z=".",G="Ancestry_PC_",U="Unannotated";async function W(t,e,n,r=null,i=null){var s,a;await H(t),t.queries&&(await async function(t,e){const n=t.queries.snvindel;if(!n)return;if(n.url){if(!n.url.base)throw".snvindel.url.base missing";if(!n.url.key)throw".snvindel.url.key missing"}if(!n.byisoform&&!n.byrange)throw"byisoform and byrange are both missing on queries.snvindel";if(n.byrange)if(n.byrange.gdcapi)f.validate_query_snvindel_byrange(t);else if(n.byrange.bcffile){var r;n.byrange.bcffile=n.byrange.bcffile.startsWith(g().tpmasterdir)?n.byrange.bcffile:l().join(g().tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await K(t,e),null!==(r=n.byrange._tk)&&void 0!==r&&r.samples.length\|\|delete n.byrange._tk.samples,Q(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}else{if(!n.byrange.chr2bcffile)throw"unknown query method for queries.snvindel.byrange";n.byrange._tk={chr2files:{}};for(const t in n.byrange.chr2bcffile)n.byrange._tk.chr2files[t]={file:l().join(g().tpmasterdir,n.byrange.chr2bcffile[t])};delete n.byrange.chr2bcffile,n.byrange.get=await K(t,e),n.byrange._tk.samples.length\|\|delete n.byrange._tk.samples,Q(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";f.validate_query_snvindel_byisoform(t)}if(n.m2csq){if(!n.m2csq.by)throw".by missing from queries.snvindel.m2csq";if("ssm_id"!=n.m2csq.by)throw"unknown value of queries.snvindel.m2csq.by";if(!n.m2csq.gdcapi)throw"unknown query method for queries.snvindel.m2csq";f.validate_m2csq(t)}}(t,e),await async function(t,e){const n=t.queries.svfusion;if(!n)return;if(!n.byrange)throw"byrange missing from queries.svfusion";if(n.byrange){if(!n.byrange.file)throw"unknown query method for svfusion.byrange";n.byrange.file=n.byrange.file.startsWith(g().tpmasterdir)?n.byrange.file:l().join(g().tpmasterdir,n.byrange.file),n.byrange.get=await at(t,e),Q(t,n.byrange.samples,"svfusion.byrange")}}(t,e),await async function(t,e){const n=t.queries.geneCnv;if(!n)return;if(!n.bygene)throw"geneCnv.bygene missing";n.bygene.gdcapi&&f.validate_query_geneCnv2(t)}(t),await async function(t,e){const n=t.queries.cnv;if(!n)return;if(!n.byrange)throw"byrange missing from queries.cnv";if(n.byrange){if(!n.byrange.file)throw"unknown query method for cnv.byrange";n.byrange.file=n.byrange.file.startsWith(g().tpmasterdir)?n.byrange.file:l().join(g().tpmasterdir,n.byrange.file),n.byrange.get=await lt(t,e),Q(t,n.byrange.samples,"cnv.byrange")}}(t,e),await async function(t,e){const n=t.queries.ld;if(!n)return;if(!Array.isArray(n.tracks)\|\|!n.tracks.length)throw"ld.tracks[] not nonempty array";for(const t of n.tracks){if(!t.name)throw"name missing from one of ld.tracks[]";if(!t.file)throw".file missing from one of ld.tracks[]";t.file0=t.file,t.file=l().join(g().tpmasterdir,t.file),await j.validate_tabixfile(t.file),t.nochr=await j.tabix_is_nochr(t.file,null,e)}if(!n.overlay)throw"ld.overlay{} missing";if(!n.overlay.color_0)throw"ld.overlay.color_0 missing";if(!n.overlay.color_1)throw"ld.overlay.color_1 missing"}(t,e),await async function(t,e){const n=t.queries.geneExpression;if(!n)return;if(n.gdcapi)return void f.validate_query_geneExpression(t);if(!n.file)throw".file missing from queries.geneExpression";n.file=l().join(g().tpmasterdir,n.file),await j.validate_tabixfile(n.file),n.nochr=await j.tabix_is_nochr(n.file,null,e);{const t=await j.get_header_tabix(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}Q(t,n.samples,"geneExpression"),n.get=async r=>{const o=await nt(r,n.samples,t);if(0==(null==o?void 0:o.size))return new Map;const i=new Map;for(const t of r.genes)if(t.gene\|\|(t.gene=t.name),t.gene){if(!t.chr){const n=e.genedb.getjsonbyname.all(t.gene);if(0==n.length)continue;const r=JSON.parse(n.find((t=>t.isdefault)).genemodel\|\|n[0].genemodel);t.start=r.start,t.stop=r.stop,t.chr=r.chr}i.set(t.gene,{}),await j.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:e=>{const n=e.split("\t");let r;try{r=JSON.parse(n[3])}catch(t){return}r.gene.toLowerCase()==t.gene.toLowerCase()&&(o&&!o.has(r.sample)\|\|(i.get(t.gene)[r.sample]=r.value))}})}return i}}(t,e),await async function(t,e){const n=t.queries.singleSampleMutation;if(!n)return;if(n.gdcapi)f.validate_query_singleSampleMutation(t,e);else{if(!n.folder)throw"unknown query method for singleSampleMutation";n.get=async e=>{var r,o,i;let s=e;if(null!==(r=t.cohort)&&void 0!==r&&null!==(o=r.termdb)&&void 0!==o&&null!==(i=o.q)&&void 0!==i&&i.sampleName2id&&(s=t.cohort.termdb.q.sampleName2id(e),null==s))return[];const a=await j.read_file(l().join(g().tpmasterdir,n.folder,s.toString()));return JSON.parse(a)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGenomeQuantification;if(!n)return;for(const r in n){if(!Number.isFinite(n[r].min))throw"min not a number";if(!Number.isFinite(n[r].max))throw"max not a number";if(n[r].min>=n[r].max)throw"min>=max";if(!n[r].folder)throw"unknown query method for singleSampleGenomeQuantification";n[r].get=async(o,i)=>{var s,a,c;let u=o;if(null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.termdb)&&void 0!==a&&null!==(c=a.q)&&void 0!==c&&c.sampleName2id&&(u=t.cohort.termdb.q.sampleName2id(o),null==u))return[];return await st(l().join(g().tpmasterdir,n[r].folder,u.toString()),e,n[r],i)}}}(t,e),await async function(t,e){const n=t.queries.singleSampleGbtk;if(!n)return;for(const e in n){if(!Number.isFinite(n[e].min))throw"min not a number";if(!Number.isFinite(n[e].max))throw"max not a number";if(n[e].min>=n[e].max)throw"min>=max";if(!n[e].folder)throw"unknown query method for singleSampleGbtk";n[e].get=async r=>{var i,s,a;let c=r;if(null!==(i=t.cohort)&&void 0!==i&&null!==(s=i.termdb)&&void 0!==s&&null!==(a=s.q)&&void 0!==a&&a.sampleName2id&&(c=t.cohort.termdb.q.sampleName2id(r),null==c))return{};const u=l().join(n[e].folder,c+".gz");try{return await o().promises.stat(l().join(g().tpmasterdir,u)),{path:u}}catch(t){return{}}}}}(t),await async function(t,e){const n=t.queries.probe2cnv;if(!n)return;if(n.file)n.file=l().join(g().tpmasterdir,n.file),await j.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on probe2cnv";n.dir=await j.cache_index(n.url,n.indexURL)}n.nochr=await j.tabix_is_nochr(n.file\|\|n.url,null,e);{const e=await j.get_header_tabix(n.file);if(!e[0])throw"header line missing from "+n.file;const r=e[0].split("\t");if(r.length<3)throw"probe2cnv header line less than 3 fields";n.samples=r.slice(2).map((e=>({name:t.cohort.termdb.q.sampleName2id(e)})))}n.get=async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";if(e.cnvGainCutoff&&!Number.isFinite(e.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(e.cnvLossCutoff&&!Number.isFinite(e.cnvLossCutoff))throw"cnvLossCutoff is not finite";const r=[];{const o=await nt(e,n.samples,t);if(o){if(0==o.size)return[];for(const[t,e]of n.samples.entries())o.has(e.name)?r.push([]):r.push(null)}else for(const t of n.samples)r.push([])}for(const t of e.rglst)await j.get_lines_bigfile({args:[n.file,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:t=>{const e=t.split("\t");for(const[t,n]of r.entries()){if(!n)continue;const r=Number(e[t+2]);Number.isFinite(r)&&n.push(r)}}});const o=[];for(const[t,i]of r.entries()){if(!i)continue;const r=(0,E.Z)(i,50),s={dt:I.dtcnv,value:r,samples:[{sample_id:n.samples[t].name}]};r>0&&r>(e.cnvGainCutoff\|\|.1)?s.class=I.mclasscnvgain:r<0&&r<(e.cnvLossCutoff\|\|-.1)&&(s.class=I.mclasscnvloss),s.class&&o.push(s)}return o}}(t,e),(0,C.uK)(t),function(t){if(!t.ssm2canonicalisoform)return;if(t.ssm2canonicalisoform.gdcapi)return void f.validate_ssm2canonicalisoform(t.ssm2canonicalisoform);throw"ssm2canonicalisoform.gdcapi is false"}(t),function(t,e){if(!e.genedb.hasTable_refseq2ensembl)return;t.refseq2ensembl_query=e.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?")}(t,e),function(t,e){if(!t.queries.snvindel&&!t.queries.svfusion&&!t.queries.geneCnv)return;t.mayGetGeneVariantData=async(n,r)=>{if("object"!=typeof n.term)throw"tw.term{} is not object";if("geneVariant"!=n.term.type)throw"tw.term.type is not geneVariant";if("string"!=typeof n.term.name)throw"tw.term.name is not string";if(!n.term.name)throw"tw.term.name should be gene symbol but is empty string";const o=[];if("snp"==n.term.subtype){var i;if(null===(i=t.queries.snvindel)\|\|void 0===i\|\|!i.allowSNPs)throw"snvindel does not allow snp";const a=(await ft(t,n.term,e,r)).find((t=>n.term.alleles.includes(t.ref)&&n.term.alleles.includes(t.alt)));if(a){const t=[];for(const e of a.samples){var s;if(null===(s=e.formatK2v)\|\|void 0===s\|\|!s.GT)continue;const n=[];for(const t of e.formatK2v.GT.split("/"))0==t?n.push(a.ref):1==t?n.push(a.alt):console.log("unknown allele idx");n.join("/"),n.join("/");t.push({sample_id:e.sample_id,GT:n.join("/")})}const e={samples:t};o.push(e)}}else{if(t.queries.snvindel){const i=await ft(t,n.term,e,r);o.push(...i)}if(t.queries.svfusion){const i=await async function(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,sessionid:r.sessionid};if(t.queries.svfusion.byrange)return await ut(e,n),o.rglst=[e],await t.queries.svfusion.byrange.get(o);throw"unknown queries.svfusion method"}(t,n.term,e,r);o.push(...i)}if(t.queries.cnv){const i=await async function(t,e,n,r){var o,i,s;const a={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,cnvMaxLength:null==e\|\|null===(o=e.q)\|\|void 0===o?void 0:o.cnvMaxLength,cnvGainCutoff:null==e\|\|null===(i=e.q)\|\|void 0===i?void 0:i.cnvGainCutoff,cnvLossCutoff:null==e\|\|null===(s=e.q)\|\|void 0===s?void 0:s.cnvLossCutoff,sessionid:r.sessionid};if(t.queries.cnv.byrange)return await ut(e.term,n),a.rglst=[e.term],await t.queries.cnv.byrange.get(a);throw"unknown queries.cnv method"}(t,n,e,r);o.push(...i)}if(t.queries.geneCnv){const e=await async function(t,e,n,r){const o={filter0:r.filter0,sessionid:r.sessionid};if(t.queries.geneCnv.bygene)return e.name?(o.gene=e.name,await t.queries.geneCnv.bygene.get(o)):[];throw"unknown queries.geneCnv method"}(t,n.term,0,r);o.push(...e)}}const a=new Map;for(const e of o)if(Array.isArray(e.samples))for(const r of e.samples){var l,c;if(a.has(r.sample_id)\|\|a.set(r.sample_id,{sample:r.sample_id}),null!==(l=t.cohort)&&void 0!==l&&null!==(c=l.termdb)&&void 0!==c&&c.additionalSampleAttributes)for(const e of t.cohort.termdb.additionalSampleAttributes)e in r&&(a.get(r.sample_id)[e]=r[e]);a.get(r.sample_id)[n.term.name]\|\|(a.get(r.sample_id)[n.term.name]={key:n.term.name,label:n.term.name,values:[]});const o={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,_SAMPLEID_:r.sample_id,_SAMPLENAME_:r.sample_id};if(r.__sampleName&&(o._SAMPLENAME_=r.__sampleName),"value"in e&&(o.value=e.value),r.formatK2v)for(const t in r.formatK2v)o[t]=r.formatK2v[t];e.dt==I.dtsnvindel?r.GT&&(o.value=r.GT,o.key=r.GT):e.dt!=I.dtfusionrna&&e.dt!=I.dtsv\|\|(o.pairlst=e.pairlst),t.cohort.termdb.q.id2sampleName&&Number.isInteger(r.sample_id)&&(o._SAMPLENAME_=t.cohort.termdb.q.id2sampleName(r.sample_id)),a.get(r.sample_id)[n.term.name].values.push(o)}return await async function(t,e,n,r){var o;if(null===(o=e.assayAvailability)\|\|void 0===o\|\|!o.byDt)return;const i=t.filter?new Set((await(0,P.get_samples)(t.filter,e)).map((t=>t.id))):null;for(const t in e.assayAvailability.byDt){const o=e.assayAvailability.byDt[t];if(o.byOrigin)for(const e in o.byOrigin){ct(t,o.byOrigin[e],n,r,e,i)}else ct(t,o,n,r,!1,i)}}(r,t,a,n.term.name),a}}(t,e)),function(t){if(!t.assayAvailability)return;if(t.assayAvailability.byDt)for(const e in t.assayAvailability.byDt){const n=t.assayAvailability.byDt[e];if(n.byOrigin)for(const e in n.byOrigin){const r=n.byOrigin[e];if(!r.yes\|\|!r.no\|\|!r.term_id)throw"ds.assayAvailability.byDt..byOrigin properties require .term_id .yes{} .no{}";dt(t,r)}else{if(!n.yes\|\|!n.no\|\|!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";dt(t,n)}}}(t),function(t){if(!t.viewModes)return;if(!Array.isArray(t.viewModes))throw"ds.viewModes[] not array";for(const r of t.viewModes)if(r.byInfo){var e,n;if(null==t\|\|null===(e=t.queries)\|\|void 0===e\|\|null===(n=e.snvindel)\|\|void 0===n\|\|!n.info)throw"view mode byInfo but queries.snvindel.info missing";const o=t.queries.snvindel.info[r.byInfo];if(!o)throw"unknown INFO field for viewmode byInfo";if("Float"!=o.Type&&"Integer"!=o.Type)throw"viewmode byInfo Type is not numeric";r.type="numeric",r.label=r.byInfo}else if(!r.byAttribute)throw"view mode not byInfo or byAttribute"}(t),null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.db)&&void 0!==a&&a.refresh&&r&&(0,D.setDbRefreshRoute)(t,r,i)}function J(t){var e;const n={isMds3:!0,label:t.label};if(t.viewModes&&(n.skewerModes=t.viewModes),function(t,e){if(!t.queries)return;const n={};t.queries.singleSampleMutation&&(n.singleSampleMutation={sample_id_key:t.queries.singleSampleMutation.sample_id_key,discoSkipChrM:t.queries.singleSampleMutation.discoSkipChrM});if(t.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const e in t.queries.singleSampleGenomeQuantification)n.singleSampleGenomeQuantification[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGenomeQuantification[e])),delete n.singleSampleGenomeQuantification[e].folder}if(t.queries.singleSampleGbtk){n.singleSampleGbtk={};for(const e in t.queries.singleSampleGbtk)n.singleSampleGbtk[e]=JSON.parse(JSON.stringify(t.queries.singleSampleGbtk[e])),delete n.singleSampleGbtk[e].folder}const r=t.queries.snvindel;r&&(e.has_skewer=!0,n.snvindel={forTrack:r.forTrack,vcfid4skewerName:r.vcfid4skewerName,variantUrl:r.variantUrl,skewerRim:r.skewerRim},r.m2csq&&(n.snvindel.m2csq={by:r.m2csq.by}),r.info&&(e.bcf={info:r.info}),r.format&&(e.bcf\|\|(e.bcf={}),e.bcf.format=r.format));if(t.queries.ld){n.ld=JSON.parse(JSON.stringify(t.queries.ld));for(const t of n.ld.tracks)delete t.file}e.queries=n}(t,n),null!==(e=t.cohort)&&void 0!==e&&e.termdb&&(n.termdb={},t.cohort.termdb.allowCaseDetails&&(n.termdb.allowCaseDetails={sample_id_key:t.cohort.termdb.allowCaseDetails.sample_id_key})),t.variant2samples){const e=t.variant2samples;n.variant2samples={sunburst_twLst:e.sunburst_twLst,twLst:e.twLst,type_samples:e.type_samples,type_summary:e.type_summary,type_sunburst:e.type_sunburst,url:e.url,variantkey:e.variantkey}}return n}async function H(t){var e,r,o,i;if(t.cohort){if(!t.cohort.termdb)throw"ds.cohort is set but cohort.termdb{} missing";if(!t.cohort.db)throw"ds.cohort is set but cohort.db{} missing";if(!t.cohort.db.file&&!t.cohort.db.file_fullpath)throw"ds.cohort.db.file missing"}else{if(!t.termdb)return;t.cohort={},t.cohort.termdb=t.termdb,delete t.termdb}const s=t.cohort.termdb;if(null!=s&&null!==(e=s.dictionary)&&void 0!==e&&e.gdcapi)await k(t);else if(null!=s&&null!==(r=s.dictionary)&&void 0!