@sjcrh/proteinpaint-server 2.14.4 → 2.16.0

package/server.js

@@ -1,2 +1 @@
-/*! For license information please see server.js.LICENSE.txt */
-(()=>{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 for intragenic deletion";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("gene");if(-1==o)return"gene missing from header";if(n[o]="gene",o=r("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==o)return"isoform missing from header";if(n[o]="isoform",o=r("rnaposition"),-1!=o){if(n[o]="rnaposition",o=r("rnadellength"),-1==o)return"rnadellength is required when rnaPosition is used";n[o]="rnadellength"}if(o=r("chromosome","chr"),-1!=o){if(n[o]="chr",o=r("chr_start"),-1==o)return"chr_start is required when chr is used";if(n[o]="chrpos1",o=r("chr_stop"),-1==o)return"chr_stop is required when chr is used";n[o]="chrpos2"}return 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 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value",i]);s.chrpos2=e}if(!o.parsesample(s,n,t,i,n.del.badlines)){s.dt=r.dtdel,s.class=r.mclassdel,s.mname="DEL",n.good++;var a=n.geneToUpper?s.gene.toUpperCase():s.gene;a in n.data||(n.data[a]=[]),n.data[a].push(s)}}else n.del.badlines.push([t,"missing gene",i])}},3602:(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 for ITD";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("gene");if(-1==o)return"gene missing from header";if(n[o]="gene",o=r("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==o)return"isoform missing from header";if(n[o]="isoform",o=r("rnaposition"),-1!=o){if(n[o]="rnaposition",o=r("rnaduplength"),-1==o)return"rnaduplength is required when rnaposition is 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value",i]);if(e=Number.parseInt(s.rnaduplength),Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid rnaDuplength value",i]);s.rnaduplength=e}if(s.chr){let e=Number.parseInt(s.chrpos1);if(Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid chr_start value",i]);if(s.chrpos1=e,e=Number.parseInt(s.chrpos2),Number.isNaN(e)||e<0)return void n.itd.badlines.push([t,"invalid chr_stop value",i]);s.chrpos2=e}if(!o.parsesample(s,n,t,i,n.itd.badlines)){s.dt=r.dtitd,s.class=r.mclassitd,s.mname="ITD",n.good++;var a=n.geneToUpper?s.gene.toUpperCase():s.gene;a in n.data||(n.data[a]=[]),n.data[a].push(s)}}else n.itd.badlines.push([t,"missing gene",i])}},8064:(t,e,n)=>{"use strict";n.r(e),n.d(e,{default:()=>o,init_bulk_flag:()=>i,parsesample:()=>s});var r=n(2273);const o={};function i(t){if(!t)return null;const e={};for(const t in r.mclass)e[r.mclass[t].label.toUpperCase()]=t;return{genome:t,mclasslabel2key:e,data:{},sample2disease:{},patient2st:{},good:0,geneToUpper:!0,snv:{loaded:!1,header:null,badlines:[],missense:0,silent:0},svjson:{loaded:!1,header:null,badlines:[]},fusion:{loaded:!1,header:null,badlines:[],original:[]},sv:{loaded:!1,header:null,badlines:[],original:[]},cnv:{loaded:!1,header:null,badlines:[]},itd:{loaded:!1,header:null,badlines:[]},del:{loaded:!1,header:null,badlines:[]},truncation:{loaded:!1,header:null,badlines:[]}}}function s(t,e,n,o,i){let s=r.moriginsomatic;if(t.sampletype){switch(t.sampletype.toLowerCase()){case"relapse":s=r.moriginrelapse;break;case"germline":s=r.morigingermline}t.sample?t.patient||(t.patient=t.sample+" "+t.sampletype):t.patient&&(t.sample=t.patient+" "+t.sampletype)}else t.patient?t.sample?t.sampletype=t.sample:t.sample=t.sampletype=t.patient:t.sample&&(t.sampletype=t.sample);if(t.origin)switch(t.origin.toLowerCase()){case"r":case"relapse":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+'": '+t.disease+", "+e.sample2disease[t.sample],o]),!0}else e.sample2disease[t.sample]=t.disease;return!1}},5494:(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 snv/indel";const r=(...t)=>{for(const e of t){const t=n.indexOf(e);if(-1!=t)return t}return-1};let o=r("annovar_gene","annovar_sj_gene","gene","genename","gene_symbol","hugo_symbol");return-1==o?"gene missing from header":(n[o]="gene",o=r("annovar_aachange","amino_acid_change","annovar_sj_aachange","aachange","protein_change","variant"),-1==o?"amino_acid_change missing from header":(n[o]="mname",o=r("annovar_class","class","mclass","variant_class","variant_classification","annovar_sj_class"),-1==o?"variant_class missing from header":(n[o]="class",o=r("chromosome","chr"),-1==o?"chromosome missing from header":(n[o]="chr",o=r("wu_hg19_pos","start","start_position","chr_position","position"),-1==o?"start missing from header":(n[o]="pos",o=r("annovar_isoform","mrna_accession","mrna accession","refseq_mrna_id","annovar_sj_filter_isoform","refseq","isoform"),-1==o?"isoform missing from header":(n[o]="isoform",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("quantitative_measurements"),-1!=o&&(n[o]="qmset"),o=r("mutant_reads_in_case","mutant_in_tumor","tumor_readcount_alt"),-1!=o&&(n[o]="maf_tumor_v1"),o=r("total_reads_in_case","total_in_tumor","tumor_readcount_total"),-1!=o&&(n[o]="maf_tumor_v2"),o=r("mutant_reads_in_control","mutant_in_normal","normal_readcount_alt"),-1!=o&&(n[o]="maf_normal_v1"),o=r("total_reads_in_control","total_in_normal","normal_readcount_total"),-1!=o&&(n[o]="maf_normal_v2"),o=r("cdna_change"),-1!=o&&(n[o]="cdna_change"),o=r("sampletype","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 maf_normal mutant and/or total read count",i]);s.maf_normal={f:e/r,v1:e,v2:r}}delete s.maf_normal_v1,delete s.maf_normal_v2}n.good++,"M"==s.class?n.snv.missense++:"S"==s.class&&n.snv.silent++;const c=n.geneToUpper?s.gene.toUpperCase():s.gene;n.data[c]||(n.data[c]=[]),s.dt=r.dtsnvindel,n.data[c].push(s)}},6279:(t,e,n)=>{"use strict";n.r(e),n.d(e,{duplicate:()=>a,parseheader:()=>i,parseline:()=>s});var r=n(8064),o=n(2273);function i(t,e,n){const r=t.toLowerCase().split("\t");if(r.length<=1)return"invalid file header for fusions";const o=(...t)=>{for(const e of t){const t=r.indexOf(e);if(-1!=t)return t}return-1};let i=o("gene_a","gene1","genea");return-1==i?"gene_a missing from header":(r[i]="gene1",i=o("gene_b","gene2","geneb"),-1==i?"gene_b missing from header":(r[i]="gene2",i=o("chr_a","chr1","chra"),-1==i?"chr_a missing from header":(r[i]="chr1",i=o("chr_b","chr2","chrb"),-1==i?"chr_b missing from header":(r[i]="chr2",i=o("pos_a","position_a","position1","posa"),-1==i?"pos_a missing from 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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 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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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 jt(t,e,n){if(n.query.isoform&&gt[n.query.genome].genomicNameRegexp.test(n.query.isoform))return;const[r,o]=e.makequery(n.query);if(!r)return;const i=t.newconn.prepare(r).all(o);let s;s=e.tidy?i.map((t=>e.tidy(t))):i;const a={};if(e.isgeneexpression){a.lst=s,a.isgeneexpression=!0,a.config=e.config;for(const e of t.queries)if(e.dsblocktracklst)for(const t of e.dsblocktracklst)t.type==k.tkt.junction&&(a.config.dsjunctiontk=t)}else a.lst=s;return a}function Ot(t,e){const n=[u.join(o.tpmasterdir,t.vcffile),(t.vcf.nochr?e.query.range.chr.replace("chr",""):e.query.range.chr)+":"+e.query.range.start+"-"+e.query.range.stop];return new Promise(((e,r)=>{const o=m(yt,n),i=[],s=[];o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>s.push(t))),o.on("close",(n=>{""!=s.join("").trim()&&r("error querying vcf file");const o=i.join("").trim();e({lines:""==o?[]:o.split("\n"),vcfid:t.vcf.vcfid})}))}))}function Et(t){if(!t.genome)return["no genome"];const e=gt[t.genome];if(!e)return["invalid 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r=Ut(e,t,i.checkrnabam);r&&r.dnacount.ishet&&n.hetsnps.push(r)}if(n.url?n.dir=await x.cache_index(n.url,n.indexURL||n.url+".bai"):n.file&&(n.file=u.join(o.tpmasterdir,n.file)),n.hetsnps.length>0){await Ft(n,n.hetsnps,e,i.checkrnabam);for(const e of n.hetsnps)e.rnacount.nocoverage||e.rnacount.ref+e.rnacount.alt<i.checkrnabam.rna_mintotalreads||l.push(t+"."+e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt)}}l.length>0&&await async function(t,e){const n=await function(t){const e=u.join(o.cachedir,Math.random().toString());return new Promise(((n,r)=>{c.writeFile(e,t.join("\n")+"\n",(t=>{t&&r("cannot write"),n(e)}))}))}(t),r=await $t(n);await function(t,e){return new Promise(((n,r)=>{c.readFile(t,"utf8",((t,o)=>{if(t&&r("cannot read binom pvalue"),o){for(const t of o.trim().split("\n")){const n=t.split("\t"),r=n[0].split("."),o=e[r[0]];if(!o)continue;const i=o.hetsnps.find((t=>t.pos+"."+t.ref+"."+t.alt==r[1]+"."+r[2]+"."+r[3]));i&&(i.rnacount.pvalue=Number.parseFloat(n[10]))}n()}else n()}))}))}(r,e),c.unlink(n,(()=>{})),c.unlink(r,(()=>{}))}(l,i.checkrnabam.samples),s.checkrnabam=[];for(const n in i.checkrnabam.samples){const r=i.checkrnabam.samples[n],o=[];for(const[n,s]of t){const t={gene:n,chr:e,start:s.start,stop:s.stop},a=r.hetsnps.filter((t=>t.pos>=s.start&&t.pos<=s.stop)),l=a.filter((t=>!t.rnacount.nocoverage));if(l.length>0){const e=l.reduce(((t,e)=>t+Math.abs(e.rnacount.f-.5)),0);let n=null,r=0;for(const t of l)null!=t.rnacount.pvalue&&(null==n?n=t.rnacount.pvalue:n*=t.rnacount.pvalue,t.rnacount.pvalue<=i.checkrnabam.binompvaluecutoff&&r++);null!=n&&(t.ase={markers:a.filter((t=>t.dnacount.ishet)).length,ase_markers:r,mean_delta:e/l.length,geometricmean:Math.pow(n,1/l.length)})}let c;c=r.pairedend?await Pt(r,e,s):await It(r,e,s),t.fpkm=1e9*c/(r.totalreads*s.exonlength),t.snps=a,o.push(t)}o.length&&s.checkrnabam.push({sample:n,genes:o})}}async function It(t,e,n){const r=["view","-c","-M",t.url||t.file];for(const o of n.exonunion)r.push((t.nochr?e.replace("chr",""):e)+":"+(o[0]+1)+"-"+(o[1]+1));let o;return await x.get_lines_bigfile({isbam:!0,args:r,dir:t.dir,callback:t=>o=t}),Number.parseInt(o)}function Pt(t,e,n){return new Promise(((r,o)=>{const i=["view","-M",t.url||t.file];for(const r of n.exonunion)i.push((t.nochr?e.replace("chr",""):e)+":"+(r[0]+1)+"-"+(r[1]+1));const s=m(bt,i,{cwd:t.dir}),a=m("cut",["-f1"],{cwd:t.dir}),l=m("sort",["-u"],{cwd:t.dir}),c=m("wc",["-l"],{cwd:t.dir});s.stdout.pipe(a.stdin),a.stdout.pipe(l.stdin),l.stdout.pipe(c.stdin);const u=[],f=[];c.stdout.on("data",(t=>u.push(t))),c.stderr.on("data",(t=>f.push(t))),c.on("close",(()=>{r(Number.parseInt(u.join("")))}))}))}function Ft(t,e,n,r){const o=[];for(const r of 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(vt,["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 Dt(t,e,n,r,o,i){e.hideLOHwithCNVoverlap&&Lt(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)Bt(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)Bt(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 grouping samples from vcf: "+e.dt);else for(const n of e.sampledata){let e=!0;for(const r of t)if(r.samplename==n.sampleobj.name){e=!1;break}e&&t.push({samplename:n.sampleobj.name,items:[]})}t.length&&s.push({samples:t})}return s}function Lt(t){for(const[e,n]of t){const r=new Map,o=new Map,i=[];for(const t of n)t.dt!=k.dtloh?(t.dt==k.dtcnv&&(o.has(t.chr)||o.set(t.chr,[]),o.get(t.chr).push(t)),i.push(t)):(r.has(t.chr)||r.set(t.chr,[]),r.get(t.chr).push(t));if(0!=r.size){for(const[t,e]of r){const n=o.get(t);if(n)for(const t of e){let e=!0;for(const r of n)if(Math.max(t.start,r.start)<Math.min(t.stop,r.stop)){e=!1;break}e&&i.push(t)}else for(const t of e)i.push(t)}t.set(e,i)}}}function Bt(t,e,n,r,o,i){const s=o.cohort.annotation[t];if(!s)return void r.push({samplename:t,items:e});const a=s[i.groupsamplebyattr.attrlst[0].k];if(null==a)return void r.push({samplename:t,items:e});const l=[];for(let t=1;t<i.groupsamplebyattr.attrlst.length;t++){const 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 zt(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 Ut(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 Gt(t,e,n,r,i){const s=await Ht(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 Ht(t,e,n){return new Promise(((r,o)=>{const i=m(yt,[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 Vt(t,e){return new Promise(((n,r)=>{const o=m(yt,["-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 Jt(t,e){const n=e.findIndex((e=>e.value>=t));return-1==n||n==e.length-1?100:0==n?0:Math.ceil(100*n/e.length)}function Wt(t,e,n){return t.key?e.cohort?e.cohort.annotation?[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}}))]:["ds.cohort.annotation missing"]:["ds.cohort missing"]:[".key missing"]}function Yt(t,e,n,i){if(!t.genename)return["genename missing"];const s=t.genename.toLowerCase();return t.chr?Number.isInteger(t.start)&&Number.isInteger(t.stop)?t.stop-t.start>1e7?["gene feature too long (> 10Mb)"]:[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(yt,[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)}))}))))]:["invalid start/stop coordinate"]:["chr missing"]}function Kt(t,e,n,i){return t.chr?Number.isInteger(t.start)&&Number.isInteger(t.stop)?t.stop-t.start>1e7?