==r&&r.dbFile)t.cohort.db={file:s.dictionary.dbFile},delete s.dictionary.dbFile,(0,F.server_init_db_queries)(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";(0,F.server_init_db_queries)(t)}if(s.termid2totalsize2&&(s.termid2totalsize2.gdcapi,s.termid2totalsize2.get=async(e,n={},r=null)=>s.termid2totalsize2.gdcapi?await f.get_termlst2size(e,n,r,t):await async function(t,e,n,r){const o=Y(e,r),i=new Map;for(const e of t)if(e.term&&"categorical"==e.term.type){var s,a;const t={term1_id:e.id,term1_q:{type:"values"},filter:o},n=await(0,L.barchart_data)(t,r,r.cohort.termdb);if(null==n\|\|null===(s=n.data)\|\|void 0===s\|\|null===(a=s.charts)\|\|void 0===a\|\|!a[0])continue;const l=[];for(const t of n.data.charts[0].serieses)l.push([t.seriesId,t.total]);i.set(e.id,l)}return n?[i,n]:i}(e,n,r,t)),function(t){const e=t.selectCohort;if(!e)return;if("object"!=typeof e)throw"selectCohort{} not object";if(!e.term)throw"term{} missing from termdb.selectCohort";if(!e.term.id)throw"id missing from termdb.selectCohort.term";if("string"!=typeof e.term.id)throw"termdb.selectCohort.term.id is not string";if("categorical"!=e.term.type)throw'type is not hardcoded "categorical" from termdb.selectCohort.term';{const n=t.q.termjsonByOneid(e.term.id);if(!n)throw"termdb.selectCohort.term.id is invalid";if("categorical"!=n.type)throw"termdb.selectCohort.term type is not categorical"}if(!e.values)throw"values[] missing from termdb.selectCohort";if(!Array.isArray(e.values))throw"termdb.selectCohort.values is not array";if(0==e.values.length)throw"termdb.selectCohort.values[] cannot be empty";for(const t of e.values){if(!t.keys)throw"keys[] missing from one of selectCohort.values[]";if(!Array.isArray(t.keys))throw"keys[] is not array from one of selectCohort.values[]";if(0==t.keys.length)throw"keys[] is empty from one of selectCohort.values[]"}}(s),await async function(t){if(!t.restrictAncestries)return;if(!Array.isArray(t.restrictAncestries)\|\|0==t.restrictAncestries.length)throw"termdb.restrictAncestries[] is not non-empty array";for(const e of t.restrictAncestries){if(!e.name)throw"name missing from one of restrictAncestries";if("object"!=typeof e.tvs)throw".tvs{} missing from one of restrictAncestries";if(!e.tvs.term)throw"tvs.term{} missing from an ancestry";if(!e.tvs.term.id)throw"tvs.term.id missing from an ancestry";{const n=t.q.termjsonByOneid(e.tvs.term.id);if(!n)throw"tvs.term.id is invalid from an ancestry";if("categorical"!=n.type)throw"tvs.term.type is not categorical from an ancestry"}if(!Number.isInteger(e.PCcount))throw"PCcount is not integer";if(e.PCfile)e.pcs=await V(e.PCfile,e.PCcount);else if(e.PCfileBySubcohort){if(!t.selectCohort)throw"PCfileBySubcohort is in use but selectCohort is not enabled";for(const n in e.PCfileBySubcohort){let r=!0;for(const e of t.selectCohort.values)if(n==e.keys.sort().join(",")){r=!1;break}if(r)throw"unknown subcohort from PCfileBySubcohort";const o=e.PCfileBySubcohort[n];if(!o.file)throw".file missing for a subcohort in PCfileBySubcohort";o.pcs=await V(o.file,e.PCcount)}}}}(s),await(0,z.wz)(t),await(0,B.mayInitiateMatrixplots)(t),"minTimeSinceDx"in s){if(!Number.isFinite(s.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(s.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in s){if(!Number.isFinite(s.ageEndOffset))throw"termdb.ageEndOffset not number";if(s.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(t.cohort.termdb.additionalSampleAttributes){if(!Array.isArray(t.cohort.termdb.additionalSampleAttributes))throw"termdb.additionalSampleAttributes not array";for(const e of t.cohort.termdb.additionalSampleAttributes)if("string"!=typeof e)throw"non-str key in termdb.additionalSampleAttributes[]"}if(s.convertSampleId){if(!s.convertSampleId.gdcapi)throw"unknown implementation of tdb.convertSampleId";f.convertSampleId_addGetter(s,t)}if(null!==(o=t.cohort)&&void 0!==o&&null!==(i=o.db)&&void 0!==i&&i.connection){t.sampleName2Id=new Map,t.sampleId2Name=new Map;const e="SELECT * FROM sampleidmap",n=t.cohort.db.connection.prepare(e).all();for(const e of n)t.sampleId2Name.set(e.id,e.name),t.sampleName2Id.set(e.name,e.id);t.getSampleIdMap=e=>{const n={};for(const r in e)n[r]=t.sampleId2Name.get(+r);return n}}if(t.cohort.mutationset){const{mayGetGeneVariantData:e,getTermTypes:r,mayGetMatchingGeneNames:o}=n(7833);t.mayGetGeneVariantData=e,t.getTermTypes=r,t.mayGetMatchingGeneNames=o}}async function V(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(G+t,new Map);let r=0;for(const o of(await j.read_file(l().join(g().tpmasterdir,t))).trim().split("\n")){r++;const t=o.split("\t"),i=Number(t[0]);if(!Number.isInteger(i))throw"non-integer sample id from a line of restrictAncestries pc file";for(let r=1;r<=e;r++){const e=G+r,o=Number(t[r]);if(Number.isNaN(o))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(i,o)}}return console.log(r,"samples loaded from "+t),Object.freeze(n)}function Y(t,e){const n=[];if(t.filterObj&&n.push(t.filterObj),t.tid2value&&n.push(rt(t.tid2value,e)),0!=n.length)return 1==n.length?n[0]:(0,R.filterJoin)(n)}function Q(t,e,n){var r;if(!e)return;let o;if(null!=t&&null!==(r=t.cohort)&&void 0!==r&&r.termdb){for(const t of e){const e=Number(t.name);if(!Number.isInteger(e))throw"non-integer sample id from "+n;t.name=e}o=", all integer IDs"}console.log(e.length,"samples from "+n+" of "+t.label+o)}async function K(t,e){var n;const r=t.queries.snvindel.byrange;if(r._tk.file)await j.init_one_vcf(r._tk,e,!0);else if(r._tk.chr2files){let t;for(const n in r._tk.chr2files){if("chr17"!=n)continue;const o=r._tk.chr2files[n];try{await j.init_one_vcf(o,e,!0);const i=JSON.stringify(o.samples);if(t){if(i!=t)throw"Different samples found in bcf file of "+n}else t=i,r._tk.samples=o.samples,r._tk.format=o.format,r._tk.info=o.info,r._tk.nochr=o.nochr}catch(t){console.log("missing file ignored:",o.file)}}}if(null!==(n=r._tk)&&void 0!==n&&n.samples.length){if(!r._tk.format)throw"bcf file has samples but no FORMAT"}else if(r._tk.format)throw"bcf file has FORMAT but no samples";if(r._tk.format){for(const t in r._tk.format)"GT"==t&&(r._tk.format[t].isGT=!0);if(t.queries.snvindel.format4filters){if(!Array.isArray(t.queries.snvindel.format4filters))throw"snvindel.format4filters[] is not array";for(const e of t.queries.snvindel.format4filters)r._tk.format[e]&&(r._tk.format[e].isFilter=!0);delete t.queries.snvindel.format4filters}}if(r._tk.info){if(r.infoFields){for(const t of r.infoFields){if(!t.key)throw".key missing from one of snvindel.byrange.infoFields[]";t.name\|\|(t.name=t.key);const e=r._tk.info[t.key];if(!e)throw"invalid key from one of snvindel.byrange.infoFields[]";e.categories=t.categories,e.name=t.name,e.separator=t.separator}delete r.infoFields}if(t.queries.snvindel.infoUrl){for(const e of t.queries.snvindel.infoUrl){const t=r._tk.info[e.key];if(!t)throw"invalid key from one of snvindel.infoUrl[]";t.urlBase=e.base}delete t.queries.snvindel.infoUrl}}return t.queries.snvindel.info=r._tk.info,t.queries.snvindel.format=r._tk.format,async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";const n=X(e);let o;if(r._tk.chr2files){const t=r._tk.chr2files[e.rglst[0].chr];if(!t)throw"unknown chr for chr2files";o=t.file}else o=r._tk.file\|\|r._tk.url;const i=["query",o,"-r",e.rglst.map((t=>(r._tk.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+(t.stop+1))).join(","),"-f","%ID\t%CHROM\t%POS\t%REF\t%ALT\t%INFO\t%FORMAT\n"],s=await nt(e,r._tk.samples,t);if(s){if(0==s.size)return[];i.push("-s",[...s].join(","))}e.variantFilter&&(0,$.add_bcf_variant_filter)(e.variantFilter,i);const a=[];return await j.get_lines_bigfile({isbcf:!0,args:i,dir:r._tk.dir,callback:o=>{const i=o.split("\t"),l=i[0],c=i[1],u=Number(i[2]),f=i[3],d=i[4].split(","),h=i[5],p={pos:u-1};(0,O.compute_mclass)(r._tk,f,d,p,h,l,e.isoform);for(const o of p.mlst){var m,g,y;e.hiddenmclass&&e.hiddenmclass.has(o.class)\|\|(tt(o,e)\|\|p.mlst.length>1&&null!==(m=e.variantFilter)&&void 0!==m&&m.lst&&et(o,e)\|\|(o.chr=(r._tk.nochr?"chr":"")+c,o.ssm_id=[o.chr,o.pos,o.ref,o.alt].join(Z),null!==(g=r._tk)&&void 0!==g&&null!==(y=g.samples)&&void 0!==y&&y.length&&(ot(r,o,i,e.addFormatValues,t,s,n),!o.samples)\|\|a.push(o)))}}}),a}}function X(t){var e,n;const r=t.formatFilter\|\|{};return"format"==(null===(e=t.skewerRim)\|\|void 0===e?void 0:e.type)&&null!==(n=t.skewerRim.hiddenvalues)&&void 0!==n&&n.size&&(r[t.skewerRim.formatKey]=t.skewerRim.hiddenvalues),Object.keys(r).length?r:void 0}function tt(t,e){if(!e.infoFilter)return!1;for(const n in e.infoFilter){const r=t.info[n];if(r)if(Array.isArray(r)){for(const t of e.infoFilter[n])if(r.includes(t))return!0}else if(e.infoFilter[n].includes(r))return!0}return!1}function et(t,e){for(const r of e.variantFilter.lst){const e=t.info[r.tvs.term.id];if(null==e)return!0;if("integer"==r.tvs.term.type\|\|"float"==r.tvs.term.type){var n;const t=Number(e);if(Number.isNaN(t))return!0;const o=null===(n=r.tvs.ranges)\|\|void 0===n?void 0:n[0];if(o){if("start"in o)if(o.startinclusive){if(t<o.start)return!0}else if(t<=o.start)return!0;if("stop"in o)if(o.stopinclusive){if(t>o.stop)return!0}else if(t>=o.stop)return!0}}}return!1}async function nt(t,e,n){if(!e)return;const r=function(t,e){{const e=t.filter\|\|t.filterObj;if(e){if(!Array.isArray(e.lst))throw"filterObj.lst is not array";return 0==e.lst.length?null:e}}if(t.tid2value){if("object"!=typeof t.tid2value)throw"q.tid2value{} not object";return rt(t.tid2value,e)}}(t,n);if(!r)return;const o=[...new Set((await(0,P.get_samples)(r,n)).map((t=>t.id)))],i=new Set(e.map((t=>t.name))),s=new Set;for(const t of o)i.has(t)&&s.add(t);return s}function rt(t,e){const n={type:"tvslst",in:!0,join:"and",lst:[]};for(const r in t){const o=e.cohort.termdb.q.termjsonByOneid(r);if(!o)continue;const i=t[r];n.lst.push({type:"tvs",tvs:{term:o,values:[{key:i}]}})}return n}function ot(t,e,n,r,o,i,s){if(!n[6]\|\|"."==n[6])return;const a=[];for(const e of n[6].split(":")){const n=t._tk.format[e];if(!n)throw"invalid format field: "+n;a.push(n)}const l=[];let c=t._tk.samples;i&&(c=[...i].map((t=>({name:t}))));for(const[t,e]of c.entries()){const o=n[t+7];if(!o\|\|"."==o)continue;const i=it(o.split(":"),a,e,r);if(i){if(s){let t=!1;for(const e in s){const n=e in i.formatK2v?i.formatK2v[e]:U;if(s[e].has(n)){t=!0;break}}if(t)continue}l.push(i)}}l.length&&(e.samples=l)}function it(t,e,n,r){const o={};for(const[n,r]of e.entries()){const e=t[n];if(e&&"."!=e)if(r.isGT){if("./."==e\|\|".\|."==e)continue;o.GT=e}else o[r.ID]=e}if(0==Object.keys(o).length)return null;const i={sample_id:n.name};return r&&(i.formatK2v=o),i}function st(t,e,n,r=1){r=Number(r);const i=200,a=20;let l=0;for(const t in e.majorchr)l+=e.majorchr[t];const f=800/l,d={};let h=0;const p=[];for(const t in e.majorchr){const n=e.majorchr[t];d[t]=(0,c.Z)().domain([0,n]).range([fh,f(h+n)]),h+=n,p.push({chr:t,chrLen:n,xStart:f(h-n),xStop:fh})}const m=(0,c.Z)().domain([n.min,n.max]).range([i,0]),g=(0,u.createCanvas)(890r,240r),y=g.getContext("2d");r>1&&y.scale(r,r),b(n.max),b(0),b(n.min);const v=s().createInterface({input:o().createReadStream(t)});return new Promise(((t,r)=>{v.on("line",(t=>{const e=t.split("\t"),r=e[0];if(!r)return;if(!d[r])return;const o=Number(e[1]);if(!Number.isInteger(o))return;const i=Number(e[2]);if(!Number.isFinite(i))return;if(i<n.min\|\|i>n.max)return;y.fillStyle=i>0?n.positiveColor:n.negativeColor;const s=d[r](o),l=a+m(i);y.fillRect(70+s,l,1,1)})),v.on("close",(()=>{!function(){y.strokeStyle="black",y.beginPath();{const t=220-m(0);y.moveTo(70,t),y.lineTo(870,t),y.stroke()}let t=!0;y.fillStyle="black",y.font="12px Arial",y.textAlign="center";for(const n in d){if(y.fillText(n.replace("chr",""),70+d[n](e.majorchr[n]/2),234),t){t=!1;continue}const 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r=X(e),o=await nt(e,n.samples,t);if(0==(null==o?void 0:o.size))return[];const i=new Map;for(const t of e.rglst)await j.get_lines_bigfile({args:[n.file\|\|n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const s=n.split("\t"),a=Number(s[1]);let l,c,u,f,d;try{l=JSON.parse(s[3])}catch(t){return}if(l.dt!=I.dtfusionrna&&l.dt!=I.dtsv)return;if(l.class=l.dt==I.dtsv?I.mclasssv:I.mclassfusionrna,e.hiddenmclass&&e.hiddenmclass.has(l.class))return;if(l.sample&&o&&!o.has(l.sample))return;if(l.chrA)c=1,u=l.geneA\|\|l.chrA,f=l.strandA,d=[{a:{chr:l.chrA,pos:l.posA,strand:l.strandA,name:l.geneA},b:{chr:t.chr,pos:a,strand:l.strandB,name:l.geneB}}];else if(l.chrB)c=0,u=l.geneB\|\|l.chrB,f=l.strandB,d=[{a:{chr:t.chr,pos:a,strand:l.strandA,name:l.geneA},b:{chr:l.chrB,pos:l.posB,strand:l.strandB,name:l.geneB}}];else{if(!l.pairlst)throw"missing chrA and chrB";{d=l.pairlst;const t=l.pairlst.findIndex((t=>t.chr==chr&&t.pos==a));if(-1==t)throw"current point missing from pairlst";c=t}}const h=[l.dt,t.chr,a,f,c,encodeURIComponent(u)].join(Z);let p;if(l.sample&&(p={sample_id:l.sample},l.mattr)){if(r)for(const t in r){const e=t in l.mattr?l.mattr[t]:U;if(r[t].has(e))return}e.addFormatValues&&(p.formatK2v=l.mattr)}i.has(h)\|\|i.set(h,{ssm_id:h,dt:l.dt,class:l.class,chr:t.chr,pos:a,strand:f,pairlstIdx:c,mname:u,pairlst:d,samples:[]}),p&&i.get(h).samples.push(p)}});return[...i.values()]}}async function lt(t,e){const n=t.queries.cnv.byrange;if(n.file)await j.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on cnv.byrange{}";n.dir=await j.cache_index(n.url,n.indexURL)}n.nochr=await j.tabix_is_nochr(n.file\|\|n.url,null,e);{const t=await j.get_header_tabix(n.file);if(!t[0])throw"header line missing from "+n.file;const e=t[0].split(" ");if("#sample"!=e[0])throw"header line not starting with #sample: "+n.file;n.samples=e.slice(1).map((t=>({name:t})))}return async e=>{if(!Array.isArray(e.rglst))throw"q.rglst[] is not array";if(0==e.rglst.length)throw"q.rglst[] blank array";if(e.cnvMaxLength&&!Number.isInteger(e.cnvMaxLength))throw"cnvMaxLength is not integer";if(e.cnvGainCutoff&&!Number.isFinite(e.cnvGainCutoff))throw"cnvGainCutoff is not finite";if(e.cnvLossCutoff&&!Number.isFinite(e.cnvLossCutoff))throw"cnvLossCutoff is not finite";const r=X(e),o=await nt(e,n.samples,t);if(0==(null==o?void 0:o.size))return[];const i=[],s=[];for(const t of e.rglst)s.push(j.get_lines_bigfile({args:[n.file\|\|n.url,(n.nochr?t.chr.replace("chr",""):t.chr)+":"+t.start+"-"+t.stop],dir:n.dir,callback:n=>{const s=n.split("\t"),a=Number(s[1]),l=Number(s[2]);if(e.cnvMaxLength&&l-a>=e.cnvMaxLength)return;let c;try{c=JSON.parse(s[3])}catch(t){return}if(c.dt==I.dtcnv){if(c.start=a,c.stop=l,Number.isFinite(c.value)){if(c.value>0&&e.cnvGainCutoff&&c.value<e.cnvGainCutoff)return;if(c.value<0&&e.cnvLossCutoff&&c.value>e.cnvLossCutoff)return;c.class=c.value>0?I.mclasscnvgain:I.mclasscnvloss}else if(c.class!=I.mclasscnvgain&&c.class!