["look range too big (>10Mb)"]:null==t.valuecutoff||Number.isFinite(t.valuecutoff)?null==t.focalsizelimit||Number.isInteger(t.focalsizelimit)?[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(yt,[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)}))}))))]:["invalid value for focalsizelimit"]:["invalid value for valuecutoff"]:["invalid start/stop coordinate"]:["chr missing"]}function Xt(t,e,n,i){return t.chr?Number.isInteger(t.start)&&Number.isInteger(t.stop)?t.stop-t.start>1e7?["look range too big (>10Mb)"]:null==t.valuecutoff||Number.isFinite(t.valuecutoff)?null==t.focalsizelimit||Number.isInteger(t.focalsizelimit)?[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(yt,[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)}))}))))]:["invalid value for focalsizelimit"]:["invalid value for valuecutoff"]:["invalid start/stop coordinate"]:["chr 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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&&Lt(i);const c=[];for(const[t,e]of i)for(const t of e)c.push(t);s({id:t.id,items:c})}))}))))]:["invalid start/stop coordinate"]:["chr missing"]}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 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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=gt[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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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]=ae(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:v(r)})}catch(n){e.send({error:n.message||n})}})),kt.post(qt+"/svmr",(function(t,e){if(t.query.file){const[n,r,o]=ae(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(se(t.query.file))throw"invalid file path";const r=u.join(o.tpmasterdir,t.query.file.endsWith(".json")?t.query.file:t.query.file+".json"),i=JSON.parse(await x.read_file(r));if(!i.genome)throw"genome missing";const s={};let a=0;for(const t of i.mutationset||[]){const e=N.init_bulk_flag(i.genome);if(!e)throw"init_bulk_flag() failed";if(i.mutationset.length>1&&(e.tpsetname=t.name?t.name:"set"+ ++a),s[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(i.annotations){const t=i.annotations.idkey?i.annotations.idkey:"sample";i.annotations.data={};for(const e of i.annotations.files){const n=await x.read_file(u.join(o.tpmasterdir,e));R.tsvParse(n).forEach((e=>{const n=e[t].trim();i.annotations.data[n]||(i.annotations.data[n]=[]),i.annotations.data[n].push(e)}))}}for(const t in s)delete(n=s[t]).mclasslabel2key,delete n.sample2disease,delete n.patient2ori2sample;delete i.mutationset,e.send({cohort:i,flagset:s})}catch(t){return void e.send({error:t.message||t})}var n})),kt.post(qt+"/textfile",(function(t,e){if(!t.query.file)return e.send({error:"no file"});if(se(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",H),kt.post(qt+"/mdsjunction",z(gt)),kt.post(qt+"/mdscnv",(function(t,e){const[n,i,s,a]=Et(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&&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(yt,[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].Unannotated){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.barheight*Math.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.barheight*Math.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(["Unannotated",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=gt[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=zt(t.query.checkrnabam);if(r)return n.send({error:r});a.checkrnabam=t.query.checkrnabam}}else{if(i=gt[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;return t.query.iscustom?e.send({error:"no server-side config available for custom track"}):n.sampleAssayTrack?e.send({tracks:n.sampleAssayTrack.samples.get(r)}):e.send({})}(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()})}!function(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))}}(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})}(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 Set(t.query.skip_termids||[]),o=new Map;for(const e in n.cohort.annotation)t.query.key&&n.cohort.annotation[e][t.query.key]!=t.query.value||o.set(e,new Map);for(const[t,e]of o){const o=n.assayAvailability.samples.get(t);if(o)for(const t of n.assayAvailability.assays)r.has(t.id)||o[t.id]&&e.set(t.id,"yes")}for(const t of o.keys())0==o.get(t).size&&o.delete(t);const i={};i.totalsample=o.size,i.terms=rt({sample2term:o,terms:n.assayAvailability.assays,config:{termidorder:t.query.termidorder}}),e.send(i)}catch(t){e.send({error:t.message||t})}}(t,n,s);if(!s.queries)return n.send({error:"dataset is not equipped with queries"});if(a=s.queries[t.query.querykey],!a)return n.send({error:"invalid querykey"})}if(t.query.getexpression4gene)return async function(t,e,n,r,i){try{const n=t.query.getexpression4gene;if(!n.chr)throw"chr missing";if(!Number.isFinite(n.start))throw"invalid start pos";if(!Number.isFinite(n.stop))throw"invalid stop pos";if(!n.name)throw"unknown gene name";if(i.checkrnabam){const r=gt[t.query.genome],o=r.tracks.find((t=>t.__isgene)),s=(await Gt(0,o,n.chr,n.start,n.stop)).get(n.name);if(!s)throw"no gene matching with "+n.name;const a={};await Rt(new Map([[n.name,s]]),n.chr,n.start,n.stop,i,a);const l={};for(const t of a.checkrnabam)if(t.genes){const e=t.genes.find((t=>t.gene==n.name));e&&(l[t.sample]=e)}return void e.send({sample2rnabam:l})}let s;if(i.iscustom?s=i.checkexpressionrank:i.expressionrank_querykey&&(s=r.queries[i.expressionrank_querykey]),!s)throw"missing expression data source";const a=s.file?null:await x.cache_index(s.url,s.indexURL),l=[];await x.get_lines_bigfile({args:[s.file?u.join(o.tpmasterdir,s.file):s.url,n.chr+":"+n.start+"-"+n.stop],dir:a,callback:t=>{const e=t.split("\t");let r;try{r=JSON.parse(e[3])}catch(t){reject("invalid json from expression data")}r.sample&&r.gene&&Number.isFinite(r.value)&&(delete r.outlier,r.gene.toLowerCase()==n.name.toLowerCase()&&l.push(r))}});const c=function(t,e,n){const r={};if(t&&t.cohort&&t.cohort.annotation&&e.groupsamplebyattr&&e.groupsamplebyattr.attrlst){const o=new Map;for(const r of n){const n=t.cohort.annotation[r.sample];if(!n)continue;const i=[];for(const t of e.groupsamplebyattr.attrlst)i.push(n[t.k]);const s=i.join(",");o.has(s)||o.set(s,[]),o.get(s).push(r)}for(const t of o.values()){t.sort(((t,e)=>t.value-e.value));for(const e of t)e.rank=Jt(e.value,t),r[e.sample]=e}}else{n.sort(((t,e)=>t.value-e.value));for(const t of n)t.rank=Jt(t.value,n),r[t.sample]=t}return r}(r,i,l);e.send({sample2rank:c})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}}(t,n,0,s,a);if(t.query.ifsamplehasvcf)return function(t,e,n,r,o){if(t.query.iscustom)return e.send({no:1});if(!o.vcf_querykey)return e.send({yes:1});const i=r.queries[o.vcf_querykey];if(!i)return e.send({error:"vcf query 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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]=ae(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=gt[t.query.genome];if(!n)throw"invalid genome";const[r,o,i]=ae(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=gt[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]=ae(t);if(n)throw"illegal file name";o||await x.file_is_readable(r);const i=await ot(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]=ae(t);if(n)return void e.send({error:"illegal file 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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[n,i]=Yt(e,0,t,r);if(n)throw"error with isgenevalue: "+n;o.push(i)}else if(e.iscnv){const[n,i]=Kt(e,0,t,r);if(n)throw"error with iscnv: "+n;o.push(i)}else if(e.isloh){const[n,i]=Xt(e,0,t,r);if(n)throw"error with isloh: "+n;o.push(i)}else if(e.isvcf){const[n,i]=re(e,0,t,r);if(n)throw"error with isvcf: "+n;o.push(i)}else if(e.isitd){const[n,i]=Qt(e,0,t,r);if(n)throw"error with isitd: "+n;o.push(i)}else if(e.issvfusion){const[n,i]=te(e,0,t,r);if(n)throw"error with issvfusion: "+n;o.push(i)}else if(e.issvcnv){const[n,i]=ee(e,0,t,r);if(n)throw"error with issvcnv: "+n;o.push(i)}else if(e.ismutation){const[t,n]=ne(e,0,i,r);if(t)throw"error with ismutation: "+t;o.push(n)}else{if(!e.issampleattribute)throw"unknown type of feature";{const[t,i]=Wt(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=gt[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",at(gt)),kt.post(qt+"/fimo",nt.handle_closure(gt)),kt.all(qt+"/termdb",P.handle_request_closure(gt)),kt.all(qt+"/termdb-barsql",D.handle_request_closure(gt)),kt.post(qt+"/singlecell",et.handle_singlecell_closure(gt)),kt.post(qt+"/massSession",tt.save),kt.get(qt+"/massSession",tt.get),kt.get(qt+"/isoformbycoord",(async function(t,e){try{const n=gt[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=gt[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=zt(n.checkrnabam);if(s)throw 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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=v),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.width*t.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;return n-e<=t.width?(u=!0,l=1,c=t.width/(n-e),a.lineWidth=c):(c=1,l=(n-e)/t.width),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 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Promise(((t,r)=>{c.writeFile(e,n.join("\n")+"\n",(n=>{n&&r("cannot write"),t(e)}))}))}(n),i=await $t(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,(()=>{}))}(b,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}(b,l,n);let N=0;for(const t of b)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=gt[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=gt[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=gt[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"}}(),wt=function(){const t=c.statSync(o.binpath+"/server.js").mtime,e=c.existsSync("public/bin/proteinpaint.js")&&c.statSync("public/bin/proteinpaint.js").mtime||0;return t>e?t:e}(),xt=Date(Date.now()).toString().split(" ").slice(0,5).join(" "),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";if(o.cachedir_massSession=await fe("massSession"),o.cachedir_massSessionTrash=await fe("massSessionTrash"),o.cache_snpgt={dir:await fe("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},o.cachedir_bam=await fe("bam"),o.cachedir_genome=await fe("genome"),o.cachedir_ssid=await fe("ssid"),o.commonOverrides&&k.applyOverrides(o.commonOverrides),!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);if(gt[t.name]=n,!n.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==n.genomefile||(n.genomefile=u.join(o.tpmasterdir,n.genomefile)),n.genomicNameRegexp||(n.genomicNameRegexp=/[^a-zA-Z0-9.:_-]/),n.tracks||(n.tracks=[]),t.tracks)for(const e of t.tracks)n.tracks.push(e);if(t.datasets&&(n.rawdslst=t.datasets),t.snp&&(n.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;n.blat=t.blat}if(t.nosnp&&delete n.snp,t.nohicenzyme&&delete n.hicenzymefragment,t.nohicdomain&&delete n.hicdomain,n.genedb&&t.no_gene2canonicalisoform&&delete n.genedb.gene2canonicalisoform,t.updateAttr)for(const e of t.updateAttr){let t=n;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&&gt[o.defaultgenome]&&(gt[o.defaultgenome].isdefault=!0);for(const t in gt){const n=gt[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=dt(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 ${t}`).get().size)}if(n.termdbs)for(const r in n.termdbs)ft(n.termdbs[r],e.features),console.log(`${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(yt+" -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(yt+" -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]=le(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):o;if(Y(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 he(i,n,e)}catch(t){throw"Error with mds dataset "+i.label+": "+t}else ue(i,n)}ce(),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=gt[t];if(!n)throw"invalid genome name: "+t;const r=n.datasets[e];if(!r)throw"invalid dataset: "+e;st.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.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(3*e/4)].value,i=t[Math.floor(.05*e)].value,s=t[Math.floor(.95*e)].value,a=(t[Math.floor(.01*e)].value,o-r);let l,c;if(0==a)l=0,c=0;else{const n=t.findIndex((t=>t.value>r-1.5*a));l=t[-1==n?0:n].value;const i=t.findIndex((t=>t.value>o+1.5*a));c=t[-1==i?e-1:i-1].value}const u=t.filter((t=>t.value<r-1.5*a||t.value>o+1.5*a));return{w1:l,w2:c,p05:i,p25:r,p50:n,p75:o,p95:s,iqr:a,out:u}};const ie=Object.freeze([".bam",".bai",".gz",".tbi",".csi",".bw",".bb"]);function se(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]&&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 ie)if(e===u.extname(t).toLowerCase())return!0;return!1}function ae(t,e=!0){let n=null,r=!1;if(t.query.file){if(n=t.query.file,se(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 le(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 ce(){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 ue(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 "+genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+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 "+genomename+"."