=I.mclasscnvloss)return;if(c.ssm_id=[t.chr,c.start,c.stop,c.class].join(Z),(!e.hiddenmclass\|\|!e.hiddenmclass.has(c.class))&&(!c.sample\|\|!o\|\|o.has(c.sample))){if(c.sample){const t={sample_id:c.sample};if(c.mattr){if(r)for(const t in r){const e=t in c.mattr?c.mattr[t]:U;if(r[t].has(e))return}e.addFormatValues&&(t.formatK2v=c.mattr)}delete c.sample,c.samples=[t]}i.push(c)}}}}));return await Promise.all(s),i}}function ct(t,e,n,r,o,i){for(const s of e.yesSamples){if(i&&!i.has(s))continue;n.has(s)\|\|n.set(s,{sample:s});const e=n.get(s);r in e\|\|(e[r]={key:r,values:[],label:r}),o?e[r].values.some((e=>e.dt==t&&e.origin==o))\|\|e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:s,origin:o}):e[r].values.some((e=>e.dt==t))\|\|e[r].values.push({dt:Number.parseInt(t),class:"WT",_SAMPLEID_:s})}for(const s of e.noSamples){if(i&&!i.has(s))continue;n.has(s)\|\|n.set(s,{sample:s});const e=n.get(s);r in e\|\|(e[r]={key:r,values:[],label:r}),o?e[r].values.some((e=>e.dt==t&&e.origin==o))\|\|e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:s,origin:o}):e[r].values.some((e=>e.dt==t))\|\|e[r].values.push({dt:Number.parseInt(t),class:"Blank",_SAMPLEID_:s})}}async function ut(t,e){if(t.chr&&Number.isInteger(t.start)&&Number.isInteger(t.stop))return;if(!t.name)throw"both term.name and term.chr/start/stop missing";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)throw"unknown gene name";const r=n.find((t=>t.isdefault))\|\|n[0],o=JSON.parse(r.genemodel);if(!o.chr\|\|!Number.isInteger(o.start)\|\|!Number.isInteger(o.stop))throw"invalid chr/start/stop from returned gm";t.chr=o.chr,t.start=o.start,t.stop=o.stop}async function ft(t,e,n,r){const o={addFormatValues:!0,filter0:r.filter0,filterObj:r.filter,sessionid:r.sessionid};if(t.queries.geneCnv&&(o.useCaseid4sample=!0),t.queries.snvindel.byisoform)return await async function(t,e){if(t.isoform&&"string"==typeof t.isoform)return;if(!t.name)throw"both term.name and term.isoform";const n=e.genedb.getjsonbyname.all(t.name);if(0==n.length)return;const r=n.find((t=>t.isdefault))\|\|n[0],o=JSON.parse(r.genemodel);if(!o.isoform)throw"isoform missing from returned gm";t.isoform=o.isoform}(e,n),e.isoform?(o.isoform=e.isoform,await t.queries.snvindel.byisoform.get(o)):[];if(t.queries.snvindel.byrange)return await ut(e,n),o.rglst=[e],await t.queries.snvindel.byrange.get(o);throw"unknown queries.snvindel method"}function dt(t,e){e.yesSamples=new Set,e.noSamples=new Set;const n=`SELECT sample, value\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = '${e.term_id}'`,r=t.cohort.db.connection.prepare(n).all();for(const t of r)e.yes.value.includes(t.value)?e.yesSamples.add(t.sample):e.no.value.includes(t.value)&&e.noSamples.add(t.sample)}},8089:(t,e,n)=>{"use strict";n.d(e,{f:()=>u});var r=n(3856);const o=n(9699),i=n(7147),s=n(1017),a=n(2081).spawn,l=n(334),c=n(9191).snvindelByRangeGetter_bcf;n(1271).run_rust;function u(t){return async(e,n)=>{try{if(!e.query.genome)throw".genome missing";const i=t[e.query.genome];if(!i)throw"invalid genome";const s=function(t,e){const n=t.query;t.get("X-Auth-Token")&&(n.token=t.get("X-Auth-Token"));(0,r.mayCopyFromCookie)(n,t.cookies),n.hiddenmclasslst&&(n.hiddenmclass=new Set(n.hiddenmclasslst.split(",")),delete n.hiddenmclasslst);return n}(e),a=await async function(t,e){if(t.dslabel){if(!e.datasets)throw".datasets{} missing from genome";const n=e.datasets[t.dslabel];if(!n)throw"invalid dslabel";return n}const n={queries:{}};if(t.bcffile\|\|t.bcfurl){const[r,i,s]=o.fileurl({query:{file:t.bcffile,url:t.bcfurl}});if(r)throw r;const a={};s?(a.url=i,a.indexURL=t.bcfindexURL):a.file=i,n.queries.snvindel={byrange:{_tk:a}},n.queries.snvindel.byrange.get=await c(n,e)}return n}(s,i);!function(t,e){var n;if(t.filter0){const n="object"==typeof t.filter0?t.filter0:JSON.parse("string"==typeof t.filter0&&t.filter0.startsWith("%")?decodeURIComponent(t.filter0):t.filter0);t.filter0=e.validate_filter0(n)}t.filterObj&&"string"==typeof t.filterObj&&(t.filterObj=JSON.parse("string"==typeof t.filterObj&&t.filterObj.startsWith("%")?decodeURIComponent(t.filterObj):t.filterObj));if(t.skewerRim){if("format"!=t.skewerRim.type)throw"unknown skewerRim.type";var r,o;if(!t.skewerRim.formatKey)throw"skewerRim.formatKey missing when type=format";if(null===(r=e.queries)\|\|void 0===r\|\|null===(o=r.snvindel)\|\|void 0===o\|\|!o.format)throw"snvindel.format{} not found when type=format";if(!e.queries.snvindel.format[t.skewerRim.formatKey])throw"invalid skewerRim.formatKey";if(t.skewerRim.hiddenvalues=new Set,t.skewerRim.hiddenvaluelst){if(!Array.isArray(t.skewerRim.hiddenvaluelst))throw"query.skewerRim.hiddenvaluelst is not array";for(const e of t.skewerRim.hiddenvaluelst)t.skewerRim.hiddenvalues.add(e);delete t.skewerRim.hiddenvaluelst}}if(t.formatFilter){var i,s;if("object"!=typeof t.formatFilter)throw"formatFilter{} not object";if(null===(i=e.queries)\|\|void 0===i\|\|null===(s=i.snvindel)\|\|void 0===s\|\|!s.format)throw"snvindel.format{} not found when formatFilter is used";const n={};for(const r in t.formatFilter){if(!e.queries.snvindel.format[r])throw"invalid format key from formatFilter";if(!Array.isArray(t.formatFilter[r]))throw"formatFilter[k] value is not array";n[r]=new Set(t.formatFilter[r])}t.formatFilter=n}("format"==(null===(n=t.skewerRim)\|\|void 0===n?void 0:n.type)\|\|t.formatFilter)&&(t.addFormatValues=!0)}(s,a);const l=await async function(t,e){if(t.singleSampleMutation){var n;if(null===(n=e.queries.singleSampleMutation)\|\|void 0===n\|\|!n.get)throw"not supported on this dataset";return{mlst:await e.queries.singleSampleMutation.get(t.singleSampleMutation,t)}}if(t.singleSampleGenomeQuantification){if(!e.queries.singleSampleGenomeQuantification)throw"not supported on this dataset";const n=e.queries.singleSampleGenomeQuantification[t.singleSampleGenomeQuantification.dataType];if(!n)throw"invalid dataType";return await n.get(t.singleSampleGenomeQuantification.sample,t.devicePixelRatio)}if(t.singleSampleGbtk){if(!e.queries.singleSampleGbtk)throw"not supported on this dataset";const n=e.queries.singleSampleGbtk[t.singleSampleGbtk.dataType];if(!n)throw"invalid dataType";return await n.get(t.singleSampleGbtk.sample)}if(t.ssm2canonicalisoform){if(!e.ssm2canonicalisoform)throw"ssm2canonicalisoform not supported on this dataset";return{isoform:await e.ssm2canonicalisoform.get(t)}}if(t.variant2samples){if(!e.variant2samples)throw"not supported by server";return{variant2samples:await e.variant2samples.get(t)}}if(t.m2csq){if(e.queries&&e.queries.snvindel&&e.queries.snvindel.m2csq)return{csq:await e.queries.snvindel.m2csq.get(t)};throw"m2csq not supported on this dataset"}if(t.forTrack){const n={};if(t.skewer){if(n.skewer=[],e.queries.snvindel){const r=await async function(t,e){if(t.isoform){if(t.atgenomic){if(!e.queries.snvindel.byrange)throw".atgenomic but missing byrange query method";return await e.queries.snvindel.byrange.get(t)}if(e.queries.snvindel.byisoform)return await e.queries.snvindel.byisoform.get(t)}if(t.rglst){if(!e.queries.snvindel.byrange)throw"q.rglst[] provided but .byrange{} is missing";return await e.queries.snvindel.byrange.get(t)}throw"insufficient query parameters for snvindel"}(t,e);n.skewer.push(...r)}if(e.queries.svfusion){const r=await async function(t,e){if(t.rglst){if(!e.queries.svfusion.byrange)throw"q.rglst provided but svfusion.byrange missing";return await e.queries.svfusion.byrange.get(t)}throw"insufficient query parameters for svfusion"}(t,e);n.skewer.push(...r)}if(e.queries.geneCnv){const r=await async function(t,e){if(t.gene){if(!e.queries.geneCnv.bygene)throw"q.gene provided but geneCnv.bygene missing";return await e.queries.geneCnv.bygene.get(t)}}(t,e);n.geneCnv=r}!function(t,e){if(e.skewer){const 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n={rglst:[{chr:t.chr,start:t.start,stop:t.stop}],addFormatValues:!0,variantFilter:t.variantFilter},[r,o]=t.details.groups;if("filter"==r.type&&"filter"==(null==o?void 0:o.type)){n.filterObj=c(t,r.filter);const i=l(await e.queries.snvindel.byrange.get(n));n.filterObj=c(t,o.filter);const s=l(await e.queries.snvindel.byrange.get(n)),u=function(t,e,n){const[r,o]=n.details.groups,i=[];for(const n of t){n.groupData=[{refCount:n._refCount,altCount:n._altCount}];const t=e.find((t=>t.chr==n.chr&&t.pos==n.pos&&t.ref==n.ref&&t.alt==n.alt));t?n.groupData.push({refCount:t._refCount,altCount:t._altCount}):n.groupData.push({refCount:0,altCount:0}),i.push(n)}for(const n of e){t.find((t=>t.chr==n.chr&&t.pos==n.pos&&t.ref==n.ref&&t.alt==n.alt))\|\|(n.groupData=[{refCount:0,altCount:0},{refCount:n._refCount,altCount:n._altCount}],i.push(n))}return i}(i.mlst,s.mlst,t);return{mlst:u,totalSampleCount_group1:a(i.mlst),totalSampleCount_group2:a(s.mlst)}}n.filterObj=c(t);const i=await 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i=t.queries.snvindel.populations.find((t=>t.key==r.key));if(!i)throw"invalid group.key for population";const s=new Set;for(const t of n)for(const e of t.samples)s.add(e.sample_id);const a=new Map;let l=0;for(const e of i.sets){const n={infokey_AC:e.infokey_AC,infokey_AN:e.infokey_AN,average:0},r=await o({ds:t,key:e.key});for(const t of r){if(!s.has(t.sample))continue;const e=Number(t.value);Number.isFinite(e)&&(n.average+=e,l+=e)}a.set(e.key,n)}for(const[t,e]of a)e.average/=l;return a}(t,e,n);for(const o of n)o.groupData=h(t,e,o,r);const i=e.groupTestMethods[e.groupTestMethodsIdx];if(!i)throw"details.groupTestMethodsIdx out of bound";switch(i.name){case"Allele frequency difference":return void d(t,e,n);case"Fisher's exact test":return void await m(n);default:throw"unknown value from groupTestMethods[]"}}(t,e,n);d(t,e,n)}(n,t.details,i.mlst)}for(const t of i.mlst)delete t.samples,delete t._altCount,delete t._refCount;e.send(i)}function a(t){const e=new Set;for(const n of t)if(n.samples)for(const t of n.samples)e.add(t.sample_id);return e.size}function l(t){const e={mlst:[],skipMcountWithoutAlt:0};for(const n of t){const[t,r]=f(n);0!=t?(n._altCount=t,n._refCount=r-t,e.mlst.push(n)):e.skipMcountWithoutAlt++}return e}function c(t,e){const n=[t.filter];if(e)n.push(e);else for(const e of t.details.groups)"filter"==e.type&&n.push(e.filter);return r(n)}function u(t,e,n){if("filter"!=n.type)if("info"!=n.type){if("population"!=n.type)throw"unknown type of single group";{const r=t.queries.snvindel.populations.find((t=>t.key==n.key));if(!r)throw"unknown population";for(const t of e){let e=0,n=0;for(const o of r.sets)e+=Number(t.info[o.infokey_AC]\|\|0),n+=Number(t.info[o.infokey_AN]\|\|0);t.nm_axis_value=e/n}}}else{if(!n.infoKey)throw"infoKey missing on single group.type=info";for(const t of e){const e=t.info[n.infoKey];if(null==e);else{const n=Number(e);Number.isNaN(n)\|\|(t.nm_axis_value=n)}}}else for(const t of e)t.nm_axis_value=Number((t._altCount/(t._altCount+t._refCount)).toPrecision(2))}function f(t){let e=0,n=0;for(const o of t.samples){var r;if(null==o\|\|null===(r=o.formatK2v)\|\|void 0===r\|\|!r.GT)continue;const i=o.formatK2v.GT.split("/").map(Number);n+=i.length;for(const n of i)n==t.altAlleleIdx&&e++}return[e,n]}function d(t,e,n){const[r,o]=e.groups;u(t,n,r);const i=n.map((t=>t.nm_axis_value));u(t,n,o);for(const[t,e]of n.entries())e.nm_axis_value=i[t]-e.nm_axis_value}function h(t,e,n,r){const o=[];for(const i of e.groups)if("info"!=i.type)if("filter"!=i.type){if("population"!=i.type)throw"unknown group.type";{if(!i.key)throw"group.key missing for type=population";const e=t.queries.snvindel.populations.find((t=>t.key==i.key));if(!e)throw"invalid group.key for population";const s=new Map;for(const t of e.sets)s.set(t.key,{ACraw:Number(n.info[t.infokey_AC]\|\|0),ANraw:Number(n.info[t.infokey_AN]\|\|0)});let a=0,l=0;if(i.adjust_race)[a,l]=p(s,r);else for(const t of 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t)0==n.p_value&&(n.nm_axis_value=Math.max(50,e))}},817:(t,e,n)=>{"use strict";n.d(e,{uK:()=>f,z9:()=>d});const{stratinput:r}=n(1881),{querySamples_gdcapi:o}=n(5243),{get_densityplot:i}=n(9402),{ssmIdFieldsSeparator:s}=n(9191),{dtfusionrna:a,dtsv:l}=(n(3856),n(2273)),c=n(4065),{getSampleData_dictionaryTerms_termdb:u}=n(2974);function f(t){const e=t.variant2samples;if(e){if(e.type_samples="samples",e.type_sunburst="sunburst",e.type_summary="summary",!e.variantkey)throw".variantkey missing from variant2samples";if(-1==["ssm_id"].indexOf(e.variantkey))throw"invalid value of variantkey";if(e.twLst){if(!Array.isArray(e.twLst))throw"variant2samples.twLst[] is not array";if(0==e.twLst.length)throw"variant2samples.twLst[] empty array";if(!t.cohort\|\|!t.cohort.termdb)throw"ds.cohort.termdb missing when variant2samples.twLst is in use";for(const n of e.twLst){if(!n.id)throw"tw.id missing from one of variant2samples.twLst[]";const e=t.cohort.termdb.q.termjsonByOneid(n.id);if(!e)throw"term not found for one of variant2samples.twLst: "+n.id;if(n.term=e,!n.q)throw"tw.q{} missing for one of variant2samples.twLst: "+n.id}}if(e.sunburst_twLst){if(!Array.isArray(e.sunburst_twLst))throw".sunburst_twLst[] not array from variant2samples";if(0==e.sunburst_twLst.length)throw".sunburst_twLst[] empty array from variant2samples";if(!t.cohort\|\|!t.cohort.termdb)throw"ds.cohort.termdb missing when variant2samples.sunburst_twLst is in use";for(const n of e.sunburst_twLst){if(!n.id)throw"tw.id missing from one of variant2samples.sunburst_twLst[]";const e=t.cohort.termdb.q.termjsonByOneid(n.id);if(!e)throw"term not found for one of variant2samples.sunburst_twLst: "+n.id;if(n.term=e,!n.q)throw"tw.q{} missing for one of variant2samples.sunburst_twLst: "+n.id}}if(e.gdcapi);else{var n,f,g,y,v,b,_;let e=!1;if(null!==(n=t.queries)&&void 0!==n&&null!==(f=n.snvindel)&&void 0!==f&&null!==(g=f.byrange)&&void 0!==g&&null!==(y=g._tk)&&void 0!==y&&y.samples&&(e=!0),null!==(v=t.queries)&&void 0!==v&&null!==(b=v.svfusion)&&void 0!==b&&null!==(_=b.byrange)&&void 0!==_&&_.samples&&(e=!0),!e)throw"cannot find a sample source from ds.queries{}"}if(e.get=async e=>await async function(t,e){!function(t,e){if("samples"==t.get){var n,r;const o=null===(n=e.queries)\|\|void 0===n\|\|null===(r=n.snvindel)\|\|void 0===r?void 0:r.byrange;o&&(o.bcffile\|\|o.chr2bcffile)&&o._tk.format&&(t.addFormatValues=!0)}}(t,e);const n=await async function(t,e){var n;const r=t.twLst?t.twLst.slice():[];if(e.variant2samples.gdcapi)return await o(t,r,e,t.geneTwLst);if(t.ssm_id_lst)return await async function(t,e,n){const r=new Map;for(const e of t.ssm_id_lst.split(",")){const o=e.split(s);if(4!=o.length){if(6!=o.length)throw"unknown format of ssm id";{if(!n.queries.svfusion\|\|!n.queries.svfusion.byrange)throw"queries.svfusion.byrange missing when id has 6 fields";const[e,i,s,c,u,f]=o,h=decodeURIComponent(f),p=Number(e);if(p!=l&&p!=a)throw"dt not sv/fusion";const m=Number(s);if(Number.isNaN(m))throw"position not integer";const g=Number(u);if(Number.isNaN(g))throw"pairlstIdx not integer";const y=Object.assign({},t,{rglst:[{chr:i,start:m,stop:m+1}]}),v=await n.queries.svfusion.byrange.get(y);for(const t of v)t.dt==p&&t.pos==m&&t.strand==c&&t.pairlstIdx==g&&t.mname==h&&d(t.samples,r,t.ssm_id)}}else{if(!n.queries.snvindel\|\|!n.queries.snvindel.byrange)throw"queries.snvindel.byrange missing when id has 4 fields";const[e,i,s,a]=o,l=Number(i);if(Number.isNaN(l))throw"no integer position for snvindel from ssm id";const c=Object.assign({},t,{rglst:[{chr:e,start:l,stop:l}]}),u=await n.queries.snvindel.byrange.get(c);for(const t of u)t.pos==l&&t.ref==s&&t.alt==a&&d(t.samples,r,t.ssm_id)}}return h(r,e,n),[...r.values()]}(t,r,e);if(t.rglst)return await p(t,r,e);if(t.geneTwLst){if("object"!=typeof t.genome)throw"serverside genome obj needed";t.rglst=[];for(const e of t.geneTwLst)if(e.term.chr&&e.term.start&&e.term.stop)t.rglst.push({chr:e.term.chr,start:e.term.start,stop:e.term.stop});else{const n=c.getResult(t.genome,{deep:1,input:e.term.name});if(n.gmlst){const e=n.gmlst[0];t.rglst.push({chr:e.chr,start:e.start,stop:e.stop})}}const n=await p(t,r,e);return delete t.rglst,n}if(null==e\|\|null===(n=e.cohort)\|\|void 0===n\|\|!n.termdb)throw"unable to do sql query: .cohort.termdb missing for ds";const i={ds:e,filter:t.filter\|\|t.filterObj},f=await u(i,t.twLst),m=[];for(const e in f.samples){const n=f.samples[e];n.sample_id=n.sample,delete n.sample;for(const e of t.twLst)n[e.term.id]&&(n[e.term.id]=n[e.term.id].key);m.push(n)}return m}(t,e);if(t.get==e.variant2samples.type_samples){var f,g,y;return!t.useIntegerSampleId&&null!=e&&null!==(f=e.cohort)&&void 0!==f&&null!==(g=f.termdb)&&void 0!==g&&null!==(y=g.q)&&void 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e.cohort.termdb.termid2totalsize2.get([t[0]],r);for(const[t,n]of o.get(c)){const r=e.cohort.termdb.useLower?t.toLowerCase():t;l?(a.get(c).add(r),s.push({count:n,id0:c,v0:r})):a.get(c).has(r)&&s.push({count:n,id0:c,v0:r})}}const u=null==t\|\|null===(o=t[1])\|\|void 0===o?void 0:o.id;if(u){const r=[];for(const o of a.get(c)){const i={tid2value:{[c]:o}};n.filterObj&&(i.filterObj=n.filterObj),r.push(e.cohort.termdb.termid2totalsize2.get([t[1]],i,o))}const o=await Promise.all(r);for(const[t,n]of o)for(const[r,o]of t.get(u)){const t=e.cohort.termdb.useLower?r.toLowerCase():r;l?(a.get(u).add(t),s.push({count:o,id0:c,v0:n,id1:u,v1:t})):a.get(u).has(t)&&s.push({count:o,id0:c,v0:n,id1:u,v1:t})}}const f=null==t\|\|null===(i=t[2])\|\|void 0===i?void 0:i.id;if(f){const r=[];for(const o of a.get(c))for(const i of a.get(u)){const s={tid2value:{[c]:o,[u]:i}};n.filterObj&&(s.filterObj=n.filterObj),r.push(e.cohort.termdb.termid2totalsize2.get([t[2]],s,{v0:o,v1:i}))}const o=await Promise.all(r);for(const[t,n]of o)for(const[t,r]of v2counts.get(f)){const o=e.cohort.termdb.useLower?t.toLowerCase():t;l?(a.get(f).add(o),s.push({count:r,id0:c,v0:n.v0,id1:u,v1:n.v1,id2:f,v2:o})):a.get(f).has(o)&&s.push({count:r,id0:c,v0:n.v0,id1:u,v1:n.v1,id2:f,v2:o})}}return s}(n.twLst,e,n,s);await async function(t,e,n){for(const r of t){if(!r.id0)continue;if(!r.v0)continue;const t=n.cohort.termdb.useLower?r.v0.toLowerCase():r.v0;if(!r.id1){const n=e.find((e=>null==e.id1&&e.v0==t));n&&(r.cohortsize=n.count);continue}if(!r.v1)continue;const o=n.cohort.termdb.useLower?r.v1.toLowerCase():r.v1;if(!r.id2){const n=e.find((e=>null==e.id2&&e.v0==t&&e.v1==o));n&&(r.cohortsize=n.count);continue}if(!r.v2)continue;const i=n.cohort.termdb.useLower?r.v2.toLowerCase():r.v2;if(!r.id3){const e=crosstabL2.find((e=>e.v0==t&&e.v1==o&&e.v2==i));e&&(r.cohortsize=e.count)}}}(s,t,e)}return s}(n,e,t);if(t.get==e.variant2samples.type_summary){const r=await async function(t,e,n){if(!n.twLst)throw"q.twLst[] missing for make_summary()";const r=[];for(const e of n.twLst)if(e.term)if("categorical"==e.term.type){const n=m(t,e.id);r.push({termid:e.id,termname:e.term.name,numbycategory:[...n].sort(((t,e)=>e[1]-t[1]))})}else{if("integer"!=e.term.type&&"float"!=e.term.type)throw"unknown term type";{const n=await i(e.term,t);r.push({termid:e.id,termname:e.term.name,density_data:n})}}if(e.cohort.termdb.termid2totalsize2){const t=await e.cohort.termdb.termid2totalsize2.get(n.twLst,n);for(const{termid:e,numbycategory:n}of r){if(!n)continue;const r=t.get(e);if(r)for(const t of n){const e=r.find((e=>e[0].toLowerCase()==t[0].toLowerCase()));e&&t.push(e[1])}}}return r}(n,e,t);return r}throw"unknown get type"}(e,t),e.url&&!e.url.base)throw".variant2samples.url.base missing"}}function d(t,e,n){for(const r of t){e.has(r.sample_id)\|\|(r.ssm_id_lst=[],r.formatK2v&&(r.ssmid2format={}),e.set(r.sample_id,r));const t=e.get(r.sample_id);t.ssm_id_lst.push(n),t.ssmid2format&&(t.ssmid2format[n]=r.formatK2v)}}function h(t,e,n){if(e)for(const r of t.values())for(const t of e){const e=n.cohort.termdb.q.getSample2value(t.id,r.sample_id);e[0]&&(r[t.id]=e[0].value)}}async function p(t,e,n){const r=new Map;if(n.queries.snvindel){const e=await n.queries.snvindel.byrange.get(t);for(const t of e)d(t.samples,r,t.ssm_id)}if(n.queries.svfusion){const e=await n.queries.svfusion.byrange.get(t);for(const t of e)d(t.samples,r,t.ssm_id)}return h(r,e,n),[...r.values()]}function m(t,e){const n=new Map;if("sample_id"in t[0]){for(const r of t){const t=r[e];t&&(n.has(t)\|\|n.set(t,new Set),n.get(t).add(r.sample_id))}const r=new Map;for(const[t,e]of n)r.set(t,e.size);return r}if("case_uuid"in t[0]){for(const r of t){const t=r[e];t&&(n.has(t)\|\|n.set(t,new Set),n.get(t).add(r.case_uuid))}const r=new Map;for(const[t,e]of n)r.set(t,e.size);return r}for(const e of t){const t=e[term.id];t&&n.set(t,1+(n.get(t)\|\|0))}return n}},5728:(t,e)=>{function n(t,e,n){const r=[];for(const o of t){const t=new Map,i=[];for(const r of o.samples){const o=n.sample2term.get(r);if(o){const n=o.get(e);null==n?i.push(r):(t.has(n)\|\|t.set(n,[]),t.get(n).push(r))}else i.push(r)}const s=[...t].sort(((t,e)=>e[1].length-t[1].length));for(const t of s){const e={value:t[0],samples:t[1],children:[]};r.push(e),o.children&&o.children.push(e)}if(i.length){const t={isgap:!0,samples:i,children:[]};r.push(t),o.children&&o.children.push(t)}}return r}e.g=t=>{!function(t){if(!t.sample2term)throw".sample2term missing";if(!t.terms)throw".terms[] missing";if(!t.config)throw".config{} missing"}(t);const e=function(t){const e=new Map;for(const n of t.sample2term.values())for(const t of n.keys())e.set(t,1+(e.get(t)\|\|0));if(t.config.termidorder){const n=[];for(const r of t.config.termidorder){const t=e.get(r);null!=t&&n.push({id:r,samplecount:t})}return 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0!==r&&r.startsWith("container")&&Object.assign(u,{port:3e3,tpmasterdir:"/home/root/pp/tp",cachedir:"/home/root/pp/cache",hicstraw:"/home/root/pp/tools/straw",bigwigsummary:"/home/root/pp/tools/bigWigSummary",bigBedToBed:"/home/root/pp/tools/bigBedToBed",bigBedNamedItems:"/home/root/pp/tools/bigBedNamedItems",bigBedInfo:"/home/root/pp/tools/bigBedInfo"}),u.features\|\|(u.features={}),!u.backend_only&&o.existsSync(i.join(process.cwd(),"./public"))){const t=i.join(u.binpath,"cards");u.cards\|\|(u.cards={target:t,path:"cards"});const e=u.cards,n=i.join(process.cwd(),"./public/",e.path);let r;try{r=o.lstatSync(n)}catch(t){r=!1}!e.path\|\|o.existsSync(n)\|\|r\|\|(e.target\|\|(e.target=t),o.symlink(u.cards.target,n,"dir",console.error))}if(o.existsSync("./public/rev.txt")){const t=o.readFileSync("./public/rev.txt",{encoding:"utf8"}).trim().split(" ")[1];t&&(u.commitHash=t)}if(o.existsSync("./package.json")){const t=o.readFileSync("./package.json",{encoding:"utf8"});u.version=JSON.parse(t).version}t.exports=u},7395:(t,e,n)=>{const r=n(9699),o=n(7147),i=n(4521),s=n(502),a=n(7346),l=n(6778),c=n(3856),{schemeCategory10:u}=n(895),{schemeCategory20:f}=n(4052);function d(t){const e=t.toString(16);return 1==e.length?"0"+e:e}function h(t,e,n){return d(t)+d(e)+d(n)}function p(t){if(!t.cellfile)throw"cellfile missing";{const[e,n,o]=r.fileurl({query:{file:t.cellfile}});if(e)throw"cellfile error: "+e;t.cellfile=n}if(!t.delimiter)throw"delimiter missing";if(!Number.isInteger(t.barcodecolumnidx))throw"barcodecolumnidx missing";if(!Number.isInteger(t.categorycolumnidx))throw"categorycolumnidx missing";return new Promise(((e,n)=>{const r=new Map,s=i.createInterface({input:o.createReadStream(t.cellfile)});let a=!0;s.on("line",(e=>{if(a)return void(a=!1);const 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n=t.getpcd.gene_expression;if(!n.file)throw"gene_expression.file missing";{const[t,e,o]=r.fileurl({query:{file:n.file}});if(t)throw t;n.file=e}if(!Number.isInteger(n.barcodecolumnidx))throw"gene_expression.barcodecolumnidx missing";if(!n.chr)throw"gene_expression.chr missing";if(!n.start)throw"gene_expression.start missing";if(!n.stop)throw"gene_expression.stop missing";if(!n.genename)throw"gene_expression.genename missing";if(!n.autoscale)throw"gene_expression: unknown scaling method";if(!n.color_min)throw"gene_expression.color_min missing at autoscale";if(!n.color_max)throw"gene_expression.color_max missing at autoscale";const o=(n.nochr?n.chr.replace("chr",""):n.chr)+":"+n.start+"-"+n.stop,i=new Map;d=new Map;let s=0,u=0;if(e.numbercellwithgeneexp=0,e.numbercelltotal=0,await c.get_lines_bigfile({args:[n.file,o],callback:t=>{const 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0:u.events,t.term1_q);q.length&&p.sort(((t,e)=>q.indexOf(t.label)-q.indexOf(e.label)));e.send({lst:p,orderedLabels:q})}(s,n,C,T,S);if(s.getpercentile)return async function(t,e,n){const r=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!r)throw"invalid termid";if("float"!=r.type&&"integer"!=r.type)throw"not numerical term";const i=t.getpercentile,s=[],a=[],l=await f.get_rows_by_one_key({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null});for(const{value:t}of l)r.values&&r.values[t]&&r.values[t].uncomputable\|\|r.skip0forPercentile&&0==t\|\|a.push(Number(t));for(const t of i){const e=(0,o.Z)(a,t);s.push(e)}e.send({values:s})}(s,n,T);if(s.getdescrstats)return async function(t,e,n){const i=n.cohort.termdb.q.termjsonByOneid(t.tid);if(!i)throw"invalid termid";if("float"!=i.type&&"integer"!=i.type)throw"not numerical term";const s=await f.get_rows_by_one_key({ds:n,key:t.tid,filter:t.filter?"string"==typeof t.filter?JSON.parse(t.filter):t.filter:null}),a=[];for(const{value:e}of s){var l,c;i.values&&i.values[e]&&i.values[e].uncomputable\|\|("log"===(null===(l=t.settings)\|\|void 0===l\|\|null===(c=l.violin)\|\|void 0===c?void 0:c.unit)&&0===e\|\|a.push(Number(e)))}const u=a.length,d=a.reduce(((t,e)=>t+e),0)/u,h=(0,o.Z)(a,25),p=(0,o.Z)(a,50),m=(0,o.Z)(a,75),g=a.map((t=>(t-d)*2)).reduce(((t,e)=>t+e),0)/(a.length-1),y=Math.sqrt(g),v=Math.min(...a),b=Math.max(...a);e.send({values:[{id:"total",label:"n",value:u},{id:"min",label:"Minimum",value:(0,r.Z)(v,2)},{id:"p25",label:"1st quartile",value:(0,r.Z)(h,2)},{id:"median",label:"Median",value:(0,r.Z)(p,2)},{id:"mean",label:"Mean",value:(0,r.Z)(d,2)},{id:"p75",label:"3rd quartile",value:(0,r.Z)(m,2)},{id:"max",label:"Maximum",value:(0,r.Z)(b,2)},{id:"sd",label:"Standard deviation",value:(0,r.Z)(y,2)}]})}(s,n,T);if(s.getnumericcategories)return await async function(t,e,n,r){if(!t.tid)throw".tid missing";n.q.termjsonByOneid(t.tid);const o={ds:r,term_id:t.tid};t.filter&&(o.filter=t.filter);const i=await f.get_summary_numericcategories(o);e.send({lst:i})}(s,n,C,T);if(s.default_rootterm)return await async function(t,e,n){const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"";e.send({lst:await n.q.getRootTerms(r,o)})}(s,n,C);if(s.get_children)return await async function(t,e,n){if(!t.tid)throw"no parent term id";const r=t.cohortValues?t.cohortValues:"",o=t.treeFilter?t.treeFilter:"",i=await n.q.getTermChildren(t.tid,r,o);e.send({lst:i.map(A)})}(s,n,C);if(s.findterm)return await async function(t,e,n,r,o){const i={equals:[],startsWith:[],startsWord:[],includes:[]},s=decodeURIComponent(t.findterm).toUpperCase(),a=[];try{if("snp"==t.targetType){var u,f;if(null===(u=r.queries)\|\|void 0===u\|\|null===(f=u.snvindel)\|\|void 0===f\|\|!f.allowSNPs)throw"this dataset does not support snp search";const t=await(0,c.searchSNP)({byName:!0,lst:[s.toLowerCase()]},o);for(const e of t)a.push({type:"geneVariant",name:e.name,subtype:"snp",chr:e.chrom,start:e.chromStart,stop:e.chromEnd,alleles:e.alleles})}else{var d;const e=v({type:"geneVariant"},t.usecase).has("plot");if(r.mayGetMatchingGeneNames&&e&&await r.mayGetMatchingGeneNames(i,s,t),null!==(d=r.queries)&&void 0!==d&&d.defaultBlock2GeneMode&&e){const t=(0,l.getResult)(o,{input:s});if(Array.isArray(t.hits))for(let e=0;e<7&&t.hits[e];e++)a.push({name:t.hits[e],type:"geneVariant"})}}const h=await n.q.findTermByName(s,N,t.cohortStr,t.treeFilter,t.usecase,i);a.push(...h.map(A));a.forEach((t=>{"geneVariant"!=t.type&&(t.__ancestors=n.q.getAncestorIDs(t.id),t.__ancestorNames=n.q.getAncestorNames(t.id))})),e.send({lst:a})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message\|\|t})}}(s,n,C,T,S);if(s.getterminfo)return function(t,e,n){if(!t.tid)throw"no term id";e.send({terminfo:n.q.getTermInfo(t.tid)})}(s,n,C);if(s.phewas)return s.update?await d.update_image(s,n):s.getgroup?await d.getgroup(s,n):await d.trigger(s,n,T);if(s.gettermdbconfig)return u.make(s,n,T,S);if(s.getcohortsamplecount)return n.send({count:T.cohort.termdb.q.getcohortsamplecount(s.cohort)});if(s.getsamplecount)return n.send(await async function(t,e,n){const r=a().canDisplaySampleIds(t,n);if("list"==e.getsamplecount){return await f.get_samples(e.filter,n,r)}return await f.get_samplecount(e,n)}(e,s,T));if(s.getsamples)return await async function(t,e,n){const r=await f.get_samples(t.filter,n),o=r.map((t=>n.cohort.termdb.q.id2sampleName(t)));e.send({samples:o})}(s,n,T);if(s.getcuminc)return await async function(t,e,n){const r=await h.get_incidence(t,n);e.send(r)}(s,n,T);if(s.getsurvival)return await async function(t,e,n){const r=await p.get_survival(t,n);e.send(r)}(s,n,T);if(s.getregression)return await async function(t,e,n){const r=await m.get_regression(t,n);e.send(r)}(s,n,T);if(s.validateSnps)return n.send(await g.validate(s,C,T,S));if(s.getvariantfilter)return function(t,e){var n,r;if(e.track)return void t.send(e.track.variant_filter);t.send((null==e\|\|null===(n=e.queries)\|\|void 0===n\|\|null===(r=n.snvindel)\|\|void 0===r?void 0:r.variant_filter)\|\|{})}(n,T);if(s.getLDdata)return await async function(t,e,n){var r,o;if(!t.ldtkname)throw".ldtkname missing";if(null===(r=e.queries)\|\|void 0===r\|\|null===(o=r.ld)\|\|void 0===o\|\|!o.tracks)throw"no ld tk";const s=e.queries.ld.tracks.find((e=>e.name==t.ldtkname));if(!s)throw"unknown ld tk";if("object"!=typeof t.m)throw"q.m{} not object";if(!t.m.chr)throw"q.m.chr missing";if(!Number.isInteger(t.m.pos))throw"q.m.pos not integer";if(!t.m.ref\|\|!t.m.alt)throw"q.m{} invalid alleles";const a=t.m.ref+"."+t.m.alt,l=(s.nochr?t.m.chr.replace("chr",""):t.m.chr)+":"+t.m.pos+"-"+(t.m.pos+1),c=[];await(0,i.get_lines_bigfile)({args:[s.file,l],dir:s.dir,callback:e=>{const n=e.split("\t"),r=Number.parseInt(n[1]),o=Number.parseInt(n[2]),i=n[3],s=n[4],l=Number.parseFloat(n[5]);r==t.m.pos&&i==a?c.push({pos:o,alleles:s,r2:l}):o==t.m.pos&&s==a&&c.push({pos:r,alleles:i,r2:l})}}),n.send({lst:c})}(s,T,n);if(s.genesetByTermId)return function(t,e,n){if(!n.termMatch2geneSet)throw"this feature is not enabled";if("string"!