+t.label;const r=c.readFileSync(u.join(o.tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+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 "+genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=de(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 fe(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 de(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(yt+" -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(yt+" -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 he(t,e,n){if((t.isMds2||t.isMds3||t.isMds)&&Y(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]=le(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]=le(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=me(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=ve(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 we(o,t,e);if(n)throw r+" (vcf) error: "+n}}pe(o,t)}else{if(!o.isgenenumeric)throw"unknown type of query from "+r;{const t=_e(o);if(t)throw r+" (genenumeric) error: "+t}}}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 pe(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 me(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"},i=p.execSync(yt+" -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=ge(t.samples,e),t.hierarchySummary=ye(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(yt+" -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 ge(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 ye(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 be(t,e,n){let r;if(t.file){const[e,n]=oe(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"},i=p.execSync(yt+" -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=ge(t.samples,e),t.hierarchySummary=ye(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(yt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}console.log("("+t.type+") "+t.name+": "+(t.samples?t.samples.length:"no")+" samples, "+(t.nochr?'no 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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 ct(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 ut(t,e){for(const t of e.regions)t.lines.length>0&&t.ntwidth>=.9&&(t.to_checkmismatch=!0,t.referenceseq=await mt(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),vt(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 ft(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=dt(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=dt(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 dt(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],b=c[10];if(Number.isNaN(d)||d<=0)return;const v=d-1,_={qname:u,segstart:v,segstart_original:v,segstop:v,boxes:[],forward:!(16&f),ridx:i,seq:y,qual:b,cigarstr:h,tlen:g,flag:f,tempscore:o};if(function(t,e,n,r,o,i){const s=t.flag;if(1&s){if(64&s?t.isfirst=!0:128&s&&(t.islast=!0),"="!=e&&"*"!=e&&e!=r.chr)return t.rnext=e,void(t.pnext=n);8&s?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 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t.regions)e.to_printnt=t.stackheight>7&&e.ntwidth>=7,e.to_qual=e.ntwidth>=1;if(t.stacks.length&&(t.stackheight>=7&&n.length<2e3?t.returntemplatebox=[]:t.partstack||(t.allowpartstack=!0)),t.stackheight>=7){let e=0;for(const t of n)for(const n of t.segments)e=Math.max(e,n.x2-n.x1);e>.7*t.stackheight&&(t.canClipArrowhead=!0)}}function pt(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 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r=a.boxes.reduce(((t,e)=>t.start+t.len>e.start+e.len?t:e));if(r.start+r.len==i.boxes[0].start){t.strokeStyle=G,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(wt(t,i,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=G,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 wt(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 wt(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=L: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=L:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q,s+o.len*i.ntwidth+tt<i.width&&s<i.width&&i.x<s+tt?t.fillRect(s,n,o.len*i.ntwidth+tt,r.stackheight):s+o.len*i.ntwidth+tt<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+tt+s-i.x,r.stackheight):s+o.len*i.ntwidth+tt>=i.width&&i.x<s?t.fillRect(s,n,i.width-s,r.stackheight):s+o.len*i.ntwidth+tt>=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 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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=D(o/Q)),t.fillRect(a,n,i.ntwidth+tt,r.stackheight),a+=i.ntwidth}))}else e.discord_unmapped2&&(t.fillStyle=F),t.fillRect(s,n,o.len*i.ntwidth+tt,r.stackheight);i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial")}else{"D"==o.opr?t.strokeStyle="black":t.strokeStyle=r.stackheight<=2?U: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.len*i.ntwidth,i.x+i.width),e),t.stroke(),r.stackheight>7){const e=Math.max(i.x,s),a=Math.min(i.x+i.width,s+o.len*i.ntwidth);if(a-e>=50){const s=Math.min(10,Math.max(7,r.stackheight-2));t.font=s+"pt Arial";const l=t.measureText(o.len+" 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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(12,Math.max(7,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 xt(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(12,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/Q):t.fillStyle=z;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 kt(t,e,n){const r=yt(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]/Q)+'">'+t.seq[e.cidx+n]+"</td>");const i=[];i.push('<li><span style="background:#6B4423;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 qt(t,e,n){const r=t.boxes[0].start,o=t.boxes[t.boxes.length-1],i=o.start+o.len,s=await mt(e,n.chr+":"+(r+1)+"-"+i),a=yt(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]/Q)+'">'+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]/Q)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=20)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:#47FFFC;background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:#47FFFC;background:'+S(a[n]/Q)+'">'+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:#d48b37">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:#3B7A57;color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:#fc6df3;color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:#3B7A57;color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:#fc6df3;color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:#6B4423;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:20};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function Nt(t){const e=i.createHmac("md5",nt),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 St(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 At(r.chr,r.start,r.stop,t.get("X-Auth-Token"),t.query.gdcFileUUID,Nt(t),t.cookies.sessionid);n.push({filesize:e})}return n}async function At(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=et+"/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=Nt(e),e.query.isFileSlice=!0}if(e.query.downloadgdc)return void n.send(await St(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 it(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=dt({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}return p=[],n&&p.push(n),o&&p.push(o),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 kt(n,0,e.query)):i.push(await qt(n,t,e.query));return o.alignments&&(i[0].alignments=o.alignments),{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 it(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";if(e.query.drop_pcrduplicates&&(n.drop_pcrduplicates=!0),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[4*e],pos:Number(t[4*e+1]),ref:t[4*e+2],alt:t[4*e+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 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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(2,5*o),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(1.5*Math.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 at(t,[s]),await lt(s,t),void(t.regions[0].lines=s.lines)}await at(t,t.regions);for(const e of t.regions)await lt(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:b.type_all,regions:b.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!")}return t.sv&&t.regions.length>1?async function(t,e,n){const r=b.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[b.type_supportsv].templates.push(t);if(!e.grouptype||"support_ref"==e.grouptype)for(const t of c)r[b.type_supportref].templates.push(t);const u=[];for(const t in r){const e=r[t];0!=e.templates.length&&(t==b.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==b.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):{groups:[{type:b.type_all,regions:b.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=ft(t,e);return n=pt(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 st(n,o,t.partstack.start,t.partstack.stop,e.refseqs[0]):await st(n,o,0,0,e.refseqs[0])}else if("support_no"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await st(n,o,t.partstack.start,t.partstack.stop):await st(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 st(n,i,t.partstack.start,t.partstack.stop,e.altseqs[o]):await st(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=ft(t,r);o=pt(r,t,o),await ht(r,t,o),await ut(o,t),gt(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.canvaswidth*t.devicePixelRatio,r.canvasheight*t.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)_t(a,e,r,t);xt(a,r,0,o),t.asPaired&&(i.count.t=o.length),t.variant&&(i.diff_scores_img=await rt(t,r,o,e.max_diff_score,e.min_diff_score),"support_alt0"==i.type?i.group_color=H:"support_alt1"==i.type?i.group_color=V:"support_alt2"==i.type?i.group_color=J:"support_alt3"==i.type?i.group_color=W:"support_alt4"==i.type?i.group_color=Y:"support_alt5"==i.type?i.group_color=K:"support_ref"==i.type&&(i.group_color=X)),i.src=s.toDataURL(),e.groups.push(i),n=[...n,...o]}if(t.readcount_skipped&&(e.count.skipped=t.readcount_skipped),t.getcolorscale&&(e.colorscale=function(t){const e=160,n=20,r=100,o=p(270*t.devicePixelRatio,117*t.devicePixelRatio),i=o.getContext("2d");t.devicePixelRatio>1&&i.scale(t.devicePixelRatio,t.devicePixelRatio),i.fillStyle="black",i.font="12pt Arial",i.textAlign="center",i.fillText("Base quality",180,12);let s=29;function a(t,r,o){const s=i.createLinearGradient(100,o,260,o);s.addColorStop(0,r),s.addColorStop(1,t),i.fillStyle=s,i.fillRect(100,o,e,n)}return i.strokeStyle="black",i.beginPath(),i.moveTo(r,s),i.lineTo(r,s+4),i.moveTo(140,s),i.lineTo(140,s+4),i.moveTo(180,s),i.lineTo(180,s+4),i.moveTo(220,s),i.lineTo(220,s+4),i.moveTo(260,s),i.lineTo(260,s+4),i.closePath(),i.stroke(),i.fillText(40,r,s),i.fillText(30,140,s),i.fillText(20,180,s),i.fillText(10,220,s),i.fillText(0,260,s),i.textAlign="left",i.textBaseline="middle",s+=4,i.fillText("Match",0,s+10),a(N,q,s),s+=21,i.fillStyle="black",i.fillText("Mismatch",0,s+10),a(O,j,s),s+=21,i.fillStyle="black",i.fillText("Softclip",0,s+10),a(I,R,s),s+=21,i.fillStyle="black",i.fillText("Insertion",0,s+10),a($,z,s),{width:270,height:117,src:o.toDataURL()}}(t)),!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.canvaswidth*t.devicePixelRatio,t.pileupheight*t.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 ct(t,r),ot(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="#e0e0e0";const e=i.total*s;r.fillRect(o,t.pileupheight-e,a,e)}let l=0;if(i.A){r.fillStyle=v.A;const e=i.A*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.C){r.fillStyle=v.C;const e=i.C*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.G){r.fillStyle=v.G;const e=i.G*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.T){r.fillStyle=v.T;const e=i.T*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.softclip){r.fillStyle=R;const e=i.softclip*s;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));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)},b=new Date,v=await o("indel",JSON.stringify(y)),_=new Date;console.log("Time taken to run rust indel pipeline:",_-b,"ms");const w=v.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}}n(7147),n(334).clustalo},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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r)a.push({nt:t,v:r[t]}),i+=r[t];w.fillStyle=q;const l=S*(k-i);if(w.fillRect(N+o,l,e,S*i),a.length>1){a.sort(((t,e)=>e.v-t.v));for(let t=1;t<a.length;t++){let n=0;for(let e=0;e<t;e++)n+=a[e].v;w.fillStyle=s[a[t].nt],w.fillRect(N+o,l+S*n,e,S*a[t].v)}}w.fillStyle=q;const f=u+h+A*(d-Math.min(i,d));if(w.fillRect(N+o,f,e,A*Math.min(i,d)),a.length>1)for(let t=1;t<a.length;t++){let n=0;for(let e=0;e<t;e++)n+=a[e].v;w.fillStyle=s[a[t].nt],w.fillRect(N+o,f+A*(d-Math.min(d,i-n)),e,A*Math.min(d,a[t].v))}}N+=t.width+p}e.send({src:v.toDataURL(),allgrades:x,usegrade:c,allmax:k})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}}},2388:(t,e,n)=>{const r=n(9699),o=n(1017),i=(n(7147),n(3856)),s=n(6718).createCanvas,a=n(334);async function l(t,e,n){const o={rglst:[]};let a=0,l=0;if(t.autoscale){for(const r of t.rglst){const o=(n?