=typeof t.genesetByTermId\|\|0==t.genesetByTermId.length)throw"invalid query term id";const r=n.q.getGenesetByTermId(t.genesetByTermId);e.send(r)}(s,n,C);if(s.getSampleScatter)return await b(e,s,n,T,S);if(s.getLowessCurve)return await _(e,s,n);if(s.getCohortsData)return await k(s,n,T);if(s.getViolinPlotData)return await w(s,n,T,S);if("mds3queryDetails"==s.for)return function(t,e){const n={},r=e.queries\|\|{};r.snvindel&&(n.snvindel={},r.snvindel.details&&(n.snvindel.details=r.snvindel.details),r.snvindel.populations&&(n.snvindel.populations=r.snvindel.populations));r.trackLst&&(n.trackLst=r.trackLst);if(r.ld){n.ld=JSON.parse(JSON.stringify(r.ld));for(const t of n.ld.tracks)delete t.file}t.send(n)}(n,T);if("termTypes"==s.for)return n.send(await T.getTermTypes(s));if("matrix"==s.for)return await async function(t,e,n,r,o){if(t.getPlotDataByName){if(!r.cohort.matrixplots)throw"ds.cohort.matrixplots missing for the dataset";if(!r.cohort.matrixplots.plots)throw"ds.cohort.matrixplots.plots missing for the dataset";const e=r.cohort.matrixplots.plots.find((e=>e.name===t.getPlotDataByName));if(!e)throw`plot name: q.getPlotDataByName=${getPlotDataByName} missing in ds.cohort.matrixplots.plots`;return void n.send(e.matrixConfig)}const i=await x(t,r,o);if(a().canDisplaySampleIds(e,r))for(const t of Object.values(i.samples))t.sampleName=r.sampleId2Name.get(t.sample);n.send(i)}(s,e,n,T,S);if("mds3variantData"==s.for)return await q(s,n,T,S);if(s.for,"convertSampleId"==s.for)return function(t,e,n){if(!n.convertSampleId)throw"not supported on this ds";if(!Array.isArray(t.inputs))throw"q.inputs[] not array";e.send({mapping:n.convertSampleId.get(t.inputs)})}(s,n,C);throw"termdb: doesn't know what to do"}catch(t){n.send({error:t.message\|\|t}),t.stack?console.log(t.stack):console.log(t)}}}function A(t){return JSON.parse(JSON.stringify(t))}function M(t,e){if("categorical"==t.type)return{};if("survival"==t.type)return{};if("integer"==t.type\|\|"float"==t.type)return t.bins.default;if("condition"==t.type)return{mode:e.mode,breaks:e.breaks,bar_by_grade:e.bar_by_grade,bar_by_children:e.bar_by_children,value_by_max_grade:e.value_by_max_grade,value_by_most_recent:e.value_by_most_recent,value_by_computable_grade:e.value_by_computable_grade};if("geneVariant"==t.type)return{};throw"unknown term type"}},2974:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getData:()=>f,getSampleData_dictionaryTerms_termdb:()=>d,mayInitiateMatrixplots:()=>h});const r=n(1017),{get_samples:o,get_term_cte:i,interpolateSqlValues:s}=n(2852),{getFilterCTEs:a}=n(5257),l=(n(9157),n(7147),n(7219),n(334)),c=n(3856),{getSampleData_snplstOrLocus:u}=(n(2852),n(8599));async function f(t,e,n){try{return function(t,e,n){if(!e.cohort)throw"cohort missing from ds";if(!t.terms)throw"missing 'terms' parameter";t.ds=e,t.genome=n;for(const e of t.terms)e.term.name\|\|(e.term=t.ds.cohort.termdb.q.termjsonByOneid(e.term.id)),e.q\|\|console.log("do something??");if(t.currentGeneNames&&!Array.isArray(t.currentGeneNames))throw"currentGeneNames[] is not array";t.filter0&&"string"==typeof t.filter0&&(t.filter0=JSON.parse(t.filter0))}(t,e,n),await async function(t){const[e,n]=function(t){const e=[],n=[];for(const r of t){const t=r.term.type;"snplst"==t\|\|"snplocus"==t\|\|"geneVariant"==t?n.push(r):e.push(r)}return[e,n]}(t.terms),{samples:r,refs:i}=await async function(t,e){var n,r,o,i;if(!e.length)return{samples:{},refs:{byTermId:{}}};if(null!==(n=t.ds)&&void 0!==n&&null!==(r=n.cohort)&&void 0!==r&&r.db)return await d(t,e);if(null!==(o=t.ds)&&void 0!==o&&null!==(i=o.variant2samples)&&void 0!==i&&i.get)return await async function(t,e){const n={filter0:t.filter0,filterObj:t.filter,genome:t.genome,get:"samples",twLst:e,useIntegerSampleId:!0};if(t.currentGeneNames){n.geneTwLst=[];for(const e of t.currentGeneNames)n.geneTwLst.push({term:{name:e,type:"geneVariant"}})}const r=await t.ds.variant2samples.get(n),o={},i={byTermId:{}};for(const t of r){const n={sample:t.sample_id};t.__sampleName&&(n.sampleName=t.__sampleName);for(const r of e){const e=t[r.term.id];Array.isArray(e)&&null!=e[0]&&null!=e[0]?n[r.term.id]={key:e[0],value:e[0]}:null!=e&&null!=e&&(n[r.term.id]={key:e,value:e})}o[t.sample_id]=n}return{samples:o,refs:i}}(t,e);throw"unknown method for dictionary terms"}(t,e);t.ds.getSampleIdMap&&(i.bySampleId=t.ds.getSampleIdMap(r));if(e.length&&!Object.keys(r).length)return{samples:r,refs:i};const s=await async function(t,e){if(!e.find((t=>"snplst"==t.term.type\|\|"snplocus"==t.term.type)))return;if(!t.filter)return;return new Set((await o(t.filter,t.ds)).map((t=>t.id)))}(t,n);for(const o of n)if("geneVariant"==o.term.type){const n=await t.ds.mayGetGeneVariantData(o,t);for(const[i,s]of n.entries()){var a,l;if(o.term.name in s)if(e.length\|\|i in r\|\|(r[i]={sample:i}),r[i])if(r[i][o.term.name]=s[o.term.name],null!==(a=t.ds.cohort)&&void 0!==a&&null!==(l=a.termdb)&&void 0!==l&&l.additionalSampleAttributes)for(const e of null===(c=t.ds.cohort)\|\|void 0===c\|\|null===(f=c.termdb)\|\|void 0===f?void 0:f.additionalSampleAttributes){var c,f;e in s&&(r[i][e]=s[e])}}}else{if("snplst"!=o.term.type&&"snplocus"!=o.term.type)throw"unknown type of non-dictionary term";{o.type=o.term.type;const t=new Map;await u(o,t,!0);for(const[e,n]of t){if(s&&!s.has(e))continue;e in r\|\|(r[e]={sample:e});const t={};for(const[e,r]of n.id2value)t[e]=r.value;r[e][o.term.id]=t}}}return{samples:r,refs:i}}(t)}catch(t){return t.stack&&console.log(t.stack),{error:t.message\|\|t}}}async function d(t,e){const n={},r={byTermId:{}},o={},s=await a(t.filter,t.ds),l=s?s.values.slice():[],c=await Promise.all(e.map((async(e,n)=>{const a=await i(t,l,n,s,e);if(a.bins&&(r.byTermId[e.term.id]={bins:a.bins}),a.events&&(r.byTermId[e.term.id]={events:a.events}),e.term.values){const t=Object.values(e.term.values);t.find((t=>"order"in t))&&(r.byTermId[e.term.id]={keyOrder:t.sort(((t,e)=>t.order-e.order)).map((t=>t.key))})}return"id"in e.term&&(o[e.term.id]=e),a}))).catch(console.error);l.push(...e.map((t=>t.term.id\|\|t.term.name)));const u=`WITH\n\t\t${s?s.filters+",":""}\n\t\t${c.map((t=>t.sql)).join(",\n")}\n\t\t${c.map((t=>`\n\t\t\tSELECT sample, key, value, ? as term_id\n\t\t\tFROM ${t.tablename}\n\t\t\t${s?`WHERE sample IN ${s.CTEname}`:""}\n\t\t\t`)).join("UNION ALL")}`,f=t.ds.cohort.db.connection.prepare(u).all(l),d=await async function(t){if(!t.currentGeneNames)return;const e=new Set;for(const n of t.currentGeneNames){const r={term:{name:n,type:"geneVariant"}},o=await t.ds.mayGetGeneVariantData(r,t);for(const[t,n]of o.entries())e.add(t)}return e}(t);for(const{sample:t,term_id:e,key:r,value:i}of f){if(d&&!d.has(t))continue;n[t]\|\|(n[t]={sample:t});o[e];n[t][e]={key:r,value:i}}return{samples:n,refs:r}}async function h(t){if(t.cohort.matrixplots){if(!Array.isArray(t.cohort.matrixplots.plots))throw"cohort.matrixplots.plots is not array";for(const e of t.cohort.matrixplots.plots){if(!e.name)throw".name missing 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h=d.has(i.genotype_types.het)?d.get(i.genotype_types.het).size:0,p=d.has(i.genotype_types.href)?d.get(i.genotype_types.href).size:0,m=d.has(i.genotype_types.halt)?d.get(i.genotype_types.halt).size:0,g=function(t,e,n,r,o,i){const s=[];let a;if(e.cohort.termdb.selectCohort&&t){const e=t.lst.find((t=>"cohortFilter"==t.tag));e&&(a=e.tvs.values.map((t=>t.key)).sort().join(","))}for(const t of e.cohort.termdb.q.getcategory2vcfsample()){if(a&&t.subcohort!=a)continue;const c=l.copy_term(e.cohort.termdb.q.termjsonByOneid(t.term_id));for(const e of t.categories){const[a,l,u]=_(n,e.group1lst);let f,d,h;e.group2lst?[f,d,h]=_(n,e.group2lst):(f=r-a,d=i-l,h=o-u),a+f+l+d+u+h!=0&&s.push({term:c,group_name:t.group_name,parent_name:t.parent_name,group1label:e.group1label,group2label:e.group2label,table:[u,h,a,f,l,d]})}}return s}(t.filter,n,c,h,p,m);r.testcount=g.length;{const t=[];for(let e=0;e<g.length;e++)t.push(e+"\t"+g[e].table.join("\t"));const e=await f(o.join(u.binpath,"utils/fisher.2x3.R"),t);let n=0;for(const t of e)g[n++].pvalue=Number(t.split("\t")[7])}r.maxlogp=function(t){let e=0;for(const n of t)0==n.pvalue?n.logp=100:n.logp=-Math.log10(n.pvalue),e=Math.max(e,n.logp);return e}(g);const y=function(t){const e=new Map;for(const n of t)e.has(n.group_name)\|\|e.set(n.group_name,[]),e.get(n.group_name).push(n);const n=[];for(const[t,r]of e)n.push({group_name:t,categories:r});return n}(g);r.tmpfile=await function(t){const e=[];for(const n of t)for(const t of n.categories)e.push(n.group_name+"\t"+t.logp+"\t"+t.pvalue+"\t"+JSON.stringify(t));return i.write_tmpfile(e.join("\n"))}(y),b(y,r,t);{const t=.05;r.hoverdots=g.filter((e=>e.pvalue<=t))}e.send(r)}async function h(t){if(!t.cohort)throw"ds.cohort missing";if(!t.cohort.termdb)throw"cohort.termdb missing";if(!t.cohort.termdb.phewas)throw"not allowed on this dataset";t.cohort.termdb.selectCohort?await async function(t){const e=await async function(t){if(!t.cohort.termdb.phewas.precompute_subcohort2totalsamples)return;for(const e in t.cohort.termdb.phewas.precompute_subcohort2totalsamples){const n=t.cohort.termdb.phewas.precompute_subcohort2totalsamples[e];if(n.termtype)for(const e in n.termtype)n.termtype[e].samples=await s.get_samples(n.termtype[e].filter,t)}return t.cohort.termdb.phewas.precompute_subcohort2totalsamples}(t),n=function(t){const e=new Map,n=t.cohort.db.connection.prepare("SELECT FROM subcohort_terms");for(const{term_id:t,cohort:r}of n.all())e.has(t)\|\|e.set(t,new Set),e.get(t).add(r);return e}(t),o=r.createWriteStream("category2vcfsample"),i=[];for(const{group_name:r,term:a}of t.cohort.termdb.q.getAlltermsbyorder()){if(!a.type)continue;if(!n.has(a.id)){i.push(a.id);continue}let l="";{const e=t.cohort.termdb.q.getTermParent(a.id);e&&(l=e.name)}const c=m(a,t,n);for(const n of c){const i=await s.get_rows(n);let c;if("categorical"==a.type\|\|"integer"==a.type\|\|"float"==a.type)c=g(i.lst,a,t);else{if("condition"!=a.type)throw"unknown term type";c=t.cohort.termdb.phewas.comparison_groups?y(i.lst,t):g(i.lst,a,t)}c=p({categories:c,q:n,subcohortTermtype2samples:e,term:a});for(const t of c)console.log(t.group1lst.length+(t.group2lst?"/"+t.group2lst.length:"")+"\t"+t.group1label+"\t"+a.name+"\t"+n.cohortname);o.write(n.cohortname+"\t"+r+"\t"+a.id+"\t"+l+"\t"+(n.term1_q?JSON.stringify(n.term1_q):"{}")+"\t"+JSON.stringify(c)+"\n")}}o.end((()=>{console.log('Phewas precompute result written to file "category2vcfsample".'),i.length&&(console.log(i.length+" empty terms:"),console.log(i.join("\n")))}))}(t):await async function(t){const[e]=await async function(t){let e=null;if(t.cohort.termdb.phewas.samplefilter4termtype&&t.cohort.termdb.phewas.samplefilter4termtype.condition){const n=await s.get_samples(t.cohort.termdb.phewas.samplefilter4termtype.condition.filter,t);if(t.track&&t.track.vcf&&t.track.vcf.sample2arrayidx){e=[];for(const r of n)t.track.vcf.sample2arrayidx.has(r)&&e.push(r)}else 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s){if(A(t,a,n),"snplst"!=t.type&&"snplocus"!=t.type)throw"unknown type of independent non-dictionary term";await M(t,a)}return[...a.values()]}(t,[t.outcome,...t.independent],e);y=(new Date).getTime(),v.NodeJS.getSampleData=(y-g)/1e3+" sec",g=(new Date).getTime();const r=function(t,e){const n={id:t.outcome.id,name:t.outcome.term.name,rtype:"numeric"};"logistic"==t.regressionType&&(n.categories={ref:t.outcome.refGrp,nonref:k(t.outcome)});"cox"==t.regressionType&&(n.timeToEvent={timeId:t.outcome.id+"_time",eventId:t.outcome.id+"_event",timeScale:t.outcome.q.timeScale},"age"==n.timeToEvent.timeScale&&(n.timeToEvent.agestartId=t.outcome.id+"_agestart",n.timeToEvent.ageendId=t.outcome.id+"_ageend"));const r=[];for(const e of t.independent)"snplst"==e.type\|\|"snplocus"==e.type?x(e,r,t):w(e,r,t);const o=[];for(const i of e){const{sample:e,id2value:s}=i;if(!s.has(t.outcome.id)){i.noOutcome=!0;continue}const a=s.get(t.outcome.id);let l=!1;for(const e of t.independent)if("snplocus"!=e.type)if("snplst"==e.type){for(const t of e.highAFsnps.keys())if(!s.get(t)){l=!0;break}}else{if(!s.get(e.id)){l=!0;break}}if(l)continue;const c={};if("linear"==t.regressionType&&(c[n.id]=a.value),"logistic"==t.regressionType&&(c[n.id]=a.key===t.outcome.refGrp?0:1),"cox"==t.regressionType){c[n.timeToEvent.eventId]=a.key;const{age_start:e,age_end:r}=a.value;c[n.timeToEvent.timeId]=r-e,"age"==t.outcome.q.timeScale&&(c[n.timeToEvent.agestartId]=e,c[n.timeToEvent.ageendId]=r)}for(const t of r){const e=s.get(t.id);c[t.id]=e?"numeric"===t.rtype?e.value:e.key:null}o.push(c)}const i={regressionType:t.regressionType,binpath:c.binpath,data:o,outcome:n,independent:r};return i}(t,n);y=(new Date).getTime(),v.NodeJS.makeRinput=(y-g)/1e3+" sec",function(t){const e=t.regressionType,n=t.outcome;if(t.data.length<m)throw"too few samples to fit model";let r=t.independent.length;if("cox"==e)if("time"==n.timeToEvent.timeScale)r+=2;else{if("age"!=n.timeToEvent.timeScale)throw"unknown cox regression time scale";r+=4}else r+=1;if(t.data.find((t=>Object.keys(t).length!=r)))throw"unequal number of variables in data entries";if("logistic"==e){if([...new Set(t.data.map((t=>t[n.id])))].find((t=>![0,1].includes(t))))throw"non-0/1 outcome values found"}if("cox"==e){if([...new Set(t.data.map((t=>t[n.timeToEvent.eventId])))].find((t=>![0,1].includes(t))))throw"non-0/1 outcome event values found"}for(const e of t.independent)if("numeric"==e.rtype){if(e.refGrp)throw`reference group given for '${e.id}'`}else{if("factor"!=e.rtype)throw`variable rtype='${e.rtype}' not recognized`;{if(!e.refGrp)throw`reference group not given for '${e.id}'`;if("snplst"==e.type\|\|"snplocus"==e.type)continue;const n=new Set(t.data.map((t=>t[e.id])));if(n.size<2)throw`fewer than 2 categories in data of variable='${e.id}'`;if(!n.has(e.refGrp))throw`reference group missing in data of variable='${e.id}'`}}}(r);const[s,a]=function(t){const e={},n={};if(e.outcome=t.outcome.id,n[t.outcome.id]="outcome",t.outcome.timeToEvent){const r=t.outcome.timeToEvent;e.outcome_time=r.timeId,n[r.timeId]="outcome_time",e.outcome_event=r.eventId,n[r.eventId]="outcome_event","age"==r.timeScale&&(e.outcome_agestart=r.agestartId,e.outcome_ageend=r.ageendId,n[r.agestartId]="outcome_agestart",n[r.ageendId]="outcome_ageend")}for(const[r,o]of t.independent.entries())e["id"+r+"_"]=o.id,n[o.id]="id"+r+"_";if(t.outcome.id=n[t.outcome.id],t.outcome.timeToEvent){const e=t.outcome.timeToEvent;e.timeId=n[e.timeId],e.eventId=n[e.eventId],"age"==e.timeScale&&(e.agestartId=n[e.agestartId],e.ageendId=n[e.ageendId])}for(const e of t.independent)if(e.id=n[e.id],e.interactions&&e.interactions.length>0)for(const[t,r]of e.interactions.entries())e.interactions[t]=n[r];for(const e of t.data)for(const t in e)e[n[t]]=e[t],delete e[t];return[e,n]}(r),l={resultLst:[]};return await Promise.all([q(r,s,t,l),N(t,n,r,l)]),console.log("benchmark:",v),l}catch(t){return t.stack&&console.log(t.stack),{error:t.message\|\|t}}}function _(t,e,n){if(!t.q.restrictAncestry)return;if(!("name"in t.q.restrictAncestry))throw".name missing from tw.q.restrictAncestry";if(!n.cohort.termdb.restrictAncestries)throw"ds.cohort.termdb.restrictAncestries missing";const r=n.cohort.termdb.restrictAncestries.find((e=>e.name==t.q.restrictAncestry.name));if(!r)throw"unknown ancestry for restriction: "+t.q.restrictAncestry.name;if(r.pcs)t.q.restrictAncestry.pcs=r.pcs;else{if(!r.PCfileBySubcohort)throw"unknown way of accessing pcs from ds.cohort.termdb.restrictAncestries: "+t.q.restrictAncestry.name;{if(!e.filter)throw"q.filter missing while trying to access subcohort for PCfileBySubcohort";const n=C(e.filter,"cohortFilter");if(!n)throw"tvs by tag=cohortFilter missing from q.filter.lst[] while trying to access subcohort for PCfileBySubcohort";const o=n.tvs.values.map((t=>t.key)).sort().join(","),i=r.PCfileBySubcohort[o];if(!i)throw"unknown key for PCfileBySubcohort: "+o;if(!i.pcs)throw"pcs Map() missing from PCfileBySubcohort[]: "+o;t.q.restrictAncestry.pcs=i.pcs}}}function w(t,e,n){const o={id:t.id,name:t.term.name,type:"spline"==t.q.mode?"spline":"other",rtype:"continuous"==t.q.mode\|\|"spline"==t.q.mode?"numeric":"factor"};if(t.interactions.length>0){o.interactions=[];for(const e of t.interactions){const t=n.independent.find((t=>t.id==e));if("snplst"==t.type)for(const e of t.highAFsnps.keys())o.interactions.push(e);else{if("snplocus"==t.type)continue;o.interactions.push(e)}}}"factor"===o.rtype&&(o.refGrp=t.refGrp),"spline"==t.q.mode&&(o.spline={knots:t.q.knots.map((t=>Number(t.value)))},n.independent.find((t=>"snplocus"==t.type))\|\|(o.spline.plotfile=r.join(c.cachedir,Math.random().toString()+".png"))),e.push(o)}function x(t,e,n){for(const r of t.highAFsnps.keys()){const o={id:r,name:r,type:t.type};3==t.q.geneticModel?(o.rtype="factor",o.refGrp=t.q.snp2refGrp[r]):o.rtype="numeric";for(const e of n.independent)e.interactions.includes(t.id)&&(o.interactions\|\|(o.interactions=[]),o.interactions.push(e.id));e.push(o)}if(t.q.restrictAncestry)for(const n of t.q.restrictAncestry.pcs.keys())e.push({id:n,name:n,type:"float",rtype:"numeric"})}function k(t){if("condition"==t.term.type){for(const e of t.q.groups)if(e.name!=t.refGrp)return e;throw"nonref group not found for logistic outcome"}if("predefined-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!Number.isInteger(t.q.groupsetting.predefined_groupset_idx))throw'outcome.q.predefined_groupset_idx not integer when q.type is "predefined-groupset"';if(!t.term.groupsetting)throw"outcome.term.groupsetting missing";const e=t.term.groupsetting.lst[t.q.groupsetting.predefined_groupset_idx];if(!e)throw"groupset not found by 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e={},[r,o]=t.shift().split(":");e.term1=n[r],e.term2=n[o],e.lst=t,i.data.type3.interactions.push(e)}else{const e=n[t.shift()];i.data.type3.terms[e]\|\|(i.data.type3.terms[e]=t)}if(i.data.type3.label="Type III statistics",s.totalSnpEffect){if(1!=s.totalSnpEffect.rows.length)throw"total SNP effect table should have 1 row";i.data.totalSnpEffect={header:s.totalSnpEffect.header.slice(0,4)};const t=s.totalSnpEffect.rows[0].slice(0,4),e=s.totalSnpEffect.rows[0][4].split(";"),r=e.findIndex((t=>!t.includes(":"))),o=e.splice(r,1)[0];i.data.totalSnpEffect.snp=n[o];const a=[];for(const t of e){if(!t.includes(":"))throw"expected interaction";const[e,r]=t.split(":");a.push({term1:n[e],term2:n[r]})}i.data.totalSnpEffect.interactions=a,i.data.totalSnpEffect.lst=t,i.data.totalSnpEffect.label="Total SNP effect"}s.tests&&(i.data.tests=s.tests,i.data.tests.label="Statistical tests"),i.data.other=s.other,i.data.other.label="Other summary statistics";for(const e of 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i={time:e.outcome_time,event:e.outcome_event},l=s.samples.get(r);if(!l)continue;const[c,u]=l.split("/");i.series=s.effAle==c\|\|s.effAle==u?"1":"2",t.push(i)}new Set(t.map((t=>t.series))).size<2?i.add(r):o.data[r]=t}const s=await d(o);let a;for(const[e,n]of t.lowAFsnps){if(i.has(e)){a={pvalue:"NA",msg:"Cannot perform cumulative incidence test on this snp - at least one allele is not found in any sample"}}else{var l;if(1==!(null!==(l=s[e].tests)&&void 0!==l&&l.length))throw"must have a single test";const t=Number(s[e].tests[0].pvalue);if(!Number.isFinite(t))throw"invalid pvalue";a={pvalue:Number(t.toFixed(4)),ci_data:{[e]:s[e]}}}const n={id:e,AFstr:t.snpid2AFstr.get(e),data:{headerRow:S(e,t),cuminc:a}};r.resultLst.push(n)}}(i,e,n,o)}y=(new Date).getTime(),v.NodeJS.snplocusPostprocess=(y-g)/1e3+" sec"}}function S(t,e){const n=e.snpgt2count.get(t);if(!n)return{k:"Error",v:"Variant not found"};if(e.monomorphicLst.includes(t)){const[t,e]=[...n][0];return{k:"Genotype",v:t+"="+e}}const r=[`${0==e.q.alleleType?"Minor":"Alternative"} allele=${e.highAFsnps.has(t)?e.highAFsnps.get(t).effAle:e.lowAFsnps.get(t).effAle}`,"AF="+e.snpid2AFstr.get(t)];for(const[t,e]of n)r.push(t+"="+e);return{k:"Variant:",v:r.join("   ")}}function A(t,e,n){if(t.q.restrictAncestry)for(const[n,r]of t.q.restrictAncestry.pcs)for(const[t,o]of r)e.has(t)&&e.get(t).id2value.set(n,{key:o,value:o})}async function M(t,e,n){const o=(await u.read_file(r.join(c.cache_snpgt.dir,t.q.cacheid))).split("\n"),i=o[0].split("\t").slice(c.cache_snpgt.sampleColumn).map(Number);if(n)for(const t of i)e.set(t,{id2value:new Map});const s=i.map((t=>e.has(t))),a=new Map;for(let e=1;e<o.length;e++){const n=o[e].split("\t"),r=n[0],l={refAle:n[3],altAles:n[4].split(","),samples:new Map};t.q.snp2effAle?l.effAle=t.q.snp2effAle[r]:l.effAle=l.altAles[0],a.set(r,l);for(const[t,e]of i.entries()){if(!s[t])continue;const 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o;if(null!==(v=r.colorTW.term.values)&&void 0!==v&&v[i])o=null===(b=r.colorTW.term.values)\|\|void 0===b?void 0:b[i];else for(const t in r.colorTW.term.values){var A,M;(null===(A=r.colorTW.term.values)\|\|void 0===A?void 0:A[t].label)==i&&(o=null===(M=r.colorTW.term.values)\|\|void 0===M?void 0:M[t])}if(o&&"color"in o)s.color=o.color;else if(null!==(k=n.refs)&&void 0!==k&&null!==(S=k.byTermId[r.colorTW.term.id])&&void 0!==S&&S.bins){const o=n.refs.byTermId[r.colorTW.term.id].bins.find((t=>t.name===i));o?s.color=o.color:(s.color=e[t],t--)}else"geneVariant"!=r.colorTW.term.type&&(s.color=h(i))}}let o=1;for(const[t,e]of Object.entries(s.shapeMap))"shape"in e\|\|(e.shape=o),o++;s.colorLegend=r.colorTW?q(s.colorMap,r.colorTW,n.refs):[["Default",{sampleCount:e.length,color:"blue"}]],s.colorLegend.push(["Ref",{sampleCount:t.length,color:null!==(p=r.colorTW)&&void 0!==p&&null!==(m=p.term.values)&&void 0!==m&&m.Ref?null===(g=r.colorTW.term.values)\|\|void 0===g?void 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t)}e[o]=x(!0,t,n)\|\|x(!1,t,n),e[o]\|\|(e[o]=k(s[0])),e.hidden[o]=!!n.q.hiddenValues&&e[o]in n.q.hiddenValues}}(t,e,n,r,o);else{var s,a,l,u,f,d;if(i=null==t\|\|null===(s=t[n.id\|\|n.term.name])\|\|void 0===s?void 0:s.key,null!==(a=n.term.values)&&void 0!==a&&null!==(l=a[i])&&void 0!==l&&l.label)i=null===(f=n.term.values)\|\|void 0===f\|\|null===(d=f[i])\|\|void 0===d?void 0:d.label,e.hidden[o]=!!n.q.hiddenValues&&i in n.q.hiddenValues;else e.hidden[o]=!!n.q.hiddenValues&&(null==t\|\|null===(u=t[n.id])\|\|void 0===u?void 0:u.key)in n.q.hiddenValues;i&&(e[o]=i.toString(),null==r[i]?r[i]={sampleCount:1}:r[i].sampleCount++)}}function x(t,e,n){var r;const o=null==e\|\|null===(r=e[n.term.name])\|\|void 0===r?void 0:r.values;for(const[e,r]of Object.entries(c.dt2label)){const r=o.find((t=>{const r=k(t),o=!(n.q.hiddenValues&&r in n.q.hiddenValues);return t.dt==e&&o}));if(!r)continue;const i="WT"==r.class\|\|"Blank"==r.class;if(t&&i)continue;return k(r)}}function k(t){var e;const n=t.dt,r=c.mclass[t.class],o=null===(e=c.morigin[t.origin])\|\|void 0===e?void 0:e.label,i=o?`${o[0]} ${c.dt2label[n]}`:c.dt2label[n];return`${r.label},${i}`}function q(t,e,n){var r;let o=[];if(!e\|\|0==t.size)return o;if("geneVariant"==e.term.type)o=Object.entries(t),o.sort(((t,e)=>t[0]<e[0]?-1:t[0]>e[0]?1:0));else if(null!=n&&null!==(r=n.byTermId[e.term.id])&&void 0!==r&&r.bins){const r=n.byTermId[e.term.id].bins;for(const e of r)t[e.name]&&o.push([e.name,t[e.name]]);for(const[e,n]of Object.entries(t))o.some((t=>t[0]===e))\|\|o.push([e,n])}else o=Object.entries(t),o.sort(((t,n)=>{let r,o;for(const i in e.term.values){const s=e.term.values[i];(s.label&&t[0]==s.label\|\|i==t[0])&&(r=s),(s.label&&n[0]==s.label\|\|i==n[0])&&(o=s)}var i,s;return r&&"order"in r?(null===(i=r)\|\|void 0===i?void 0:i.order)<(null===(s=o)\|\|void 0===s?void 0:s.order)?-1:1:t[1].sampleCount>n[1].sampleCount?-1:1}));return o}function N(t,e){var n,r;return!(null!==(n=t.values)&&void 0!==n&&null!==(r=n[e])&&void 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missing";if(!r.has("ancestry"))throw"ancestry table missing";if(t.cohort.termdb.selectCohort&&!r.has("subcohort_terms"))throw"subcohort_terms table is missing while termdb.selectCohort is enabled";t.cohort.termdb.q={};const a=t.cohort.termdb.q;if(r.has("buildDate")&&(a.get_buildDate=n.prepare("select date from buildDate")),r.has("term2genes")){t.cohort.termdb.termMatch2geneSet=!0;const e=n.prepare("SELECT genes FROM term2genes WHERE id=?"),r=new Map;a.getGenesetByTermId=t=>{if(r.has(t))return r.get(t);const n=e.get(t);if(n&&n.genes){const e=JSON.parse(n.genes);return r.set(t,e),e}}}if(r.has("sampleidmap")){const e=new Map,r=new Map,o=n.prepare("SELECT FROM sampleidmap");let i=0;for(const{id:t,name:n}of o.all())e.set(t,n),r.set(n,t),i++;if(a.id2sampleName=t=>e.get(t),a.sampleName2id=t=>r.get(t),t.cohort.termdb.selectCohort){const t=n.prepare("SELECT cohort,sample_count from cohorts").all(),e={};for(const n of t)e[n.cohort]=n.sample_count;a.getcohortsamplecount=t=>t?e[t]\|\|0:i}else a.getcohortsamplecount=()=>i}if(r.has("category2vcfsample")){const t=n.prepare("SELECT * FROM category2vcfsample");let e;a.getcategory2vcfsample=()=>{if(e)return e;e=t.all();for(const t of e)t.q=JSON.parse(t.q),t.categories=JSON.parse(t.categories);return e}}if(r.has("alltermsbyorder")){const t=n.prepare("SELECT * FROM alltermsbyorder");let e;a.getAlltermsbyorder=()=>{if(e)return e;const n=t.all();e=[];for(const t of n){const n=a.termjsonByOneid(t.id);n&&e.push({group_name:t.group_name,term:n})}return e}}{const t=n.prepare("SELECT name, jsondata FROM terms WHERE id=?"),e=new Map;a.termjsonByOneid=n=>{if(e.has(n))return e.get(n);const r=t.get(n);if(r){const t=JSON.parse(r.jsondata);return t.id=n,t.name=r.name\|\|t.name,e.set(n,t),t}}}{const t=n.prepare("select id from terms where parent_id=?"),e=new Map;a.termIsLeaf=n=>{if(e.has(n))return e.get(n);let r=!0;const o=t.get(n);return o&&o.id&&(r=!1),e.set(n,r),r}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types, s.child_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE parent_id is null\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),e=new Map;a.getRootTerms=(n="")=>{const r=n;if(e.has(r))return e.get(r);const o=t.all(n).map((t=>{const e=JSON.parse(t.jsondata);return e.id=t.id,e.name=t.name\|\|e.name,e.included_types=t.included_types?t.included_types.split(","):["TO-DO-PLACEHOLDER"],e.child_types=t.child_types?t.child_types.split(","):[],e}));return e.set(r,o),o}}{const t=n.prepare("SELECT parent_id FROM terms WHERE id=?");{const e=new Map;a.termHasParent=n=>{if(e.has(n))return e.get(n);let r=!1;const o=t.get(n);return o&&o.parent_id&&(r=!0),e.set(n,r),r}}{const e=new Map;a.getTermParentId=n=>{if(e.has(n))return e.get(n);let r;const o=t.get(n);return o&&o.parent_id&&(r=o.parent_id),e.set(n,r),r}}{const t=new Map;a.getTermParent=e=>{if(t.has(e))return t.get(e);const n=a.getTermParentId(e);let r;return n&&(r=a.termjsonByOneid(n)),t.set(e,r),r}}}{const t=n.prepare("SELECT id, name, type, jsondata, s.included_types, s.child_types \n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=? \n\t\t\tWHERE id IN (SELECT id FROM terms WHERE parent_id=?)\n\t\t\tGROUP BY id\n\t\t\tORDER BY child_order ASC"),e=new Map;a.getTermChildren=(n,r="")=>{const o=n+";;"+r;if(e.has(o))return e.get(o);const i=t.all([r,n]);let s;return i&&(s=i.map((t=>{const e=JSON.parse(t.jsondata);return e.id=t.id,e.name=t.name\|\|e.name,e.included_types=t.included_types?t.included_types.split(","):[],e.child_types=t.child_types?t.child_types.split(","):[],e}))),e.set(o,s),s}}{const t=n.prepare("SELECT id, name, jsondata, s.included_types\n\t\t\tFROM terms t\n\t\t\tJOIN subcohort_terms s ON s.term_id = t.id AND s.cohort=?\n\t\t\tWHERE name LIKE ?");a.findTermByName=(e,n=10,r="",o=null,i=null,a=null)=>{const l=t.all([r,"%"+e+"%"]);if(l){const t=a\|\|{equals:[],startsWith:[],startsWord:[],includes:[]};for(const n of l){if(!n.jsondata)continue;const r=n.name.toLowerCase(),o=JSON.parse(n.jsondata);o.id=n.id,o.name=n.name\|\|o.name,o.included_types=n.included_types?n.included_types.split(","):[],i&&!(0,s.CG)(o,i).has("plot")\|\|(r===e?t.equals.push(o):r.startsWith(e)?t.startsWith.push(o):r.includes(" "+e)?t.startsWord.push(o):t.includes.push(o))}return[...t.equals,...t.startsWith,...t.startsWord,...t.includes].slice(0,n)}}}{const t=n.prepare("SELECT MAX(value) AS v FROM anno_integer WHERE term_id=?"),e=n.prepare("SELECT MAX(value) AS v FROM anno_float WHERE term_id=?"),r=new Map;a.findTermMaxvalue=(n,o)=>{if(r.has(n))return r.get(n);const i=(o?t:e).get(n);return i?(r.set(n,i.v),i.v):void 0}}{const t=n.prepare("SELECT ancestor_id FROM ancestry WHERE term_id=?"),e=new Map;a.getAncestorIDs=n=>{if(e.has(n))return e.get(n);const r=t.all(n).map((t=>t.ancestor_id));return e.set(n,r),r}}{const t=n.prepare("SELECT t.name FROM ancestry 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l=n.queries.snvindel.byrange._tk;if(t.filter){const e=new Set((await s.get_samples(t.filter,n)).map((t=>t.id)));if(0==e.size)throw"no samples from filter";c=l.samples.map((t=>e.has(t.name)))}else c=l.samples.map((t=>!0));const u=(await i.read_file(o.join(a.cache_snpgt.dir,t.cacheid))).split("\n"),f=new Set,d=[];for(let t=1;t<u.length;t++){const e=u[t].split("\t"),n=e[0],r=e[3],o={},i={};for(let t=a.cache_snpgt.sampleColumn;t<e.length;t++){const n=e[t];if(!n)continue;if(!c[t-a.cache_snpgt.sampleColumn])continue;f.add(l.samples[t-a.cache_snpgt.sampleColumn].name),i[n]=1+(i[n]\|\|0);const r=n.split("/");for(const t of r)o[t]=1+(o[t]\|\|0)}const s=[];for(const t in o)s.push({allele:t,count:o[t],isRef:t==r});d.push({snpid:n,alleles:s,gt2count:i})}return{numOfSampleWithAnyValidGT:f.size,snps:d}}(t,0,n);if(t.snptext)return await async function(t,e,n){if(!n.snp)throw"snp not supported by genome";if(!t.snptext)throw".snptext missing";const s=function(t){const e=[];for(const n of t.trim().split("\n")){const[t,r]=n.trim().split(/[\s\t]/);if(t&&t.startsWith("rs")){if(e.find((e=>e.rsid==t)))continue;const n={rsid:t,snpid:t};r&&(n.effectAllele=r),e.push(n)}else e.push({rsid:t,snpid:t,invalid:"INVALID RSID"})}return e}(t.snptext);if(!s.length)throw"no snps";await async function(t,e){for(const n of t)if(!n.invalid)if(n.chr&&"string"==typeof n.chr){const t=e.chrlookup[n.chr.toUpperCase()];if(!t){n.invalid=!0;continue}if(!Number.isInteger(n.pos)){n.invalid=!0;continue}if(n.pos<=0\|\|n.pos>=t.len){n.invalid=!0;continue}}else if(n.rsid){const t=await i.query_bigbed_by_name(e.snp.bigbedfile,n.rsid),r=[];for(const n of t){const t=n.split("\t"),o=e.chrlookup[t[0].toUpperCase()];o&&o.major&&r.push(t)}if(0==r.length){n.invalid=!0;continue}const o=r[0];n.chr=o[0],n.pos=Number.parseInt(o[1]),n.dbsnpRef=o[4],n.dbsnpAlts=o[6].split(",").filter(Boolean)}else n.invalid=!0;if(!t.find((t=>!t.invalid)))throw"no valid variants"}(s,n);const l=await async function(t,e,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 l=new Set,u=[];for(const t of e){if(t.invalid)continue;let e;var d;if(s.chr2files){if(e=null===(d=s.chr2files)\|\|void 0===d?void 0:d[t.chr].file,!e)throw"chr not in chr2files"}else if(s.chr2bcffile){if(e=s.chr2bcffile[t.chr],!e)throw"chr not in chr2bcffile"}else e=s.file\|\|s.url;l.add(e);const n=(s.nochr?t.chr.replace("chr",""):t.chr)+"\t"+(t.pos+1);u.push(n)}const h=o.join(a.cachedir,await i.write_tmpfile(u.join("\n"))),p=o.join(a.cachedir,await i.write_tmpfile([...l].join("\n")));await i.get_lines_bigfile({isbcf:!0,args:["query","-R",h,"-f",c,"-v",p],dir:s.dir,callback:t=>{const n=t.split("\t"),r=(s.nochr?"chr":"")+n[0],o=n[1],i=n[2],a=n[3].split(","),l=e.find((t=>{if(t.chr==r&&t.pos===o-1&&t.dbsnpRef==i&&t.dbsnpAlts.some((t=>a.includes(t))))return t}));if(l){l.referenceAllele=i,l.altAlleles=a,l.gtlst=[];for(let t=4;t<n.length;t++)l.gtlst.push(n[t]==f?"":n[t])}}}),r.unlink(h,(()=>{})),r.unlink(p,(()=>{}));const m=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid\|\|t.gtlst&&(m.