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;await i.get_lines_bigfile({args:[t.file,o],dir:e,callback:t=>{const[e,n,r,o]=t.split("\t");for(const t of o.split(",")){const e=Number(t);a=Math.min(a,e),l=Math.max(l,e)}}})}o.minv=a,o.maxv=l}else a=t.minv,l=t.maxv;const c=r.makeyscale().height(t.barheight).min(a).max(l);for(const r of t.rglst){const u={chr:r.chr,start:r.start,stop:r.stop,width:r.width,reverse:r.reverse,xoff:r.xoff},f=s(r.width,t.barheight),d=f.getContext("2d"),h=(n?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;await i.get_lines_bigfile({args:[t.file,h],dir:e,callback:e=>{const[n,o,i,s]=e.split("\t"),u=Math.max(Number.parseInt(o),r.start),f=Math.min(Number.parseInt(i),r.stop),h=(r.reverse?r.stop-f:u-r.start)*r.width/(r.stop-r.start),p=(r.reverse?r.stop-u:f-r.start)*r.width/(r.stop-r.start);for(const e of s.split(",")){const n=Number(e);d.fillStyle=n>0?t.pcolor:t.ncolor;const r=c(n),o=Math.max(1,p-h);d.fillRect(h,r.y,o,2),n>l?(d.fillStyle=req.query.pcolor2,d.fillRect(h,0,o,2)):n<a&&(d.fillStyle=req.query.ncolor2,d.fillRect(h,t.barheight-2,o,2))}}}),u.img=f.toDataURL(),o.rglst.push(u)}return 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;function l(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 c(t,e,n,r,o,i){const s=i/2,a=i/2,l=Math.max(i/2,6);if(o-2*s<a)return;const c=Math.ceil((o-2*s)/(a+l));if(c<=0)return;const u="+"==e;let f=Math.ceil(n+(o-a*c-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,u,f]=r.fileurl(t);if(n)throw n;let d,h,p,m,g;if(t.query.fileIsBigbed=await o.testIfFileIsBigbed(u),t.query.getdata)t.query.getBED;else{if(d=Number(t.query.stackheight),h=Number(t.query.stackspace),p=Number(t.query.regionspace),m=Number(t.query.width),Number.isNaN(d))throw"stackheight is not integer";if(g=Math.max(10,d-2),Number.isNaN(h))throw"stackspace is not integer";if(Number.isNaN(p))throw"regionspace is not integer";if(Number.isNaN(m))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 y=t.query.color||"#3D7A4B",b=t.query.gmregion||null,v=t.query.isoform,_=t.query.onerow,w=t.query.categories||null,x=t.query.__isgene;let k;!t.query.fileIsBigbed&&f&&(k=await o.cache_index(u,t.query.indexURL));const q=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,u,k,b,v);let N;t.query.filterByName&&(N=new Set(t.query.filterByName.split(/[\s\n]/).map((t=>t.trim()))));const S=[];for(const e of q)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(N)if(n.isoform){if(!N.has(n.isoform))continue}else{if(!n.name)continue;if(!N.has(n.name))continue}S.push(n)}}if(t.query.getdata)return{items:S};if(0==S.length){const e=i(m*t.query.devicePixelRatio,d*t.query.devicePixelRatio),n=e.getContext("2d");return t.query.devicePixelRatio>1&&n.scale(t.query.devicePixelRatio,t.query.devicePixelRatio),n.font=d+"px Arial",n.fillStyle="#aaa",n.textAlign="center",n.textBaseline="middle",n.fillText("No data in view range",m/2,d/2),{src:e.toDataURL(),height:d}}const A=Math.ceil(d/4)-1;if(_||S.length>=600){const e=S.length<200,n=i(m*t.query.devicePixelRatio,d*t.query.devicePixelRatio),r=n.getContext("2d");t.query.devicePixelRatio>1&&r.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);const o=S.length<=200?[]:null;for(const n of S){const i=w&&n.category&&w[n.category]?w[n.category].color:n.color||y;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+p;const a=t.query.rglst[i.idx],u=[];n.utr5&&u.push(...n.utr5),n.utr3&&u.push(...n.utr3),!n.exon||n.coding&&0!=n.coding.length||u.push(...n.exon);for(const t of u){const e=Math.max(a.start,t[0]),i=Math.min(a.stop,t[1]),c=s+a.scale(a.reverse?i:e),u=s+a.scale(a.reverse?e:i);r.fillRect(c,A,Math.max(1,u-c),d-2*A),l(o,c,u,1,n)}const f=[];n.exon?n.coding&&n.coding.length>0&&f.push(...n.coding):f.push([n.start,n.stop]);for(const t of f){const i=Math.max(a.start,t[0]),u=Math.min(a.stop,t[1]),f=s+a.scale(a.reverse?u:i),h=s+a.scale(a.reverse?i:u);r.fillRect(f,0,Math.max(1,h-f),d),l(o,f,h,1,n),n.strand&&e&&(r.strokeStyle="white",c(r,n.strand,f,A,h-f,d-2*A))}}}return{src:n.toDataURL(),height:d,mapisoform:o}}if(t.query.hideItemNames)for(const t of S)delete t.name;let M=null;if(x&&S.length<50){M=[];for(const t of S){const e={};for(const n in t)"canvas"!=n&&"rglst"!=n&&(e[n]=t[n]);M.push(e)}}const T=t.query.rglst.reduce(((t,e)=>t+e.stop-e.start),0),C=t.query.translatecoding&&T<3*m;let j;if(C){if(!t.query.genome)throw"genome missing for translating genes";if(j=e[t.query.genome],!j)throw"invalid genome"}const O=[],E=i(10,10);let R=E.getContext("2d");t.query.devicePixelRatio>1&&R.scale(t.query.devicePixelRatio,t.query.devicePixelRatio),R.font="bold "+g+"px Arial";const I=S.length<400,P=S.length<400?[]:null;let F=!1;b&&(F=b.reverse);for(const e of t.query.rglst)e.reverse&&(F=!0);S.sort(((t,e)=>F?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 D=S.some((t=>t.exon)),L=[0];let B=1,z=null;for(const e of S){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+p;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&&C&&(e.willtranslate=!0,O.push(e));let o=n,i=r;if(I){const t=e.name;if(t){e.canvas.namestr=t;const n=R.measureText(t).width;e.canvas.namewidth=n,D?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<=m?(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>m-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(m,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<=m?(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*m&&(z=[]);for(let t=1;t<=B;t++)if(null==L[t]||L[t]<o){e.canvas.stack=t,L[t]=i;break}null==e.canvas.stack&&(B++,L[B]=i,e.canvas.stack=B),l(P,o,i,e.canvas.stack,e)}E.width=m*t.query.devicePixelRatio;const $=(d+h)*B-h;E.height=$*t.query.devicePixelRatio,R=E.getContext("2d"),t.query.devicePixelRatio>1&&R.scale(t.query.devicePixelRatio,t.query.devicePixelRatio),R.font="bold "+g+"px Arial",R.textBaseline="middle",R.lineWidth=1;for(const e of S){const n=e.canvas;if(!n)continue;const r=w&&e.category&&w[e.category]?w[e.category].color:e.color||y,o=(d+h)*(n.stack-1);R.fillStyle=r,(e.exon||e.rglst.length>1)&&(R.strokeStyle=r,R.beginPath(),R.moveTo(n.start,Math.floor(o+d/2)+.5),R.lineTo(n.stop,Math.floor(o+d/2)+.5),R.stroke());for(const i of e.rglst){let s=0;for(let e=0;e<i.idx;e++)s+=t.query.rglst[e].width+p;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 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d.push(o);for(const e of n.boxplotbysamplegroup.attributes)if(null==t[e.k])return void d.push(o);return}if(!t)return;for(const e of l.query.getgroup)if(e.kvalue!=t[e.k])return;d.push(o)}else if(n.boxplotbysamplegroup&&e.cohort&&e.cohort.annotation){if(!o.sample)return;let t;t=null==l.query.index_boxplotgroupers||0==l.query.index_boxplotgroupers?n.boxplotbysamplegroup.attributes:n.boxplotbysamplegroup.additionals[l.query.index_boxplotgroupers-1].attributes;const r=e.cohort.annotation[o.sample];if(!r)return void f.push({sample:o.sample,value:o.value});const i=r[t[0].k];if(null==i)return void f.push({sample:o.sample,value:o.value});const s=[];for(let e=1;e<t.length;e++){const n=r[t[e].k];if(null==n)break;s.push(n)}s.unshift(i);const a=s.join(", ");if(!u.has(a)){const e={samples:[],attributes:[]};for(const n of t){const t=r[n.k];if(null==t)break;const 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t.junctionAposlst)if(e==o&&r==i){const t=JSON.parse(n[5]);t.start=o,t.stop=i,a.push(t);break}}}),!r)throw"jB not found";if(0==a.length)throw"none of jA is found";const u=l(r,t,e,n);if(0==u.length)throw"no sample passing filters for junctionB";const f=new Set;u.forEach((t=>f.add(t.i)));const d=[];for(const e of a){const n=[];for(const r of e.samples)f.has(r.i)&&(t.readcountCutoff&&r.readcount<t.readcountCutoff||n.push(r));d.push({start:e.start,stop:e.stop,v:Math.floor(c(n,.5))})}return{lst:d}}(t,e,n);const r={};if(t.iscustom&&t.getsamples){const t=await o.get_header_tabix(a(n),n.dir);if(t[0]){const e=t[0].split("\t");e.length>5&&(r.sample2client=e.slice(5))}}if(!t.rglst)throw"rglst missing";if(n.viewrangeupperlimit&&t.rglst.reduce(((t,e)=>t+e.stop-e.start),0)>=n.viewrangeupperlimit)throw"zoom in under "+common.bplen(n.viewrangeupperlimit)+" to view details";let i=0,u=0;const f=[],d=new Set,h=new Set;for(const r of t.rglst)await o.get_lines_bigfile({args:[a(n),r.chr+":"+r.start+"-"+r.stop],dir:n.dir,callback:o=>{const a=o.split("\t"),p=Number.parseInt(a[1]),m=Number.parseInt(a[2]);if(n.file2){a[3];const e=a[4];let n;if("known"==e)n="canonical";else{if("novel"!=e)throw"unknown rnapeg type: "+e;n=s}if(t.infoFilter&&t.infoFilter.type&&t.infoFilter.type[n])return;const o={chr:r.chr,start:p,stop:m,info:{type:{lst:[{attrValue:n}]}}},l=[];for(let t=5;t<a.length;t++){const e=a[t];if(!e)continue;const n=Number.parseInt(e);Number.isNaN(n)||n<=0||(l.push({readcount:n}),i=Math.max(i,n))}if(0==l.length)return;if(u++,o.sampleCount=l.length,1==o.sampleCount)o.medianReadCount=l[0].readcount;else{const t=c(l,.05,.25,.5,.75,.95);o.medianReadCount=t[2],o.readcountBoxplot={percentile:t}}f.push(o)}else{if(a[3],a[4],!(p>=r.start&&p<=r.stop||m>=r.start&&m<=r.stop))return;u++;const o={chr:r.chr,start:p,stop:m,info:{type:{lst:[]}}},g=JSON.parse(a[5]);if(g.sv){o.sv=g.sv;const t=o.chr+"."+o.start+"."+o.sv.mate.chr+"."+o.sv.mate.start;if(d.has(t))return;d.add(t),d.add(o.sv.mate.chr+"."+o.sv.mate.start+"."+o.chr+"."+o.start)}if(g.canonical&&o.info.type.lst.push({attrValue:"canonical"}),g.events)for(const t in g.events){const e=g.events[t];e.__ek=t,o.info.type.lst.push(e)}else g.canonical||o.info.type.lst.push({attrValue:s});if(t.infoFilter&&t.infoFilter.type)for(const e of o.info.type.lst)if(t.infoFilter.type[e.attrValue])return;const y=l(g,t,e,n);if(0==y.length)return;if((g.exonleft||g.exonright||g.exonleftin||g.exonrightin||g.intronleft||g.intronright||g.leftout||g.rightout)&&(o.ongene={},g.exonleft&&(o.ongene.exonleft=g.exonleft),g.exonright&&(o.ongene.exonright=g.exonright),g.exonleftin&&(o.ongene.exonleftin=g.exonleftin),g.exonrightin&&(o.ongene.exonrightin=g.exonrightin),g.intronleft&&(o.ongene.intronleft=g.intronleft),g.intronright&&(o.ongene.intronright=g.intronright),g.leftout&&(o.ongene.leftout=g.leftout),g.rightout&&(o.ongene.rightout=g.rightout)),y.forEach((t=>{h.add(t.i),i=Math.max(i,t.readcount)})),o.sampleCount=y.length,1==o.sampleCount)o.medianReadCount=y[0].readcount;else{const t=c(y,.05,.25,.5,.75,.95);o.medianReadCount=t[2],o.readcountBoxplot={percentile:t}}f.push(o)}}});return r.lst=f,r.maxreadcount=i,r.junctiontotalnumber=u,h.size,r}(u,f,d);n.send(h)}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}},2728:(t,e,n)=>{"use 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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=t.cohort.db.connection.prepare("SELECT * FROM sampleidmap").all();for(const n of e)t.sampleId2Name.set(n.id,n.name),t.sampleName2Id.set(n.name,n.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){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){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){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){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 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t&&(t.token&&(e["X-Auth-Token"]=t.token),t.sessionid&&(e.Cookie="sessionid="+t.sessionid)),e}function x(t,e,n){const r=n.id.split(".");!function e(o,i){const s=r[i];if(i==r.length-1)return void(t[n.id]?t[n.id].add(o[s]):t[n.id]=o[s]);const a=o[s];if(null!=a)if(Array.isArray(a)){t[n.id]=new Set;for(const t of a)e(t,i+1)}else e(a,i+1)}(e,1),t[n.id]instanceof Set&&(t[n.id]=[...t[n.id]])}function k(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 q(t,e,n,r){if(k(e),r){if(!Array.isArray(r))throw"geneTwLst not array";t.isoforms=[];for(const e of r){var s;if(null==e||null===(s=e.term)||void 0===s||!s.name)throw"gene tw missing .term.name";if(e.term.isoform)t.isoforms.push(e.term.isoform);else{var l,u;if("object"!=typeof t.genome)throw"serverside genome obj missing, needed to map gene name to canonical isoform";if(null===(l=t.genome)||void 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f=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&f.push({term:e})}const d=e.map((t=>t.term.id));t.hiddenmclass&&(d.push("ssm.consequence.transcript.consequence_type"),d.push("ssm.consequence.transcript.transcript_id")),t.rglst&&(d.push("ssm.chromosome"),d.push("ssm.start_position"));const h={size:1e4,fields:d.join(",")};g(t,n),h.filters=F.filters(t,n);const p=w(t),m=await o.post(i.join(c,F.endpoint),{headers:p,body:JSON.stringify(h)});let y;delete t.isoforms;try{y=JSON.parse(m.