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele\|\|"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const g=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4Math.random());return await i.write_file(o.join(a.cache_snpgt.dir,g),m.join("\n")),g}(t,s,e);return{snps:s,cacheid:l}}(t,n,h);if(t.chr)return await async function(t,e,n){const r=Number(t.start),s=Number(t.stop);if(!Number.isInteger(r)\|\|!Number.isInteger(s))throw"start/stop are not integers";if(r>s\|\|r<0)throw"invalid start/stop coordinate";let c,h;if(e.track){if(c=e.track.vcf,!c)throw"ds.track.vcf missing";if(h=c.chr2bcffile[t.chr],!h)throw"chr not in chr2bcffile"}else{var m;if(c=e.queries.snvindel.byrange._tk,c.chr2files)h=null===(m=c.chr2files)\|\|void 0===m?void 0:m[t.chr].file;else h=c.file\|\|c.url;if(!h)throw"no bcf file"}const g=(c.nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+s,y=["query",h,"-r",g,"-f",u];t.variant_filter&&p(t.variant_filter,y);const v={snps:[]},b=["snpid\tchr\tpos\tref\talt\teff\t"+c.samples.map((t=>t.name)).join("\t")];return await i.get_lines_bigfile({isbcf:!0,args:y,dir:c.dir,callback:(e,n)=>{if(v.snps.length>=d)return n.kill(),void(v.reachedVariantLimit=!0);const r=e.split("\t"),o=Number(r[0])-1,i=r[2],s=r[3].split(","),a=o+"."+i+"."+s.join(","),u={snpid:a,chr:t.chr,pos:o};l(c,i,s,u,r[4],r[1]);for(const t of u.mlst)t.vcf_id&&(t.mname=t.vcf_id);v.snps.push(u);const h=[a,t.chr,o,i,s.join(","),""];for(let t=5;t<r.length;t++)h.push(r[t]==f?"":r[t]);b.push(h.join("\t"))}}),v.cacheid=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4Math.random()),await i.write_file(o.join(a.cache_snpgt.dir,v.cacheid),b.join("\n")),v}(t,n);throw"unknown how to validate"}catch(t){return t.stack&&console.log(t.stack),{error:t.message\|\|t}}}function p(t,e){const n=[];for(const e of t.lst)if(e.tvs.values){const t=e.tvs.isnot?"!=":"=";for(const r of e.tvs.values){const o=isNaN(r.key)?`"${r.key}"`:Number(r.key);n.push(`INFO/${e.tvs.term.id}${t}${o}`)}}else{if(!e.tvs.ranges)throw`unknown tvs spec for info_field: type=${e.type}, term.id=${e.tvs.term.id}`;for(const t of e.tvs.ranges)"start"in t&&n.push(`INFO/${e.tvs.term.id} ${t.startinclusive?">=":">"} ${t.start}`),"stop"in t&&n.push(`INFO/${e.tvs.term.id} ${t.stopinclusive?"<=":"<"} ${t.stop}`)}0!=n.length&&e.push("-i",n.join(" && "))}},2747:(t,e,n)=>{"use strict";n.r(e),n.d(e,{groupset:()=>s,values:()=>o});var r=n(2852);const o={getCTE(t,e,n,o,i){i.push(e.id);const s=(0,r.getUncomputableClause)(e,o);return i.push(...s.values),{sql:`${t} AS (\n\t\t\t\tSELECT sample,value as key, value as value\n\t\t\t\tFROM 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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 ${i}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${s.join("\nUNION ALL\n")}\n\t\t)`,tablename:t}}},2852:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getUncomputableClause:()=>v,get_bins:()=>_,get_numericMinMaxPct:()=>x,get_numericsummary:()=>w,get_rows:()=>p,get_rows_by_one_key:()=>h,get_samplecount:()=>f,get_samples:()=>u,get_summary:()=>g,get_summary_numericcategories:()=>d,get_term_cte:()=>m,interpolateSqlValues:()=>k});const r=n(9699),o=n(4048),i=n(5257).getFilterCTEs,s=n(827),a=n(2747),l=n(9723),c=n(610).s;n(334);async function u(t,e,n=!1){const r=await i(t,e),o=e.cohort.db.connection.prepare(r?`WITH ${r.filters} SELECT sample as id, name FROM ${r.CTEname} join sampleidmap on sample = sampleidmap.id`:"SELECT id, name FROM sampleidmap");let s;if(s=r?o.all(r.values):o.all(),n)return s;for(const t of s)delete t.name;return s}async function f(t,e){if(!t.filter)throw"filter missing";let n;if("object"==typeof t.filter)n=t.filter;else{if("string"!=typeof t.filter)throw"q.filter not obj or str";n=JSON.parse(t.filter)}const r=await i(n,e),o=`WITH ${r.filters}\n\t\tSELECT 'FILTERED_COHORT' as subcohort, count(distinct sample) as samplecount \n\t\tFROM ${r.CTEname}`;return e.cohort.db.connection.prepare(o).all(r.values)}async function d(t){const e=t.ds.cohort.termdb.q.termjsonByOneid(t.term_id);if("integer"!=e.type&&"float"!=e.type)throw"term is not numeric";if(!e.values)return[];const n=await i(t.filter,t.ds),r=n?n.values.slice():[];r.push(t.term_id);const o=[];for(const t in e.values)o.push("?"),r.push(Number(t));const s=`\n\t\t${n?"WITH "+n.filters:""}\n\t\tSELECT count(sample) AS samplecount,value\n\t\tFROM anno_${e.type}\n\t\tWHERE term_id=?\n\t\t${n?"AND sample IN "+n.CTEname:""}\n\t\tAND value IN (${o.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(s).all(r)}async function h(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await i(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const o=`\n\t\t${e?"WITH "+e.filters:""}\n\t\tSELECT sample, value\n\t\tFROM anno_${r.type}\n\t\tWHERE term_id=?\n\t\t${e?" AND sample IN "+e.CTEname:""}`;return t.ds.cohort.db.connection.prepare(o).all(n)}async function p(t,e={}){"string"==typeof t.filter&&(t.filter=JSON.parse(decodeURIComponent(t.filter)));const n=Object.assign({withCTEs:!0,columnas:"t1.sample AS sample",groupby:""},e),r=await i(t.filter,t.ds),o=r?r.values.slice():[],s=await m(t,o,0,r),a=await m(t,o,1,r),l=await m(t,o,2,r),c=[s,a,l].map(((t,e)=>`\n\t\tSELECT sample, key, value, ${e} as termNum\n\t\tFROM ${t.tablename}\n\t\t${r?"WHERE sample IN "+r.CTEname:""}\n\t`)).join("\nUNION ALL\n"),u=`WITH\n\t\t${r?r.filters+",":""}\n\t\t${s.sql},\n\t\t${a.sql},\n\t\t${l.sql}\n\t\t${c}`;try{const e=t.ds.cohort.db.connection.prepare(u).all(o),i=new Map;for(const t of e){i.has(t.sample)\|\|i.set(t.sample,{sample:t.sample});const e=i.get(t.sample),n=`key${t.termNum}`;n in e\|\|(e[n]=[]),e[n].push(t)}const c=[],f=new Map;for(const e of i.values())if("key1"in e){if(t.term0_q&&t.term0_id){if(!("key0"in e))continue}else e.key0=[{key:"",value:""}];if(t.term2_q&&(t.term2_id\|\|"samplelst"===t.term2.type)){if(!("key2"in e))continue}else e.key2=[{key:"",value:""}];e.rows=[];for(const t of e.key0)for(const n of e.key1)for(const r of e.key2)e.rows.push({sample:e.sample,key0:t.key,val0:t.value,key1:n.key,val1:n.value,key2:r.key,val2:r.value});for(const t of e.rows)if(n.groupby){if(!f.has(t[n.groupby])){const e=Object.assign({samplecount:0},t);c.push(e),f.set(t[n.groupby],e)}f.get(t[n.groupby]).samplecount++}else c.push(t)}return n.withCTEs?{lst:c,CTE0:s,CTE1:a,CTE2:l,filter:r}:c}catch(t){throw console.log("error in sql:\n",k(u,o)),t}}async function m(t,e,n,r,o=null){const i=o&&o.term\|\|t[`term${n}`],u=i?i.id:t["term"+n+"_id"];if("samplelst"!=(null==i?void 0:i.type))if(o\|\|1!=n){if(!u){const t="samplekey_"+n;return{tablename:t,sql:`${t} AS (\nSELECT null AS sample, '' as key, '' as value\n)`}}}else if(!u)throw"missing term1 id";const f=i&&i.type?i:t.ds.cohort.termdb.q.termjsonByOneid(u);if(!f)throw`no term 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Fr(){var t=Rr,e=Ir,n=Pr,r=960,o=500,i=20,s=2,a=3i,l=r+2a>>s,c=o+2a>>s,u=Nr(20);function f(r){var o=new Float32Array(lc),u=Math.pow(2,-s),f=-1;for(const i of r){var d=(t(i,++f,r)+a)u,h=(e(i,f,r)+a)u,p=+n(i,f,r);if(d>=0&&d<l&&h>=0&&h<c){var m=Math.floor(d),g=Math.floor(h),y=d-m-.5,v=h-g-.5;o[m+gl]+=(1-y)(1-v)p,o[m+1+gl]+=y(1-v)p,o[m+1+(g+1)l]+=yvp,o[m+(g+1)l]+=(1-y)vp}}return(0,Or.u8)({data:o,width:l,height:c},iu),o}function d(t){var e=f(t),n=u(e),r=Math.pow(2,2s);return Array.isArray(n)\|\|(n=(0,xr.ZP)(Number.MIN_VALUE,(0,Er.Z)(e)/r,n)),jr().size([l,c]).thresholds(n.map((t=>tr)))(e).map(((t,e)=>(t.value=+n[e],h(t))))}function h(t){return t.coordinates.forEach(p),t}function p(t){t.forEach(m)}function m(t){t.forEach(g)}function g(t){t[0]=t[0]Math.pow(2,s)-a,t[1]=t[1]Math.pow(2,s)-a}function y(){return l=r+2(a=3i)>>s,c=o+2a>>s,d}return d.contours=function(t){var e=f(t),n=jr().size([l,c]),r=Math.pow(2,2s),o=t=>{t=+t;var o=h(n.contour(e,tr));return o.value=t,o};return Object.defineProperty(o,"max",{get:()=>(0,Er.Z)(e)/r}),o},d.x=function(e){return arguments.length?(t="function"==typeof e?e:Nr(+e),d):t},d.y=function(t){return arguments.length?(e="function"==typeof t?t:Nr(+t),d):e},d.weight=function(t){return arguments.length?(n="function"==typeof t?t:Nr(+t),d):n},d.size=function(t){if(!arguments.length)return[r,o];var e=+t[0],n=+t[1];if(!(e>=0&&n>=0))throw new Error("invalid size");return r=e,o=n,y()},d.cellSize=function(t){if(!arguments.length)return 1<<s;if(!((t=+t)>=1))throw new Error("invalid cell size");return s=Math.floor(Math.log(t)/Math.LN2),y()},d.thresholds=function(t){return arguments.length?(u="function"==typeof t?t:Array.isArray(t)?Nr(kr.call(t)):Nr(t),d):u},d.bandwidth=function(t){if(!arguments.length)return Math.sqrt(i(i+1));if(!((t=+t)>=0))throw new Error("invalid bandwidth");return i=(Math.sqrt(4tt+1)-1)/2,y()},d}const Lr=134217729,Dr=33306690738754706e-32;function zr(t,e,n,r,o){let i,s,a,l,c=e[0],u=r[0],f=0,d=0;u>c==u>-c?(i=c,c=e[++f]):(i=u,u=r[++d]);let h=0;if(f<t&&d<n)for(u>c==u>-c?(s=c+i,a=i-(s-c),c=e[++f]):(s=u+i,a=i-(s-u),u=r[++d]),i=s,0!==a&&(o[h++]=a);f<t&&d<n;)u>c==u>-c?(s=i+c,l=s-i,a=i-(s-l)+(c-l),c=e[++f]):(s=i+u,l=s-i,a=i-(s-l)+(u-l),u=r[++d]),i=s,0!==a&&(o[h++]=a);for(;f<t;)s=i+c,l=s-i,a=i-(s-l)+(c-l),c=e[++f],i=s,0!==a&&(o[h++]=a);for(;d<n;)s=i+u,l=s-i,a=i-(s-l)+(u-l),u=r[++d],i=s,0!==a&&(o[h++]=a);return 0===i&&0!==h\|\|(o[h++]=i),h}function Br(t){return new Float64Array(t)}const $r=22204460492503146e-32,Zr=11093356479670487e-47,Gr=Br(4),Ur=Br(8),Wr=Br(12),Jr=Br(16),Hr=Br(4);function Vr(t,e,n,r,o,i){const s=(e-i)(n-o),a=(t-o)(r-i),l=s-a;if(0===s\|\|0===a\|\|s>0!=a>0)return l;const c=Math.abs(s+a);return Math.abs(l)>=33306690738754716e-32c?l:-function(t,e,n,r,o,i,s){let a,l,c,u,f,d,h,p,m,g,y,v,b,_,w,x,k,q;const N=t-o,S=n-o,A=e-i,M=r-i;_=NM,d=LrN,h=d-(d-N),p=N-h,d=LrM,m=d-(d-M),g=M-m,w=pg-(_-hm-pm-hg),x=AS,d=LrA,h=d-(d-A),p=A-h,d=LrS,m=d-(d-S),g=S-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Gr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Gr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Gr[2]=v-(q-f)+(y-f),Gr[3]=q;let T=function(t,e){let n=e[0];for(let r=1;r<t;r++)n+=e[r];return n}(4,Gr),C=$rs;if(T>=C\|\|-T>=C)return T;if(f=t-N,a=t-(N+f)+(f-o),f=n-S,c=n-(S+f)+(f-o),f=e-A,l=e-(A+f)+(f-i),f=r-M,u=r-(M+f)+(f-i),0===a&&0===l&&0===c&&0===u)return T;if(C=Zrs+DrMath.abs(T),T+=Nu+Ma-(Ac+Sl),T>=C\|\|-T>=C)return T;_=aM,d=Lra,h=d-(d-a),p=a-h,d=LrM,m=d-(d-M),g=M-m,w=pg-(_-hm-pm-hg),x=lS,d=Lrl,h=d-(d-l),p=l-h,d=LrS,m=d-(d-S),g=S-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Hr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Hr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Hr[2]=v-(q-f)+(y-f),Hr[3]=q;const j=zr(4,Gr,4,Hr,Ur);_=Nu,d=LrN,h=d-(d-N),p=N-h,d=Lru,m=d-(d-u),g=u-m,w=pg-(_-hm-pm-hg),x=Ac,d=LrA,h=d-(d-A),p=A-h,d=Lrc,m=d-(d-c),g=c-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Hr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Hr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Hr[2]=v-(q-f)+(y-f),Hr[3]=q;const O=zr(j,Ur,4,Hr,Wr);_=au,d=Lra,h=d-(d-a),p=a-h,d=Lru,m=d-(d-u),g=u-m,w=pg-(_-hm-pm-hg),x=lc,d=Lrl,h=d-(d-l),p=l-h,d=Lrc,m=d-(d-c),g=c-m,k=pg-(x-hm-pm-hg),y=w-k,f=w-y,Hr[0]=w-(y+f)+(f-k),v=_+y,f=v-_,b=_-(v-f)+(y-f),y=b-x,f=b-y,Hr[1]=b-(y+f)+(f-x),q=v+y,f=q-v,Hr[2]=v-(q-f)+(y-f),Hr[3]=q;const E=zr(O,Wr,4,Hr,Jr);return Jr[E-1]}(t,e,n,r,o,i,c)}Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(8),Br(8),Br(8),Br(4),Br(8),Br(8),Br(8),Br(12);Br(192),Br(192);Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(8),Br(4),Br(4),Br(4),Br(8),Br(16),Br(16),Br(16),Br(32),Br(32),Br(48),Br(64);Br(1152),Br(1152);Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(4),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(24),Br(1152),Br(1152),Br(1152),Br(1152),Br(1152),Br(2304),Br(2304),Br(3456),Br(5760),Br(8),Br(8),Br(8),Br(16),Br(24),Br(48),Br(48),Br(96),Br(192),Br(384),Br(384),Br(384),Br(768);Br(96),Br(96),Br(96),Br(1152);const Yr=Math.pow(2,-52),Qr=new Uint32Array(512);class Kr{static from(t,e=oo,n=io){const r=t.length,o=new Float64Array(2r);for(let i=0;i<r;i++){const r=t[i];o[2i]=e(r),o[2i+1]=n(r)}return new Kr(o)}constructor(t){const e=t.length>>1;if(e>0&&"number"!