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 _;if(!Array.isArray(null===(_=e.ssm)||void 0===_?void 0:_.consequence))continue;const n={};if(b(n,e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform))),t.hiddenmclass.has(n.class))continue}if(t.rglst){var q,M;if(null===(q=e.ssm)||void 0===q||!q.chromosome||null===(M=e.ssm)||void 0===M||!M.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 T,C,j,O;r.sample_id=await N(e.case,n,!0),e.case.case_id&&(r.sample_URLid=e.case.case_id,null!==(T=e.case)&&void 0!==T&&null!==(C=T.observation)&&void 0!==C&&null!==(j=C[0])&&void 0!==j&&null!==(O=j.sample)&&void 0!==O&&O.tumor_sample_uuid&&(r.sample_URLid=r.sample_URLid+"?bioId="+e.case.observation[0].sample.tumor_sample_uuid));for(const t of f)x(r,e.case,t.term);S(e.case,r),A(r,n),v.push(r)}if(r){const t={gene:r.map((t=>t.term.name)).join(","),twLst:f},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)v.push(e)}const E=new Map;for(const t of v)a([t],E,t.ssm_id);return[...E.values()]}async function N(t,e,n){var r,o,i;return n&&t.submitter_id?t.submitter_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 S(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 A(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 M(t,e,n,r){k(t);const i=[];for(const e of t)e.term&&"categorical"==e.term.type&&i.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const s=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 }}")}return`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}`}(i),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]]}});return t&&t.ssm_id_lst&&n.filters.content.push({op:"=",content:{field:"cases.gene.ssm.ssm_id",value:t.ssm_id_lst.split(",")}}),n}(e,r),l=await o.post(u,{headers:w(e),body:JSON.stringify({query:s,variables:a})});let c;try{c=JSON.parse(l.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+s+" and filter: "+filter}const f=["data","explore","cases","aggregations"];let d=c[f[0]];for(let t=1;t<f.length;t++)if(d=d[f[t]],!d)throw"."+f[t]+" missing from data structure of termid2totalsize2 for query :"+s+" and filter: "+filter;for(const t of i){if("categorical"==t.type&&!Array.isArray(d[t.path].buckets))throw f.join(".")+" not array for query :"+s+" and filter: "+filter;if(("integer"==t.type||"float"==t.type)&&"object"!=typeof d[t.path].stats)throw f.join(".")+" not object for query :"+s+" and filter: "+filter}const h=new Map;for(const t of i)if("categorical"==t.type){const e=d[t.path].buckets;let n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);h.set(t.id,n)}else if("integer"==t.type||"float"==t.type){const e=d[t.path].stats.count;h.set(t.id,{total:e})}return n?[h,n]:h}function T(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 o(c+"/ssms/"+t.ssm_id+"?fields="+e.join(","),{method:"GET",headers:w(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 C(t,e){t.queries.singleSampleMutation.get=async(t,n)=>{if(!t)throw"case_id missing";return n.case_id=t,await O(n,0,e)}}function j(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 O(e.query,0,r)})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function O(t,e,n){const s=[];{const e=await o.post(i.join(c,P.endpoint),{headers:w(t),body:JSON.stringify({size:1e3,fields:P.fields.join(","),filters:P.filters(t)})}),a=JSON.parse(e.body);for(const t of a.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 o=n.genedb.get_gene2canonicalisoform.get(e);if(!o||!o.isoform)continue;let i=t.consequence.find((t=>t.transcript.transcript_id==o.isoform));i||(i=t.consequence[0]);const a=i.transcript.aa_change||i.transcript.consequence_type,[l,c,u]=r.vepinfo(i.transcript.consequence_type);s.push({dt:r.dtsnvindel,mname:a,class:c,gene:i.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=w(t),n=await o.post(i.join(c,"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)})}),s=JSON.parse(n.body);if(!Array.isArray(s.data.hits))throw"re.data.hits[] not array";let a,l,u;for(const t of s.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){var f,d,h;const e=null===(f=t.cases)||void 0===f||null===(d=f[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;a=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;l=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;u=t.file_id}const m=[];if(l){const t=(await o(i.join(c,"data")+"/"+l,{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(a){const t=(await o(i.join(c,"data")+"/"+a,{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(u)try{const t=(await o(i.join(c,"data")+"/"+u,{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)&&(_(o,n[6]),m.push(o))}}catch(t){}return m}(t);s.push(...e)}return s}function E(t){return async(e,n)=>{try{if(!t[e.query.genome])throw"invalid genome";n.send({genes:await R({filter:e.query.filter0,CGConly:e.query.CGConly,maxGenes:e.query.maxGenes})})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function R({filter:t,CGConly:e,maxGenes:n}){if(!t)throw"filter missing";if("object"!=typeof t)throw"filter not object";const r=await o.post(i.join(c,"/analysis/top_mutated_genes_by_project"),{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:n||50,fields:"symbol",filters:I(t,e)})}),s=JSON.parse(r.body),a=[];for(const t of s.data.hits)t.symbol&&a.push(t.symbol);return a}function I(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 P={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(l(t.filterObj)),e}},F={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(l(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}}},9535:(t,e,n)=>{"use strict";n.r(e),n.d(e,{client_copy:()=>S,init:()=>N,snvindelByRangeGetter_bcf:()=>C,ssmIdFieldsSeparator:()=>x,svfusionByRangeGetter_file:()=>F,validate_termdb:()=>A});const r=n(5243),o=(n(7147),n(1017)),{initGDCdictionary:i}=n(1778),{validate_variant2samples:s}=n(817),a=n(3856),l=n(3625).compute_mclass,c=n(334),{dtsnvindel:u,dtfusionrna:f,dtsv:d,mclassfusionrna:h,mclasssv:p}=n(2273),{get_samples:m}=n(2852),{server_init_db_queries:g}=n(394),{barchart_data:y}=n(1711),{setDbRefreshRoute:b}=n(1883),v=n(2188).wz,_=n(2974).mayInitiateMatrixplots,{add_bcf_variant_filter:w}=n(3795),x=".",k="Ancestry_PC_",q="Unannotated";async function N(t,e,n,i=null,l=null){var d,h;await A(t),t.queries&&(await async function(t,e){const n=t.queries.snvindel;if(n){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)r.validate_query_snvindel_byrange(t);else if(n.byrange.bcffile){var i;n.byrange.bcffile=o.join(c.tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await C(t,e),null!==(i=n.byrange._tk)&&void 0!==i&&i.samples.length||delete n.byrange._tk.samples,T(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:o.join(c.tpmasterdir,n.byrange.chr2bcffile[t])};delete n.byrange.chr2bcffile,n.byrange.get=await C(t,e),n.byrange._tk.samples.length||delete n.byrange._tk.samples,T(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";r.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";r.validate_m2csq(t)}}}(t,e),await async function(t,e){const n=t.queries.svfusion;if(n){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=o.join(c.tpmasterdir,n.byrange.file),n.byrange.get=await F(t,e),T(t,n.byrange.samples,"svfusion.byrange")}}}(t,e),await async function(t,e){const n=t.queries.geneCnv;if(n){if(!n.bygene)throw"geneCnv.bygene missing";n.bygene.gdcapi&&r.validate_query_geneCnv(t)}}(t),await async function(t,e){const n=t.queries.ld;if(n){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.file=o.join(c.tpmasterdir,t.file),await a.validate_tabixfile(t.file),t.nochr=await a.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)if(n.gdcapi)r.validate_query_geneExpression(t);else{if(!n.file)throw".file missing from queries.geneExpression";n.file=o.join(c.tpmasterdir,n.file),await a.validate_tabixfile(n.file),n.nochr=await a.tabix_is_nochr(n.file,null,e),n.get=async e=>{let r;{const n=await E(e,null,t);n&&(r=new Set(n.map((t=>t.name))))}const o=new Map;for(const t of e.genes)o.set(t.gene,{}),await a.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)if(n.gdcapi)r.validate_query_singleSampleMutation(t,e);else{if(!n.folder)throw"unknown query method for singleSampleMutation";n.get=async e=>{var r,i,s;let l=e;if(null!==(r=t.cohort)&&void 0!==r&&null!==(i=r.termdb)&&void 0!==i&&null!==(s=i.q)&&void 0!==s&&s.sampleName2id&&(l=t.cohort.termdb.q.sampleName2id(e),null==l))return[];const u=await a.read_file(o.join(c.tpmasterdir,n.folder,l.toString()));return JSON.parse(u)}}}(t,e),s(t),function(t){if(t.ssm2canonicalisoform){if(!t.ssm2canonicalisoform.gdcapi)throw"ssm2canonicalisoform.gdcapi is false";r.validate_ssm2canonicalisoform(t.ssm2canonicalisoform)}}(t),function(t,e){e.genedb.hasTable_refseq2ensembl&&(t.refseq2ensembl_query=e.genedb.db.prepare("select ensembl from refseq2ensembl where refseq=?"))}(t,e),function(t,e){(t.queries.snvindel||t.queries.svfusion||t.queries.geneCnv)&&(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={filter0:r.filter0};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 D(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={filter0:r.filter0};if(t.queries.svfusion.byrange)return await D(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.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,mname:e.mname,_SAMPLEID_:r.sample_id,_SAMPLENAME_:r.sample_id};e.dt==u||e.dt==f||e.dt,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 i})}(t,e)),function(t){if(t.assayAvailability&&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{}";L(t,r)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";L(t,n)}}}(t),null!==(d=t.cohort)&&void 0!==d&&null!==(h=d.db)&&void 0!==h&&h.refresh&&i&&b(t,i,l)}function S(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});const r=t.queries.snvindel;if(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)),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 A(t){var e,o,s,a;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 l=t.cohort.termdb;if(null!=l&&null!==(e=l.dictionary)&&void 0!==e&&e.gdcapi)await i(t);else if(null!=l&&null!==(o=l.dictionary)&&void 0!==o&&o.dbFile)t.cohort.db={file:l.dictionary.dbFile},delete l.dictionary.dbFile,g(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";g(t)}if(l.termid2totalsize2&&(l.termid2totalsize2.gdcapi,l.termid2totalsize2.get=async(e,n={},o=null)=>l.termid2totalsize2.gdcapi?await r.get_termlst2size(e,n,o,t):await async function(t,e,n,r){const o=new Map;for(const n of t)if(n.term&&"categorical"==n.term.type){var i,s;const t={term1_id:n.id,term1_q:{type:"values"}};e.tid2value&&(t.filter=R(e.tid2value,r));const a=await y(t,r,r.cohort.termdb);if(null==a||null===(i=a.data)||void 0===i||null===(s=i.charts)||void 0===s||!s[0])continue;const l=[];for(const t of a.data.charts[0].serieses)l.push([t.seriesId,t.total]);o.set(n.id,l)}return n?[o,n]:o}(e,n,o,t)),function(t){const e=t.selectCohort;if(e){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[]"}}}(l),await async function(t){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(!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 M(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 M(o.file,e.PCcount)}}}}}(l),await v(t),await _(t),"minTimeSinceDx"in l){if(!Number.isFinite(l.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(l.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in l){if(!Number.isFinite(l.ageEndOffset))throw"termdb.ageEndOffset not number";if(l.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(l.termIds){if(l.termIds.ageDxId){const t=l.q.termjsonByOneid(l.termIds.ageDxId);if(!t)throw"unknown term for termIds.ageDxId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageDxId not integer/float"}if(l.termIds.ageLastVisitId){const t=l.q.termjsonByOneid(l.termIds.ageLastVisitId);if(!t)throw"unknown term for termIds.ageLastVisitId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageLastVisitId not integer/float"}if(l.termIds.ageNdiId){const t=l.q.termjsonByOneid(l.termIds.ageNdiId);if(!t)throw"unknown term for termIds.ageNdiId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageNdiId not integer/float"}if(l.termIds.ageDeathId){const t=l.q.termjsonByOneid(l.termIds.ageDeathId);if(!t)throw"unknown term for termIds.ageDeathId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageDeathId not integer/float"}}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(null!==(s=t.cohort)&&void 0!==s&&null!==(a=s.db)&&void 0!==a&&a.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 M(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(k+t,new Map);let r=0;for(const i of(await a.read_file(o.join(c.tpmasterdir,t))).trim().split("\n")){r++;const t=i.split("\t"),o=Number(t[0]);if(!Number.isInteger(o))throw"non-integer sample id from a line of restrictAncestries pc file";for(let r=1;r<=e;r++){const e=k+r,i=Number(t[r]);if(Number.isNaN(i))throw"non-numeric PC value from restrictAncestries file";n.get(e).set(o,i)}}return console.log(r,"samples loaded from "+t),Object.freeze(n)}function T(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 C(t,e){var n;const r=t.queries.snvindel.byrange;if(r._tk.file)await a.