=typeof t[0])throw new Error("Expected coords to contain numbers.");this.coords=t;const n=Math.max(2e-5,0);this._triangles=new Uint32Array(3n),this._halfedges=new Int32Array(3n),this._hashSize=Math.ceil(Math.sqrt(e)),this._hullPrev=new Uint32Array(e),this._hullNext=new Uint32Array(e),this._hullTri=new Uint32Array(e),this._hullHash=new Int32Array(this._hashSize).fill(-1),this._ids=new Uint32Array(e),this._dists=new Float64Array(e),this.update()}update(){const{coords:t,_hullPrev:e,_hullNext:n,_hullTri:r,_hullHash:o}=this,i=t.length>>1;let s=1/0,a=1/0,l=-1/0,c=-1/0;for(let e=0;e<i;e++){const n=t[2e],r=t[2e+1];n<s&&(s=n),r<a&&(a=r),n>l&&(l=n),r>c&&(c=r),this._ids[e]=e}const u=(s+l)/2,f=(a+c)/2;let d,h,p,m=1/0;for(let e=0;e<i;e++){const n=Xr(u,f,t[2e],t[2e+1]);n<m&&(d=e,m=n)}const g=t[2d],y=t[2d+1];m=1/0;for(let e=0;e<i;e++){if(e===d)continue;const n=Xr(g,y,t[2e],t[2e+1]);n<m&&n>0&&(h=e,m=n)}let v=t[2h],b=t[2h+1],_=1/0;for(let e=0;e<i;e++){if(e===d\|\|e===h)continue;const n=eo(g,y,v,b,t[2e],t[2e+1]);n<_&&(p=e,_=n)}let w=t[2p],x=t[2p+1];if(_===1/0){for(let e=0;e<i;e++)this._dists[e]=t[2e]-t[0]\|\|t[2e+1]-t[1];no(this._ids,this._dists,0,i-1);const e=new Uint32Array(i);let n=0;for(let t=0,r=-1/0;t<i;t++){const o=this._ids[t];this._dists[o]>r&&(e[n++]=o,r=this._dists[o])}return this.hull=e.subarray(0,n),this.triangles=new Uint32Array(0),void(this.halfedges=new Uint32Array(0))}if(Vr(g,y,v,b,w,x)<0){const t=h,e=v,n=b;h=p,v=w,b=x,p=t,w=e,x=n}const k=function(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=ss+aa,f=ll+cc,d=.5/(sc-al),h=t+(cu-af)d,p=e+(sf-lu)d;return{x:h,y:p}}(g,y,v,b,w,x);this._cx=k.x,this._cy=k.y;for(let e=0;e<i;e++)this._dists[e]=Xr(t[2e],t[2e+1],k.x,k.y);no(this._ids,this._dists,0,i-1),this._hullStart=d;let q=3;n[d]=e[p]=h,n[h]=e[d]=p,n[p]=e[h]=d,r[d]=0,r[h]=1,r[p]=2,o.fill(-1),o[this._hashKey(g,y)]=d,o[this._hashKey(v,b)]=h,o[this._hashKey(w,x)]=p,this.trianglesLen=0,this._addTriangle(d,h,p,-1,-1,-1);for(let i,s,a=0;a<this._ids.length;a++){const l=this._ids[a],c=t[2l],u=t[2l+1];if(a>0&&Math.abs(c-i)<=Yr&&Math.abs(u-s)<=Yr)continue;if(i=c,s=u,l===d\|\|l===h\|\|l===p)continue;let f=0;for(let t=0,e=this._hashKey(c,u);t<this._hashSize&&(f=o[(e+t)%this._hashSize],-1===f\|\|f===n[f]);t++);f=e[f];let m,g=f;for(;m=n[g],Vr(c,u,t[2g],t[2g+1],t[2m],t[2m+1])>=0;)if(g=m,g===f){g=-1;break}if(-1===g)continue;let y=this._addTriangle(g,l,n[g],-1,-1,r[g]);r[l]=this._legalize(y+2),r[g]=y,q++;let v=n[g];for(;m=n[v],Vr(c,u,t[2v],t[2v+1],t[2m],t[2m+1])<0;)y=this._addTriangle(v,l,m,r[l],-1,r[v]),r[l]=this._legalize(y+2),n[v]=v,q--,v=m;if(g===f)for(;m=e[g],Vr(c,u,t[2m],t[2m+1],t[2g],t[2g+1])<0;)y=this._addTriangle(m,l,g,-1,r[g],r[m]),this._legalize(y+2),r[m]=y,n[g]=g,q--,g=m;this._hullStart=e[l]=g,n[g]=e[v]=l,n[l]=v,o[this._hashKey(c,u)]=l,o[this._hashKey(t[2g],t[2g+1])]=g}this.hull=new Uint32Array(q);for(let t=0,e=this._hullStart;t<q;t++)this.hull[t]=e,e=n[e];this.triangles=this._triangles.subarray(0,this.trianglesLen),this.halfedges=this._halfedges.subarray(0,this.trianglesLen)}_hashKey(t,e){return Math.floor(function(t,e){const n=t/(Math.abs(t)+Math.abs(e));return(e>0?3-n:1+n)/4}(t-this._cx,e-this._cy)this._hashSize)%this._hashSize}_legalize(t){const{_triangles:e,_halfedges:n,coords:r}=this;let o=0,i=0;for(;;){const s=n[t],a=t-t%3;if(i=a+(t+2)%3,-1===s){if(0===o)break;t=Qr[--o];continue}const l=s-s%3,c=a+(t+1)%3,u=l+(s+2)%3,f=e[i],d=e[t],h=e[c],p=e[u];if(to(r[2f],r[2f+1],r[2d],r[2d+1],r[2h],r[2h+1],r[2p],r[2p+1])){e[t]=p,e[s]=f;const r=n[u];if(-1===r){let e=this._hullStart;do{if(this._hullTri[e]===u){this._hullTri[e]=t;break}e=this._hullPrev[e]}while(e!==this._hullStart)}this._link(t,r),this._link(s,n[i]),this._link(i,u);const a=l+(s+1)%3;o<Qr.length&&(Qr[o++]=a)}else{if(0===o)break;t=Qr[--o]}}return i}_link(t,e){this._halfedges[t]=e,-1!==e&&(this._halfedges[e]=t)}_addTriangle(t,e,n,r,o,i){const s=this.trianglesLen;return this._triangles[s]=t,this._triangles[s+1]=e,this._triangles[s+2]=n,this._link(s,r),this._link(s+1,o),this._link(s+2,i),this.trianglesLen+=3,s}}function Xr(t,e,n,r){const o=t-n,i=e-r;return oo+ii}function to(t,e,n,r,o,i,s,a){const l=t-s,c=e-a,u=n-s,f=r-a,d=o-s,h=i-a,p=uu+ff,m=dd+hh;return l(fm-ph)-c(um-pd)+(ll+cc)(uh-fd)<0}function eo(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=ss+aa,f=ll+cc,d=.5/(sc-al),h=(cu-af)d,p=(sf-lu)d;return hh+pp}function no(t,e,n,r){if(r-n<=20)for(let o=n+1;o<=r;o++){const r=t[o],i=e[r];let s=o-1;for(;s>=n&&e[t[s]]>i;)t[s+1]=t[s--];t[s+1]=r}else{let o=n+1,i=r;ro(t,n+r>>1,o),e[t[n]]>e[t[r]]&&ro(t,n,r),e[t[o]]>e[t[r]]&&ro(t,o,r),e[t[n]]>e[t[o]]&&ro(t,n,o);const s=t[o],a=e[s];for(;;){do{o++}while(e[t[o]]<a);do{i--}while(e[t[i]]>a);if(i<o)break;ro(t,o,i)}t[n+1]=t[i],t[i]=s,r-o+1>=i-n?(no(t,e,o,r),no(t,e,n,i-1)):(no(t,e,n,i-1),no(t,e,o,r))}}function ro(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function oo(t){return t[0]}function io(t){return t[1]}const so=1e-6;class ao{constructor(){this._x0=this._y0=this._x1=this._y1=null,this._=""}moveTo(t,e){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}`}closePath(){null!==this._x1&&(this._x1=this._x0,this._y1=this._y0,this._+="Z")}lineTo(t,e){this._+=`L${this._x1=+t},${this._y1=+e}`}arc(t,e,n){const r=(t=+t)+(n=+n),o=e=+e;if(n<0)throw new Error("negative radius");null===this._x1?this._+=`M${r},${o}`:(Math.abs(this._x1-r)>so\|\|Math.abs(this._y1-o)>so)&&(this._+="L"+r+","+o),n&&(this._+=`A${n},${n},0,1,1,${t-n},${e}A${n},${n},0,1,1,${this._x1=r},${this._y1=o}`)}rect(t,e,n,r){this._+=`M${this._x0=this._x1=+t},${this._y0=this._y1=+e}h${+n}v${+r}h${-n}Z`}value(){return this._\|\|null}}class lo{constructor(){this._=[]}moveTo(t,e){this._.push([t,e])}closePath(){this._.push(this._[0].slice())}lineTo(t,e){this._.push([t,e])}value(){return this._.length?this._:null}}class co{constructor(t,[e,n,r,o]=[0,0,960,500]){if(!((r=+r)>=(e=+e)&&(o=+o)>=(n=+n)))throw new Error("invalid bounds");this.delaunay=t,this._circumcenters=new Float64Array(2t.points.length),this.vectors=new Float64Array(2t.points.length),this.xmax=r,this.xmin=e,this.ymax=o,this.ymin=n,this._init()}update(){return this.delaunay.update(),this._init(),this}_init(){const{delaunay:{points:t,hull:e,triangles:n},vectors:r}=this,o=this.circumcenters=this._circumcenters.subarray(0,n.length/32);for(let e,r,i=0,s=0,a=n.length;i<a;i+=3,s+=2){const a=2n[i],l=2n[i+1],c=2n[i+2],u=t[a],f=t[a+1],d=t[l],h=t[l+1],p=t[c],m=t[c+1],g=d-u,y=h-f,v=p-u,b=m-f,_=2(gb-yv);if(Math.abs(_)<1e-9){let o=1e9;const i=2n[0];o=Math.sign((t[i]-u)b-(t[i+1]-f)v),e=(u+p)/2-ob,r=(f+m)/2+ov}else{const t=1/_,n=gg+yy,o=vv+bb;e=u+(bn-yo)t,r=f+(go-vn)t}o[s]=e,o[s+1]=r}let i,s,a,l=e[e.length-1],c=4l,u=t[2l],f=t[2l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],i=c,s=u,a=f,c=4l,u=t[2l],f=t[2l+1],r[i+2]=r[c]=a-f,r[i+3]=r[c+1]=u-s}render(t){const e=null==t?t=new ao:void 0,{delaunay:{halfedges:n,inedges:r,hull:o},circumcenters:i,vectors:s}=this;if(o.length<=1)return null;for(let e=0,r=n.length;e<r;++e){const r=n[e];if(r<e)continue;const o=2Math.floor(e/3),s=2Math.floor(r/3),a=i[o],l=i[o+1],c=i[s],u=i[s+1];this._renderSegment(a,l,c,u,t)}let a,l=o[o.length-1];for(let e=0;e<o.length;++e){a=l,l=o[e];const n=2Math.floor(r[l]/3),c=i[n],u=i[n+1],f=4a,d=this._project(c,u,s[f+2],s[f+3]);d&&this._renderSegment(c,u,d[0],d[1],t)}return e&&e.value()}renderBounds(t){const e=null==t?t=new ao:void 0;return t.rect(this.xmin,this.ymin,this.xmax-this.xmin,this.ymax-this.ymin),e&&e.value()}renderCell(t,e){const n=null==e?e=new ao:void 0,r=this._clip(t);if(null===r\|\|!r.length)return;e.moveTo(r[0],r[1]);let o=r.length;for(;r[0]===r[o-2]&&r[1]===r[o-1]&&o>1;)o-=2;for(let t=2;t<o;t+=2)r[t]===r[t-2]&&r[t+1]===r[t-1]\|\|e.lineTo(r[t],r[t+1]);return e.closePath(),n&&n.value()}cellPolygons(){const{delaunay:{points:t}}=this;for(let e=0,n=t.length/2;e<n;++e){const t=this.cellPolygon(e);t&&(t.index=e,yield t)}}cellPolygon(t){const e=new lo;return this.renderCell(t,e),e.value()}_renderSegment(t,e,n,r,o){let i;const s=this._regioncode(t,e),a=this._regioncode(n,r);0===s&&0===a?(o.moveTo(t,e),o.lineTo(n,r)):(i=this._clipSegment(t,e,n,r,s,a))&&(o.moveTo(i[0],i[1]),o.lineTo(i[2],i[3]))}contains(t,e,n){return(e=+e)==e&&(n=+n)==n&&this.delaunay._step(t,e,n)===t}neighbors(t){const e=this._clip(t);if(e)for(const n of this.delaunay.neighbors(t)){const t=this._clip(n);if(t)t:for(let r=0,o=e.length;r<o;r+=2)for(let i=0,s=t.length;i<s;i+=2)if(e[r]==t[i]&&e[r+1]==t[i+1]&&e[(r+2)%o]==t[(i+s-2)%s]&&e[(r+3)%o]==t[(i+s-1)%s]){yield n;break t}}}_cell(t){const{circumcenters:e,delaunay:{inedges:n,halfedges:r,triangles:o}}=this,i=n[t];if(-1===i)return null;const s=[];let a=i;do{const n=Math.floor(a/3);if(s.push(e[2n],e[2n+1]),a=a%3==2?a-2:a+1,o[a]!==t)break;a=r[a]}while(a!==i&&-1!==a);return s}_clip(t){if(0===t&&1===this.delaunay.hull.length)return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];const e=this._cell(t);if(null===e)return null;const{vectors:n}=this,r=4t;return n[r]\|\|n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,o,i,s,a=null,l=e[n-2],c=e[n-1],u=this._regioncode(l,c),f=0;for(let d=0;d<n;d+=2)if(r=l,o=c,l=e[d],c=e[d+1],i=u,u=this._regioncode(l,c),0===i&&0===u)s=f,f=0,a?a.push(l,c):a=[l,c];else{let e,n,d,h,p;if(0===i){if(null===(e=this._clipSegment(r,o,l,c,i,u)))continue;[n,d,h,p]=e}else{if(null===(e=this._clipSegment(l,c,r,o,u,i)))continue;[h,p,n,d]=e,s=f,f=this._edgecode(n,d),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(n,d):a=[n,d]}s=f,f=this._edgecode(h,p),s&&f&&this._edge(t,s,f,a,a.length),a?a.push(h,p):a=[h,p]}if(a)s=f,f=this._edgecode(a[0],a[1]),s&&f&&this._edge(t,s,f,a,a.length);else if(this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2))return[this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax,this.xmin,this.ymin];return a}_clipSegment(t,e,n,r,o,i){for(;;){if(0===o&&0===i)return[t,e,n,r];if(o&i)return null;let s,a,l=o\|\|i;8&l?(s=t+(n-t)(this.ymax-e)/(r-e),a=this.ymax):4&l?(s=t+(n-t)(this.ymin-e)/(r-e),a=this.ymin):2&l?(a=e+(r-e)(this.xmax-t)/(n-t),s=this.xmax):(a=e+(r-e)(this.xmin-t)/(n-t),s=this.xmin),o?(t=s,e=a,o=this._regioncode(t,e)):(n=s,r=a,i=this._regioncode(n,r))}}_clipInfinite(t,e,n,r,o,i){let s,a=Array.from(e);if((s=this._project(a[0],a[1],n,r))&&a.unshift(s[0],s[1]),(s=this._project(a[a.length-2],a[a.length-1],o,i))&&a.push(s[0],s[1]),a=this._clipFinite(t,a))for(let e,n=0,r=a.length,o=this._edgecode(a[r-2],a[r-1]);n<r;n+=2)e=o,o=this._edgecode(a[n],a[n+1]),e&&o&&(n=this._edge(t,e,o,a,n),r=a.length);else this.contains(t,(this.xmin+this.xmax)/2,(this.ymin+this.ymax)/2)&&(a=[this.xmin,this.ymin,this.xmax,this.ymin,this.xmax,this.ymax,this.xmin,this.ymax]);return a}_edge(t,e,n,r,o){for(;e!==n;){let n,i;switch(e){case 5:e=4;continue;case 4:e=6,n=this.xmax,i=this.ymin;break;case 6:e=2;continue;case 2:e=10,n=this.xmax,i=this.ymax;break;case 10:e=8;continue;case 8:e=9,n=this.xmin,i=this.ymax;break;case 9:e=1;continue;case 1:e=5,n=this.xmin,i=this.ymin}r[o]===n&&r[o+1]===i\|\|!this.contains(t,n,i)\|\|(r.splice(o,0,n,i),o+=2)}if(r.length>4)for(let t=0;t<r.length;t+=2){const e=(t+2)%r.length,n=(t+4)%r.length;(r[t]===r[e]&&r[e]===r[n]\|\|r[t+1]===r[e+1]&&r[e+1]===r[n+1])&&(r.splice(e,2),t-=2)}return o}_project(t,e,n,r){let o,i,s,a=1/0;if(r<0){if(e<=this.ymin)return null;(o=(this.ymin-e)/r)<a&&(s=this.ymin,i=t+(a=o)n)}else if(r>0){if(e>=this.ymax)return null;(o=(this.ymax-e)/r)<a&&(s=this.ymax,i=t+(a=o)n)}if(n>0){if(t>=this.xmax)return null;(o=(this.xmax-t)/n)<a&&(i=this.xmax,s=e+(a=o)r)}else if(n<0){if(t<=this.xmin)return null;(o=(this.xmin-t)/n)<a&&(i=this.xmin,s=e+(a=o)r)}return[i,s]}_edgecode(t,e){return(t===this.xmin?1:t===this.xmax?2:0)\|(e===this.ymin?4:e===this.ymax?8:0)}_regioncode(t,e){return(t<this.xmin?1:t>this.xmax?2:0)\|(e<this.ymin?4:e>this.ymax?8:0)}}const uo=2Math.PI,fo=Math.pow;function ho(t){return t[0]}function po(t){return t[1]}function mo(t,e,n){return[t+Math.sin(t+e)n,e+Math.cos(t-e)n]}class go{static from(t,e=ho,n=po,r){return new go("length"in t?function(t,e,n,r){const o=t.length,i=new Float64Array(2o);for(let s=0;s<o;++s){const o=t[s];i[2s]=e.call(r,o,s,t),i[2s+1]=n.call(r,o,s,t)}return i}(t,e,n,r):Float64Array.from(function(t,e,n,r){let o=0;for(const i of t)yield e.call(r,i,o,t),yield n.call(r,i,o,t),++o}(t,e,n,r)))}constructor(t){this._delaunator=new Kr(t),this.inedges=new Int32Array(t.length/2),this._hullIndex=new Int32Array(t.length/2),this.points=this._delaunator.coords,this._init()}update(){return this._delaunator.update(),this._init(),this}_init(){const t=this._delaunator,e=this.points;if(t.hull&&t.hull.length>2&&function(t){const{triangles:e,coords:n}=t;for(let t=0;t<e.length;t+=3){const r=2e[t],o=2e[t+1],i=2e[t+2];if((n[i]-n[r])(n[o+1]-n[r+1])-(n[o]-n[r])(n[i+1]-n[r+1])>1e-10)return!1}return!0}(t)){this.collinear=Int32Array.from({length:e.length/2},((t,e)=>e)).sort(((t,n)=>e[2t]-e[2n]\|\|e[2t+1]-e[2n+1]));const t=this.collinear[0],n=this.collinear[this.collinear.length-1],r=[e[2t],e[2t+1],e[2n],e[2n+1]],o=1e-8Math.hypot(r[3]-r[1],r[2]-r[0]);for(let t=0,n=e.length/2;t<n;++t){const n=mo(e[2t],e[2t+1],o);e[2t]=n[0],e[2t+1]=n[1]}this._delaunator=new Kr(e)}else delete this.collinear;const n=this.halfedges=this._delaunator.halfedges,r=this.hull=this._delaunator.hull,o=this.triangles=this._delaunator.triangles,i=this.inedges.fill(-1),s=this._hullIndex.fill(-1);for(let t=0,e=n.length;t<e;++t){const e=o[t%3==2?t-2:t+1];-1!==n[t]&&-1!==i[e]\|\|(i[e]=t)}for(let t=0,e=r.length;t<e;++t)s[r[t]]=t;r.length<=2&&r.length>0&&(this.triangles=new Int32Array(3).fill(-1),this.halfedges=new Int32Array(3).fill(-1),this.triangles[0]=r[0],i[r[0]]=1,2===r.length&&(i[r[1]]=0,this.triangles[1]=r[1],this.triangles[2]=r[1]))}voronoi(t){return new co(this,t)}neighbors(t){const{inedges:e,hull:n,_hullIndex:r,halfedges:o,triangles:i,collinear:s}=this;if(s){const e=s.indexOf(t);return e>0&&(yield s[e-1]),void(e<s.length-1&&(yield s[e+1]))}const a=e[t];if(-1===a)return;let l=a,c=-1;do{if(yield c=i[l],l=l%3==2?l-2:l+1,i[l]!==t)return;if(l=o[l],-1===l){const e=n[(r[t]+1)%n.length];return void(e!==c&&(yield e))}}while(l!==a)}find(t,e,n=0){if((t=+t)!=t\|\|(e=+e)!=e)return-1;const r=n;let o;for(;(o=this._step(n,t,e))>=0&&o!==n&&o!==r;)n=o;return o}_step(t,e,n){const{inedges:r,hull:o,_hullIndex:i,halfedges:s,triangles:a,points:l}=this;if(-1===r[t]\|\|!l.length)return(t+1)%(l.length>>1);let c=t,u=fo(e-l[2t],2)+fo(n-l[2t+1],2);const f=r[t];let d=f;do{let r=a[d];const f=fo(e-l[2r],2)+fo(n-l[2r+1],2);if(f<u&&(u=f,c=r),d=d%3==2?d-2:d+1,a[d]!==t)break;if(d=s[d],-1===d){if(d=o[(i[t]+1)%o.length],d!==r&&fo(e-l[2d],2)+fo(n-l[2d+1],2)<u)return d;break}}while(d!==f);return c}render(t){const e=null==t?t=new ao:void 0,{points:n,halfedges:r,triangles:o}=this;for(let e=0,i=r.length;e<i;++e){const i=r[e];if(i<e)continue;const s=2o[e],a=2o[i];t.moveTo(n[s],n[s+1]),t.lineTo(n[a],n[a+1])}return this.renderHull(t),e&&e.value()}renderPoints(t,e){void 0!==e\|\|t&&"function"==typeof t.moveTo\|\|(e=t,t=null),e=null==e?2:+e;const n=null==t?t=new ao:void 0,{points:r}=this;for(let 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o=t.selection?t.selection():t;o.property("__zoom",Xp),t!==o?w(t,e,n,r):o.interrupt().each((function(){x(this,arguments).event(r).start().zoom(null,"function"==typeof e?e.apply(this,arguments):e).end()}))},y.scaleBy=function(t,e,n,r){y.scaleTo(t,(function(){return this.__zoom.k("function"==typeof e?e.apply(this,arguments):e)}),n,r)},y.scaleTo=function(t,e,n,r){y.transform(t,(function(){var t=o.apply(this,arguments),r=this.__zoom,s=null==n?_(t):"function"==typeof n?n.apply(this,arguments):n,a=r.invert(s),l="function"==typeof e?e.apply(this,arguments):e;return i(b(v(r,l),s,a),t,c)}),n,r)},y.translateBy=function(t,e,n,r){y.transform(t,(function(){return i(this.__zoom.translate("function"==typeof e?e.apply(this,arguments):e,"function"==typeof n?n.apply(this,arguments):n),o.apply(this,arguments),c)}),null,r)},y.translateTo=function(t,e,n,r,s){y.transform(t,(function(){var t=o.apply(this,arguments),s=this.__zoom,a=null==r?_(t):"function"==typeof r?r.apply(this,arguments):r;return 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