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 a.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=j(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 E(e,r._tk.samples,t);s&&i.push("-s",s.map((t=>t.name)).join(",")),e.variantFilter&&w(e.variantFilter,i);const c=[];return await a.get_lines_bigfile({isbcf:!0,args:i,dir:r._tk.dir,callback:t=>{const o=t.split("\t"),i=o[0],a=o[1],u=Number(o[2]),f=o[3],d=o[4].split(","),h=o[5],p={};l(r._tk,f,d,p,h,i,e.isoform);for(const t of p.mlst){var m,g;e.hiddenmclass&&e.hiddenmclass.has(t.class)||O(t,e)||(t.chr=(r._tk.nochr?"chr":"")+a,t.pos=u-1,t.ssm_id=[t.chr,t.pos,t.ref,t.alt].join(x),null!==(m=r._tk)&&void 0!==m&&null!==(g=m.samples)&&void 0!==g&&g.length&&(I(r,t,o,e.addFormatValues,0,s,n),!t.samples)||c.push(t))}}}),c}}function j(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 O(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}async function E(t,e,n){if(!e)return null;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 R(t.tid2value,e)}}(t,n);if(!r)return null;const o=[...new Set((await m(r,n)).map((t=>t.id)))],i=new Set(e.map((t=>t.name)));return o.filter((t=>i.has(t))).map((t=>({name:t})))}function R(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 I(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=[];for(const[e,o]of(i||t._tk.samples).entries()){const t=n[e+7];if(!t||"."==t)continue;const i=P(t.split(":"),a,o,r);if(i){if(s){let t=!1;for(const e in s){const n=e in i.formatK2v?i.formatK2v[e]:q;if(s[e].has(n)){t=!0;break}}if(t)continue}l.push(i)}}l.length&&(e.samples=l)}function P(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}async function F(t,e){const n=t.queries.svfusion.byrange;if(n.file)await a.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on svfusion.byrange{}";n.dir=await a.cache_index(n.url,n.indexURL)}n.nochr=await a.tabix_is_nochr(n.file||n.url,null,e);{const t=await a.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=j(e);let o;{const r=await E(e,n.samples,t);r&&(o=new Set(r.map((t=>t.name))))}const i=new Map;for(const t of e.rglst)await a.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,m,g;try{l=JSON.parse(s[3])}catch(t){return}if(l.dt!=f&&l.dt!=d)return;if(l.class=l.dt==d?p:h,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,m=l.strandA,g=[{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,m=l.strandB,g=[{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";{g=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 y=[l.dt,t.chr,a,m,c,encodeURIComponent(u)].join(x);let b;if(l.sample&&(b={sample_id:l.sample},l.mattr)){if(r)for(const t in r){const e=t in l.mattr?l.mattr[t]:q;if(r[t].has(e))return}e.addFormatValues&&(b.formatK2v=l.mattr)}i.has(y)||i.set(y,{ssm_id:y,dt:l.dt,class:l.class,chr:t.chr,pos:a,strand:m,pairlstIdx:c,mname:u,pairlst:g,samples:[]}),b&&i.get(y).samples.push(b)}});return[...i.values()]}}async function D(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 L(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:()=>s});const r=n(9699),o=(n(7147),n(1017),n(3856),n(9535).snvindelByRangeGetter_bcf),i=n(1271).run_rust;function s(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;return 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),n}(e),u=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[i,s,a]=r.fileurl({query:{file:t.bcffile,url:t.bcfurl}});if(i)throw i;const l={};a?(l.url=s,l.indexURL=t.bcfindexURL):l.file=s,n.queries.snvindel={byrange:{_tk:l}},n.queries.snvindel.byrange.get=await o(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)}if(t.filterObj&&"string"==typeof t.filterObj&&(t.filterObj=JSON.parse("string"==typeof t.filterObj&&t.filterObj.startsWith("%")?decodeURIComponent(t.filterObj):t.filterObj)),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 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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.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)}throw"insufficient query parameters for geneCnv"}(t,e);n.geneCnv=r}!function(t,e){if(e.skewer){const n=[];for(const r of e.skewer)t.rglst&&!t.rglst.find((t=>r.chr==t.chr&&r.pos>=t.start&&r.pos<=t.stop))||n.push(r);e.skewer=n}e.genecnvAtsample}(t,n),n.mclass2variantcount=function(t){const e=new Map;for(const n of t){const t=n.class||n.dt;e.set(t,1+(e.get(t)||0))}return[...e].sort(((t,e)=>e[1]-t[1]))}(n.skewer)}return function(t,e,n){const r=new Set;if(n.skewer)for(const o of n.skewer)if(o.samples){o.occurrence=o.samples.length,a(o,t),l(o,e);for(const t of o.samples)r.add(t.sample_id);delete o.samples}r.size&&(n.sampleTotalNumber=r.size)}(t,e,n),n}if(t.geneExpression){if(!e.queries.geneExpression)throw"not supported";const n=await e.queries.geneExpression.get(t);if(0==n.size)throw"no data";return 1==n.size?{gene2sample2value:n}:{clustering:await c(n)}}throw"do not know what client wants"}(s,u);n.send(f)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}}function a(t,e,n){if(e.skewerRim){if("format"!=e.skewerRim.type)throw"unknown skewerRim.type";t.rim1count=0;for(const n of t.samples){var r;(null===(r=n.formatK2v)||void 0===r?void 0:r[e.skewerRim.formatKey])==e.skewerRim.rim1value&&t.rim1count++}}}function l(t,e){var n;if(null!==(n=e.queries.snvindel)&&void 0!==n&&n.format)for(const n in e.queries.snvindel.format)if(e.queries.snvindel.format[n].isFilter){t.formatK2count||(t.formatK2count={}),t.formatK2count[n]||(t.formatK2count[n]={v2c:{},unannotatedCount:0});for(const e of t.samples){var r;const o=null===(r=e.formatK2v)||void 0===r?void 0:r[n];null==o?t.formatK2count[n].unannotatedCount++:t.formatK2count[n].v2c[o]=1+(t.formatK2count[n].v2c[o]||0)}}}async function c(t,e){const n=new Set;for(const e of t.values())for(const t in e)n.add(t);const r={matrix:[],row_names:[],col_names:[...n],plot_image:!1};for(const[e,n]of t){r.row_names.push(e);const t=[];for(const e of r.col_names)t.push(n[e]||0);r.matrix.push(t)}const o=new Date,s=await i("cluster",JSON.stringify(r)),a=new Date;let l,c,u,f;console.log("Time taken to run rust gene clustering script:",a-o,"ms");const d=s.split("\n");for(let t of d)if(t.includes("sorted_col_elements:"))l=t.replace("sorted_col_elements:","").replace("[","").replace("]","").replace(" ","").split(",").map(Number);else if(t.includes("sorted_row_elements:"))c=t.replace("sorted_row_elements:","").replace("[","").replace("]","").replace(" ","").split(",").map(Number);else if(t.includes("sorted_col_coordinates:"))f=JSON.parse(JSON.parse(t.replace("sorted_col_coordinates:","")));else if(t.includes("sorted_row_coordinates:")){u=JSON.parse(JSON.parse(t.replace("sorted_row_coordinates:","")));for(const t of u){const e=t.node_coordinates.x;t.node_coordinates.x=t.node_coordinates.y,t.node_coordinates.y=e}}else console.log(t);return{sorted_sample_elements:l,sorted_sample_coordinates:f,sorted_gene_elements:c,sorted_gene_coordinates:u,geneNameLst:r.row_names,sampleNameLst:r.col_names,matrix:r.matrix}}},4143:(t,e,n)=>{"use strict";n.d(e,{R:()=>s});const{filterJoin:r}=n(478),{get_rows_by_one_key:o}=n(2852),i=n(1271).run_rust;async function s(t,e,n,r){!function(t,e){if(!t.chr)throw"q.chr missing";if(t.start=Number(t.start),t.stop=Number(t.stop),!Number.isInteger(t.start)||!Number.isInteger(t.stop))throw"q.start/stop is not integer";if("object"!=typeof t.details)throw"q.details{} not object";if(!Array.isArray(t.details.groups))throw"q.details.groups[] not array";if(!t.details.groups[0])throw"q.details.groups[0] missing";if(t.details.groups.length>2)throw"q.details.groups[] has more than 2";for(const r of t.details.groups)if("filter"==r.type){if("object"!=typeof r.filter)throw".filter not an object for group type=filter"}else if("population"==r.type){var n;if(!r.key)throw".key missing from group type=population";if(null===(n=e.queries.snvindel)||void 0===n||!n.populations)throw"group type=population but this ds does not have 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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 e.queries.snvindel.byrange.get(n),s=l(i);return"filter"==r.type?s.totalSampleCount_group1=a(i):"filter"==(null==o?void 0:o.type)&&(s.totalSampleCount_group2=a(i)),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;"filter"!=r.type||"filter"!=i.type?"population"==r.type&&"filter"==i.type||"population"==i.type&&"filter"==r.type?await async function(t,e,n){const r=await async function(t,e,n){const r=e.groups.find((t=>"population"==t.type));if(!r)return;if(!r.adjust_race)return;const 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 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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 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=n*e.get(i).average,s.ACadj=0==s.ANadj?0:s.ACraw*s.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=200*e;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:.8em">\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>${Math.floor(o[1].refCount)}</td>\n\t\t\t\t</tr>\n\t\t\t\t</table>`}]):console.log(`${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))}n(1017),n(334)},817:(t,e,n)=>{"use strict";n.r(e),n.d(e,{combineSamplesById:()=>d,get_crosstabCombinations:()=>g,validate_variant2samples:()=>f});const{stratinput:r}=n(1881),{querySamples_gdcapi:o}=n(5243),{get_densityplot:i}=n(9402),{ssmIdFieldsSeparator:s}=n(9535),{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,y,b,v,_,w;let e=!1;if(null!==(n=t.queries)&&void 0!==n&&null!==(f=n.snvindel)&&void 0!==f&&null!==(y=f.byrange)&&void 0!==y&&null!==(b=y._tk)&&void 0!==b&&b.samples&&(e=!0),null!==(v=t.queries)&&void 0!==v&&null!==(_=v.svfusion)&&void 0!==_&&null!==(w=_.byrange)&&void 0!==w&&w.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 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b)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 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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 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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 n=await e.cohort.termdb.termid2totalsize2.get([t[0]]);for(const[t,r]of n.get(c)){const n=e.cohort.termdb.useLower?t.toLowerCase():t;l?(a.get(c).add(n),s.push({count:r,id0:c,v0:n})):a.get(c).has(n)&&s.push({count:r,id0:c,v0:n})}}const u=null==t||null===(o=t[1])||void 0===o?void 0:o.id;if(u){const n=[];for(const r of a.get(c))n.push(e.cohort.termdb.termid2totalsize2.get([t[1]],{tid2value:{[c]:r}},r));const r=await Promise.all(n);for(const[t,n]of r)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 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i=n.cohort.termdb,a={selectCohort:i.selectCohort,supportedChartTypes:i.q.getSupportedChartTypes(t.embedder),allowedTermTypes:s(n),termMatch2geneSet:i.termMatch2geneSet,massSessionDuration:r.features.massSessionDuration||30,dataDownloadCatch:i.dataDownloadCatch,matrix:i.matrix,mclass:i.mclass};i.multipleTestingCorrection&&(a.multipleTestingCorrection=i.multipleTestingCorrection),i.helpPages&&(a.helpPages=i.helpPages),i.timeScale&&(a.timeScale=i.timeScale),i.minTimeSinceDx&&(a.minTimeSinceDx=i.minTimeSinceDx),i.coxTimeMsg&&(a.coxTimeMsg=i.coxTimeMsg),i.coxStartTimeMsg&&(a.coxStartTimeMsg=i.coxStartTimeMsg),i.displaySampleIds&&(a.displaySampleIds=i.displaySampleIds),i.additionalSampleAttributes&&(a.additionalSampleAttributes=i.additionalSampleAttributes),n.assayAvailability&&(a.assayAvailability=n.assayAvailability),function(t,e){var n;const o=null===(n=r.dsCredentials)||void 0===n?void 0:n[e.dslabel];o&&(t.requiredAuth={type:o.type||"login",headerKey:o.headerKey})}(a,t),function(t,e){e.restrictAncestries&&(t.restrictAncestries=e.restrictAncestries.map((t=>({name:t.name,tvs:t.tvs}))))}(a,i),function(t,e){e.cohort.scatterplots&&(t.scatterplots=e.cohort.scatterplots.plots.map((t=>({name:t.name,dimensions:t.dimensions,colorTW:t.colorTW,shapeTW:t.shapeTW}))))}(a,n),function(t,e){e.cohort.matrixplots&&(t.matrixplots=e.cohort.matrixplots.plots.map((t=>({name:t.name}))))}(a,n),function(t,e,n){const r=e.queries;r&&(t.queries={defaultBlock2GeneMode:r.defaultBlock2GeneMode,defaultCoord:r.defaultCoord||n.defaultcoord},r.snvindel&&(t.queries.snvindel=!0))}(a,n,o),e.send({termdbConfig:a})}function s(t){var e;o(t);const n=new Set;for(const e of t.cohort.termdb.termtypeByCohort)e.type&&n.add(e.type);if(t.cohort.termdb.allowedTermTypes)for(const e of t.cohort.termdb.allowedTermTypes)n.add(e);return null!=t&&null!==(e=t.queries)&&void 0!==e&&e.snvindel&&n.add("geneVariant"),[...n]}},4453:(t,e,n)=>{"use strict";n.r(e),n.d(e,{get_incidence:()=>c,runCumincR:()=>u});const r=n(1017),o=n(2852).get_rows,i=n(3856).write_file,s=n(7147),a=n(9157),l=n(334);async function c(t,e){try{if(!e.cohort)throw"cohort missing from ds";const n=e.cohort.termdb.minTimeSinceDx;if(!n)throw"missing min time since dx";t.ds=e;const r=await o(t),i={};for(const t of r.lst){const e=t.key0,{age_dx:r,age_event:o}=JSON.parse(t.val1),s=o-r,a=s<n?n:s,l=t.key1,c=t.key2;e in i||(i[e]=[]),i[e].push({time:a,event:l,series:c})}const s={keys:["chartId","seriesId","time","cuminc","low","high","nrisk","nevent","ncensor"],case:[],refs:{bins:t.term2_id&&r.CTE2.bins?r.CTE2.bins:[]}},a={data:{},startTime:n};for(const e in i){const n=new Map;for(const t of i[e]){let e=n.get(t.series);e?(e.samplesize++,1==t.event&&e.eventcnt++,n.set(t.series,e)):(e={samplesize:1,eventcnt:1==t.event?1:0},n.set(t.series,e))}const r=new Set,o=new Set;for(const[e,i]of 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n in c[t].estimates){const r=c[t].estimates[n];for(let o=0;o<r.length;o++)e.case.push([t,n,r[o].time,r[o].est,r[o].low,r[o].up,r[o].nrisk,r[o].nevent,r[o].ncensor])}c[t].tests&&(e.tests||(e.tests={}),e.tests[t]=c[t].tests)}s.unlink(n,(()=>{}))}},5257:(t,e)=>{function n(t,e){return{CTEs:[`\n\t\t  ${e} AS (\n\t\t\t\tSELECT sample\n\t\t\t\tFROM anno_categorical\n\t\t\t\tWHERE term_id = ?\n\t\t\t\tAND value ${t.isnot?"NOT":""} IN (${t.values.map((t=>"?")).join(", ")})\n\t\t\t)`],values:[t.term.id,...t.values.map((t=>t.key))],CTEname:e}}function r(t,e){return{CTEs:[`\n\t\t  ${e} AS (\n\t\t\t\tSELECT id as sample\n\t\t\t\tFROM sampleidmap\n\t\t\t\tWHERE id IN (${Array(t.values.length).fill("?").join(", ")})\n\t\t\t)`],values:[...t.values.map((t=>t.sampleId))],CTEname:e}}async function o(t,e,n){const r={term:t.term,q:{}},o=await n.mayGetGeneVariantData(r,{genome:n.genomename}),i=[];for(const[e,n]of o){const r=n[t.term.name].values;let o=!0;for(const e of t.values){const 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p;if("tvslst"==h.type)p=await t(h,a,e);else if("categorical"==h.tvs.term.type)p=n(h.tvs,e);else if("samplelst"==h.tvs.term.type)p=r(h.tvs,e);else if("integer"==h.tvs.term.type||"float"==h.tvs.term.type)p=i(h.tvs,e,a);else if("condition"==h.tvs.term.type)p=s(h.tvs,e);else{if("geneVariant"!=h.tvs.term.type)throw"unknown term type";p=await o(h.tvs,e,a)}c.push(p.CTEname),u.push(...p.CTEs),f.push(...p.values)}const d="and"==e.join?"INTERSECT":"UNION",h=c.map((t=>"SELECT * FROM "+t)).join("\n"+d+"\n");return e.in?u.push(`\n\t\t\t\t${l} AS (\n\t\t\t\t\t${h}\n\t\t\t\t)\n\t\t\t`):u.push(`\n\t\t\t\t${l} AS (\n\t\t\t\t\tSELECT id as sample\n\t\t\t\t\tFROM sampleidmap\n\t\t\t\t\tWHERE sample NOT IN (\n\t\t\t\t\t\t${h}\n\t\t\t\t\t)\n\t\t\t\t)\n\t\t\t`),{filters:u.join(",\n"),CTEs:u,values:f,CTEname:l}}},1778:(t,e,n)=>{"use strict";n.r(e),n.d(e,{initGDCdictionary:()=>d});const r=n(6452),o=n(1017),i=n(1575).isUsableTerm,s=n(334),a=process.env.PP_GDC_HOST||"https://api.gdc.cancer.gov",l=a+(a.includes("/v0")?"":"/v0")+"/graphql",c=o.join(a,"ssm_occurrences/_mapping"),u={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}}},f={};async function d(t){const e=new Map,n=await r(c,{method:"GET",headers:{"Content-Type":"application/json",Accept:"application/json"}});let d;try{d=JSON.parse(n.body)}catch(t){throw"invalid JSON from GDC dictionary"}if(!d._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(d.fields))throw".fields not array";if(!Array.isArray(d.nested))throw".nested not array";const g=new Set(d.nested);let y=0,b=0,v=0,_=0,w=0,x=0;for(const t of d.fields){if((k=t).startsWith("ssm")||k.startsWith("case.observation")||k.startsWith("case.available_variation_data")){y++;continue}const n=t.split(".");for(let t=1;t<n.length;t++){const r=n.slice(0,t).join("."),o=r+"."+n[t],i={id:o.toLowerCase(),name:n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){i.isleaf=!0;const t=d._mapping["ssm_occurrence_centrics."+o];t&&("keyword"==t.type?(i.type="categorical",v++):"long"==t.type?(i.type="integer",i.bins=f[i.id]||JSON.parse(JSON.stringify(u)),_++):"double"==t.type&&(i.type="float",i.bins=f[i.id]||JSON.parse(JSON.stringify(u)),w++)),i.type||b++,h(i)}if(1==t);else if(i.parent_id=r,i.type){i.included_types_set.add(i.type);let t=e.get(r);for(;t&&(t.included_types_set.add(i.type),t.child_types_set.add(i.type),t.parent_id);)t=e.get(t.parent_id)}g.has(o)&&(i.isObjectList=!0),e.set(o,i)}}var k;for(const t of e.values())t.type||x++,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,",y,"lines skipped,",b,"lines with unknown term type,","categorical="+v,"integer="+_,"float="+w,"parent="+x),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,s=null,a=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const l=[];for(const n of e.values())a&&!i(n,a)||n.id.includes(t)&&l.push(JSON.parse(JSON.stringify(n)));return await r(l,s),l},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=[],v&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),_&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),w&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),await async function(t){var e,n,i;const s=await r(o.join(a,"files"),{method:"POST",headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({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})}),l=JSON.parse(s.body);if(t.gdcOpenProjects=new Set,null!=l&&null!==(e=l.data)&&void 0!==e&&null!==(n=e.aggregations)&&void 0!==n&&null!==(i=n["cases.project.project_id"])&&void 0!==i&&i.buckets){for(const e of l.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 p(a+"/ssms"),await p(a+"/ssm_occurrences"),await p(a+"/cases"),await p(a+"/files"),await p(a+"/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 r.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")}(l)}catch(t){console.error(`\n##########################################\n#\n#   GDC API unavailable\n#   ${a}\n#   ${l}\n#\n##########################################`)}}(),async function(t){try{if(t.aliquot2submitter={cache:new Map,get:async e=>t.aliquot2submitter.cache.has(e)?t.aliquot2submitter.cache.get(e):e},s.features.stopGdcCacheAliquot)return console.log("GDC aliquot2submitter not cached!");const e=await m(t,1,0);if(!Number.isInteger(e))throw"gdc totalCases not integer";const n=new Date;console.log("Start to cache aliquot IDs of",e,"cases...");const r=1e3;for(let n=0;n<Math.ceil(e/r);n++)await m(t,r,1e3*n);console.log("Done caching",t.aliquot2submitter.cache.size,"aliquot IDs.",new Date-n,"ms")}catch(t){console.log("Error at caching: "+t)}}(t)}function h(t){"case.diagnoses.age_at_diagnosis"!=t.id||(t.printDays2years=!0)}async function p(t){try{const e=new Date;await r(t),console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){throw"gdc api down: "+t}}async function m(t,e,n,o){var i,s,l;const 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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 _(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 w(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 x(t){if("condition"==t.term.type){for(const e of t.q.groupNames)if(e!=t.q.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 outcome.q.predefined_groupset_idx";const n=e.groups.find((e=>e.name!=t.refGrp));if(!n)throw"non-ref group not found for predefined-groupset";return n.name}if("custom-groupset"==t.q.type){if(!t.q.groupsetting)throw"outcome.q.groupsetting{} missing when type=predefined-groupset";if(!t.q.groupsetting.customset)throw"outcome.q.customset missing";const e=t.q.groupsetting.customset.groups.find((e=>e.name!=t.refGrp));if(!e)throw"non-ref group not found for custom-groupset";return e.name}if("values"==t.q.type){if(!t.term.values)throw"outcome.term.values{} missing";for(const e in t.term.values){const n=t.term.values[e];if(n.label!=t.refGrp)return n.label}throw"unknown nonref group from outcome.term.values"}if("custom-bin"==t.q.type){const e=t.q.lst.find((e=>e.label!=t.refGrp));if(!e)throw"non-ref bin is not found for custom-bin";return e.label}if("regular-bin"==t.q.type)throw"do not know a way to find computed bin list for type=regular-bin";throw"unknown outcome.q.type"}async function k(t,e,n,o){m=(new Date).getTime();const i=r.join(c.cachedir,Math.random().toString()+".json");await u.write_file(i,JSON.stringify(t));const f=await s(r.join(c.binpath,"utils","regression.R"),[],[i]);a.unlink(i,(()=>{})),await async function(t,e,n,r,o){if(1!=e.length)throw"expected 1 json line in R output";const i=JSON.parse(e[0]),s=i.data;y["regression.R"]=i.benchmark;for(const e of s){const i={data:{sampleSize:e.data.sampleSize,eventCnt:e.data.eventCnt?e.data.eventCnt:null}};if(e.id){const t=n[e.id];i.id=t;const o=r.independent.find((t=>"snplocus"==t.type));if(!o)throw"snplocus term missing";i.AFstr=o.snpid2AFstr.get(t),i.data.headerRow=N(t,o)}const s=e.data;if(s.residuals&&(i.data.residuals=s.residuals,i.data.residuals.label="linear"==t.regressionType?"Residuals":"Deviance residuals"),"cox"==t.regressionType){if(s.coefficients.rows.length<1)throw"fewer than 1 row in coefficients table"}else if(s.coefficients.rows.length<2)throw"fewer than 2 rows in coefficients table";i.data.coefficients={header:s.coefficients.header,intercept:"cox"==t.regressionType?null:s.coefficients.rows.shift(),terms:{},interactions:[]};for(const t of s.coefficients.rows)if(-1!=t[0].indexOf(":")){const e={},[r,o]=t.shift().split(":"),[s,a]=t.shift().split(":");e.term1=n[r],e.category1=s,e.term2=n[o],e.category2=a,e.lst=t,i.data.coefficients.interactions.push(e)}else{const e=t.shift(),r=t.shift(),o=n[e];i.data.coefficients.terms[o]||(i.data.coefficients.terms[o]={}),r?(i.data.coefficients.terms[o].categories||(i.data.coefficients.terms[o].categories={}),i.data.coefficients.terms[o].categories[r]=t):i.data.coefficients.terms[o].fields=t}i.data.coefficients.label="Coefficients",i.data.type3={header:s.type3.header,terms:{},interactions:[]},"cox"!=t.regressionType&&(i.data.type3.intercept=s.type3.rows.shift());for(const t of s.type3.rows)if(-1!=t[0].indexOf(":")){const 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 t.independent)if(e.spline&&e.spline.plotfile){i.data.splinePlots||(i.data.splinePlots=[]);const t=e.spline.plotfile,n=await a.promises.readFile(t);i.data.splinePlots.push({src:"data:image/png;base64,"+new Buffer.from(n).toString("base64"),size:l(t)}),a.unlink(t,(t=>{if(t)throw t}))}s.warnings&&(i.data.warnings=s.warnings);const c=r.independent.find((t=>"snplst"==t.type));if(c){if(c.lowAFsnps&&c.lowAFsnps.size){i.data.warnings||(i.data.warnings=[]);for(const t of c.lowAFsnps.keys())i.data.warnings.push(`${t}: effect allele frequency below cutoff, excluded from analysis`)}if(c.monomorphicLst&&c.monomorphicLst.length){i.data.warnings||(i.data.warnings=[]);for(const t of c.monomorphicLst)i.data.warnings.push(`${t}: monomorphic, excluded from analysis`)}}o.resultLst.push(i)}}(t,f,e,n,o),g=(new Date).getTime(),y.NodeJS.runRegression=(g-m)/1e3+" sec"}async function q(t,e,n,o){const i=t.independent.find((t=>"snplocus"==t.type));if(i){if(m=(new Date).getTime(),function(t,e){for(const n of t.monomorphicLst){const r=t.snpgt2count.get(n),o=[];for(const[t,e]of r)o.push(t+"="+e);const i={id:n,data:{headerRow:N(n,t)}};e.resultLst.push(i)}}(i,o),i.lowAFsnps.size)if("linear"==t.regressionType)await async function(t,e,n,o){const i={},l=new Map;for(const[r,o]of t.lowAFsnps){let t=0,s=null,a=null;const c=[],u=[];for(const{sample:r,noOutcome:i}of e){if(i)continue;const e=n.data[t++].outcome;if(!Number.isFinite(e))continue;const l=o.samples.get(r);if(!l)continue;null==s?s=a=e:(s=Math.min(s,e),a=Math.max(a,e));const[f,d]=l.split("/");f==o.effAle||d==o.effAle?c.push(e):u.push(e)}i[r]={group1values:c,group2values:u},l.set(r,{minv:s,maxv:a})}const f=r.join(c.cachedir,Math.random().toString()+".json");await u.write_file(f,JSON.stringify(i));const d=await s(r.join(c.binpath,"utils/wilcoxon.R"),[],[f]);a.unlink(f,(()=>{}));const p=JSON.parse(d);for(const e in 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d={index:i,n1:u,n2:l,n3:c,n4:t};o.push(d),i++}const a=await f("fisher",JSON.stringify({input:o}));for(const e of JSON.parse(a)){const n=s.get(e.index),{effAle:o}=t.lowAFsnps.get(n),i=e.p_value,a="chisq"===e.fisher_chisq,l={id:n,AFstr:t.snpid2AFstr.get(n),data:{headerRow:N(n,t),fisher:{isChi:a,pvalue:Number(i.toFixed(4)),rows:[["","Carry "+o+" allele","No "+o+" allele"],["Have event",e.n1,e.n3],["No event",e.n2,e.n4]]}}};r.resultLst.push(l)}}(i,e,n,o);else{if("cox"!=t.regressionType)throw"unknown regression type";await async function(t,e,n,r){const o={data:{}},i=new Set;for(const[r,s]of t.lowAFsnps){const t=[];let a=0;for(const{sample:r,noOutcome:o}of e){if(o)continue;const e=n.data[a++];if(0!==e.outcome_event&&1!==e.outcome_event)throw"d.outcome_event is not 0/1";if(!Number.isFinite(e.outcome_time))throw"d.outcome_time is not numeric";const 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={case:[],tests:{}};let a;await d(o,s);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{const t=[];for(const n of s.case)n[0]==e&&t.push(n);if(!s.tests[e]||!s.tests[e].length)throw"no tests for snp";const n=Number(s.tests[e][0].pvalue);if(!Number.isFinite(n))throw"invalid pvalue";const r={};r[e]=s.tests[e],a={pvalue:Number(n.toFixed(4)),final_data:{case:t,tests:r}}}const n={id:e,AFstr:t.snpid2AFstr.get(e),data:{headerRow:N(e,t),cuminc:a}};r.resultLst.push(n)}}(i,e,n,o)}g=(new Date).getTime(),y.NodeJS.snplocusPostprocess=(g-m)/1e3+" sec"}}function N(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("&nbsp;&nbsp;&nbsp;")}}function S(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 A(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 o=n[t+c.cache_snpgt.sampleColumn];o&&a.get(r).samples.set(e,o)}}"snplocus"!=t.type&&function(t,e,n,r){if(0!=e.q.missingGenotype){if(1==e.q.missingGenotype)throw"not done";if(2!=e.q.missingGenotype)throw"invalid missingGenotype value";{const e=new Set;for(const{samples:o}of t.values())for(const[t,i]of n.entries())r[t]&&(o.has(i)||e.add(i));for(const{samples:n}of t.values())for(const t of e)n.delete(t)}}else for(const e of t.values()){let t;if(e.refAle!=e.effAle)t=e.refAle;else for(const n of e.altAles)if(n!=e.effAle){t=n;break}if(!t)throw"not finding a non-effect allele";for(const[o,i]of n.entries())r[o]&&(e.samples.has(i)||e.samples.set(i,t+"/"+t))}}(a,t,i,s),t.snpgt2count=new Map;for(const[e,n]of a){const r=new Map;for(const[t,e]of n.samples)r.set(e,1+(r.get(e)||0));t.snpgt2count.set(e,r)}!function(t,e){t.lowAFsnps=new Map,t.highAFsnps=new Map,t.monomorphicLst=[],t.snpid2AFstr=new Map;for(const[n,r]of e){if(1==t.snpgt2count.get(n).size){t.monomorphicLst.push(n);continue}const e=r.samples.size;let o=0;for(const[t,e]of r.samples){const[t,n]=e.split("/");o+=(t==r.effAle?1:0)+(n==r.effAle?1:0)}const i=o/(2*e);t.snpid2AFstr.set(n,(100*i).toFixed(1)+"%"),i<t.q.AFcutoff/100?t.lowAFsnps.set(n,r):t.highAFsnps.set(n,r)}}(t,a);for(const[n,r]of t.highAFsnps)for(const[o,i]of r.samples){const[s,a]=i.split("/"),l=M(t,r.effAle,s,a);e.get(o).id2value.set(n,{key:l,value:l})}}function M(t,e,n,r){switch(t.q.geneticModel){case 0:return(n==e?1:0)+(r==e?1:0);case 1:return n==e||r==e?1:0;case 2:return n==e&&r==e?1:0;case 3:return n+"/"+r;default:throw"unknown geneticModel option"}}function T(t,e){if(t.tag===e)return t;if("tvslst"===t.type)for(const n of t.lst){const t=T(n,e);if(t)return t}}},2188:(t,e,n)=>{"use strict";n.d(e,{uR:()=>m,wz:()=>p});var r=n(2974),o=n(1017),i=n.n(o),s=n(3856),a=n(334),l=n.n(a),c=n(2273),u=n(2852),f=n(5257),d=n(6191),h=n.n(d);async function p(t){if(t.cohort.scatterplots){if(!Array.isArray(t.cohort.scatterplots.plots))throw"cohort.scatterplots.plots is 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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;c.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;c.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;c.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 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0!==a&&a.draftChartTypes&&i[n.cohort].add(...r.features.draftChartTypes),"survival"!=n.type||i[n.cohort].has("survival")||i[n.cohort].add("survival"),"condition"!=n.type||i[n.cohort].has("cuminc")||i[n.cohort].add("cuminc"),"float"!=n.type&&"integer"!=n.type||(s[n.cohort]+=n.samplecount)}for(const t in i)i[t]=[...i[t]];if(t.cohort.allowedChartTypes)for(const e in i)i[e]=i[e].filter((e=>t.cohort.allowedChartTypes.includes(e)));if(t.queries){if(t.queries.snvindel||t.queries.trackLst)for(const t in i)i[t].push("genomeBrowser");if(t.queries.geneExpression)for(const t in i)i[t].push("geneExpression")}return i}}function a(t){const e=t.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(e.map((t=>t.name)))}function l(t){var e,n;if(t.cohort.termdb.termtypeByCohort){if(!Array.isArray(t.cohort.termdb.termtypeByCohort))throw"termtypeByCohort is not array"}else{if(null===(e=t.cohort)||void 0===e||null===(n=e.db)||void 0===n||!n.connection)throw"termtypeByCohort[] not 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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,c=[];for(const t of e){if(t.invalid)continue;let e;var u;if(s.chr2files){if(e=null===(u=s.chr2files)||void 0===u?void 0:u[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);c.push(n)}const f=o.join(a.cachedir,await i.write_tmpfile(c.join("\n"))),d=o.join(a.cachedir,await i.write_tmpfile([...l].join("\n")));await i.get_lines_bigfile({isbcf:!0,args:["query","-R",f,"-f","%CHROM\t%POS\t%REF\t%ALT[\t%TGT]\n","-v",d],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]?"":n[t])}}}),r.unlink(f,(()=>{})),r.unlink(d,(()=>{}));const h=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid||t.gtlst&&(h.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele||"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const p=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random());return await i.write_file(o.join(a.cache_snpgt.dir,p),h.join("\n")),p}(t,s,e);return{snps:s,cacheid:l}}(t,n,c);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,f;if(e.track){if(c=e.track.vcf,!c)throw"ds.track.vcf missing";if(f=c.chr2bcffile[t.chr],!f)throw"chr not in chr2bcffile"}else{var d;if(c=e.queries.snvindel.byrange._tk,f=c.chr2files?null===(d=c.chr2files)||void 0===d?void 0:d[t.chr].file:c.file||c.url,!f)throw"no bcf file"}const h=["query",f,"-r",(c.nochr?t.chr.replace("chr",""):t.chr)+":"+r+"-"+s,"-f","%POS\t%ID\t%REF\t%ALT\t%INFO[\t%TGT]\n"];t.variant_filter&&u(t.variant_filter,h);const p={snps:[]},m=["snpid\tchr\tpos\tref\talt\teff\t"+c.samples.map((t=>t.name)).join("\t")];return await i.get_lines_bigfile({isbcf:!0,args:h,dir:c.dir,callback:(e,n)=>{if(p.snps.length>=1e3)return n.kill(),void(p.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]),p.snps.push(u);const f=[a,t.chr,o,i,s.join(","),""];for(let t=5;t<r.length;t++)f.push("."==r[t]?"":r[t]);m.push(f.join("\t"))}}),p.cacheid=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random()),await i.write_file(o.join(a.cache_snpgt.dir,p.cacheid),m.join("\n")),p}(t,n);throw"unknown how to validate"}catch(t){return t.stack&&console.log(t.stack),{error:t.message||t}}}function u(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 anno_categorical\n\t\t\t\tWHERE term_id=? ${s.clause}\n\t\t\t)`,tablename:t}}};let i=0;const s={async getCTE(t,e,n,r,o,s){if(!s.groups)throw`.groups[] missing from a group-set, term.id='${e.id}'`;const a=[],l=[];for(const t of s.groups)if("values"==t.type)a.push(`SELECT sample, ? as key, value\n\t\t\t\t\tFROM anno_categorical a\n\t\t\t\t\tWHERE term_id=?\n\t\t\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t\t\t`),o.push(t.name,e.id,...t.values.map((t=>t.key.toString())));else{if("filter"!=t.type)throw`unsupported groupset type='${t.type}'`;if(!("activeCohort"in r.groupsetting)||!t.filter4activeCohort)throw`activeCohort error: cannot construct filter statement for group name='${t.name}', term.id=${e.id}`;{const s=t.filter4activeCohort[r.groupsetting.activeCohort],c=await getFilterCTEs(s,n,"xf"+i++);if(!c)throw`unable to construct a group='${t.name}' filter for term.id='${e.id}'`;l.push(c.filters),o.push(...c.values.slice(),t.name,t.name),a.push(`SELECT sample, ? AS key, ? AS value\n\t\t\t\t\t\tFROM ${c.CTEname}`)}}return{sql:`${l.length?l.join("\n,")+",":""}\n\t\t\t${t} AS (\n\t\t\t\t${a.join("\nUNION ALL\n")}\n\t\t\t)`,tablename:t}}}},6759:(t,e,n)=>{"use strict";function r(t){const e=t.cohort.db.connection.prepare("select * from features").all();return{cohorts:t.cohort.db.connection.prepare("select * from cohorts where cohort in (select distinct(cohort) from cohort_features)\n\t\t order by sample_count desc").all(),features:e,cfeatures:t.cohort.db.connection.prepare("select * from cohort_features").all()}}n.r(e),n.d(e,{getCohortsData:()=>r})},9723:(t,e,n)=>{"use strict";n.r(e),n.d(e,{binary:()=>i,discrete:()=>o,time2event:()=>s});var r=n(2852);const o={getCTE(t,e,n,o,i){if(o.breaks&&o.breaks.length>0)return l(t,e,o,i);{const[n,s]=a(o);i.push(e.id,n);const l=(0,r.getUncomputableClause)(e,o);return i.push(...l.values),{sql:`${t} AS (\n\t\t\t\t\tSELECT\n\t\t\t\t\t\tsample,\n\t\t\t\t\t\t${"grade"==n?"CAST(value AS integer) as key":"value as key"},\n\t\t\t\t\t\t${"grade"==n?"CAST(value AS integer) as value":"value"}\n\t\t\t\t\tFROM\n\t\t\t\t\t\tprecomputed\n\t\t\t\t\tWHERE\n\t\t\t\t\t\tterm_id = ?\n\t\t\t\t\t\tAND value_for = ?\n\t\t\t\t\t\tAND ${s} = 1\n\t\t\t\t\t\t${l.clause}\n\t\t\t\t)`,tablename:t}}}},i={getCTE(t,e,n,r,o){if(!r.breaks)throw"binary mode requires breaks";if(1!=r.breaks.length)throw"binary mode requires one break";return l(t,e,r,o)}},s={getCTE(t,e,n,r,o){if(!r.breaks||1!=r.breaks.length)throw"one break is required";const{ageDxId:i,ageLastVisitId:s,ageNdiId:a,ageDeathId:l}=n.cohort.termdb.termIds;if(!(i&&s&&a&&l))throw"missing age terms ids";const c=`ageDx AS (\n\t\t\tSELECT sample, ROUND(value,2) AS value\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(i).type}\n\t\t\tWHERE term_id = ?\n\t\t)`;o.push(i);const u=`ageLastVisit AS (\n\t\t\tSELECT sample, ROUND(value,2) AS value\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(s).type}\n\t\t\tWHERE term_id = ?\n\t\t)`;o.push(s);const f=`ageNdi AS (\n\t\t\tSELECT sample, ROUND(value,2) AS value\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(a).type}\n\t\t\tWHERE term_id = ?\n\t\t)`;o.push(a);const d=`dead AS (\n\t\t\tSELECT anno.sample, ageDx.value AS ageDx, ageNdi.value AS ageNdi, ROUND(anno.value,2) AS ageDeath\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(l).type} anno\n\t\t\tJOIN ageNdi ON anno.sample = ageNdi.sample\n\t\t\tJOIN ageDx ON anno.sample = ageDx.sample\n\t\t\tWHERE anno.term_id = ?\n\t\t)`;let h;return o.push(l),h=e.isleaf?"eventTerms AS (\n\t\t\t\tSELECT term_id\n\t\t\t\tFROM chronicevents\n\t\t\t\tWHERE term_id = ?\n\t\t\t)":"parentTerms AS (\n\t\t\t\t\tSELECT distinct(ancestor_id) \n\t\t\t\t\tFROM ancestry\n\t\t\t\t),\n\t\t\t\teventTerms AS (\n\t\t\t\t\tSELECT a.term_id \n\t\t\t\t\tFROM ancestry a\n\t\t\t\t\tJOIN terms t ON t.id = a.term_id AND t.id NOT IN parentTerms \n\t\t\t\t\tWHERE a.ancestor_id = ?\n\t\t\t\t)",o.push(e.id),o.push(r.breaks[0]),{sql:`${c},\n\t\t\t${u},\n\t\t\t${f},\n\t\t\t${d},\n\t\t\ttimeToEvent AS (\n\t\t\tSELECT c.*, ageDx.value AS ageDx, ageLastVisit.value AS ageLastVisit, ageNdi.value AS ageNdi\n\t\t\tFROM chronicevents c\n\t\t\tJOIN ageDx ON c.sample = ageDx.sample\n\t\t\tJOIN ageLastVisit ON c.sample = ageLastVisit.sample\n\t\t\tJOIN ageNdi ON c.sample = ageNdi.sample\n\t\t\tWHERE c.years_to_event > 0\n\t\t\tAND c.grade <= 5\n\t\t),\n\t\t\t${h},\n\t\t\tevent1 AS (\n\t\t\tSELECT sample, 1 AS key, json_object('age_dx', ageDx, 'age_event', MIN(age_graded)) AS value\n\t\t\tFROM timeToEvent\n\t\t\tWHERE term_id IN eventTerms\n\t\t\tAND (\n\t\t\t\t(grade >= ? AND age_graded <= ageLastVisit)\n\t\t\t\tOR\n\t\t\t\t(grade = 5 AND age_graded <= ageNdi)\n\t\t\t)\n\t\t\tGROUP BY sample\n\t\t),\n\t\t\tevent1samples AS (\n\t\t\tSELECT sample\n\t\t\tFROM event1\n\t\t),\n\t\t\tevent2 AS (\n\t\t\tSELECT sample, 2 AS key, json_object('age_dx', ageDx, 'age_event', ageDeath) AS value\n\t\t\tFROM dead\n\t\t\tWHERE ageDeath <= ageNdi\n\t\t\tAND sample NOT IN event1samples\n\t\t),\n\t\t\tevent2samples AS (\n\t\t\tSELECT sample\n\t\t\tFROM event2\n\t\t),\n\t\t\tevent0 AS (\n\t\t\tSELECT DISTINCT sample, 0 AS key, json_object('age_dx', ageDx, 'age_event', ageLastVisit) AS value\n\t\t\tFROM timeToEvent\n\t\t\tWHERE sample NOT IN event1samples\n\t\t\tAND sample NOT IN event2samples\n\t\t),\n\t\t\t${t} AS (\n\t\t\t\tSELECT * FROM event1\n\t\t\t\tUNION ALL\n\t\t\t\tSELECT * FROM event2\n\t\t\t\tUNION ALL\n\t\t\t\tSELECT * FROM event0\n\t\t\t)`,tablename:t}}};function a(t){const e=t.bar_by_children?"child":t.bar_by_grade?"grade":"";if(!e)throw"must set the bar_by_grade or bar_by_children query parameter";const n=t.value_by_max_grade?"max_grade":t.value_by_most_recent?"most_recent":t.value_by_computable_grade?"computable_grade":"";if(!n)throw"must set a valid value_by_*";return[e,n]}function l(t,e,n,r){const o=n.breaks,i=Object.keys(e.values).map(Number).sort(((t,e)=>t-e)),s=[];let l,c={values:[]};for(const t of i)o.includes(t)?(l=t,0===s.length?c.name="Grade < "+l:c.name=c.name+" < "+l,s.push(c),c={name:l+" =< Grade",values:[t]}):c.values.push(t);if(c.name="Grade >= "+l,s.push(c),n.groupNames&&n.groupNames.length>0)for(const[t,e]of n.groupNames.entries())s[t].name=e;const[u,f]=a(n),d=[];for(const t of s)d.push(`SELECT sample, ? as key, value\n\t\t\tFROM precomputed a\n\t\t\tWHERE\n\t\t\t\tterm_id=?\n\t\t\t\tAND value_for=?\n\t\t\t\tAND ${f}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,u,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${d.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:()=>m,get_rows_by_one_key:()=>p,get_samplecount:()=>f,get_samples:()=>u,get_summary:()=>y,get_summary_conditioncategories:()=>h,get_summary_numericcategories:()=>d,get_term_cte:()=>g,interpolateSqlValues:()=>k});const r=n(9699),o=n(3594),i=n(5257).getFilterCTEs,s=n(827),a=n(2747),l=n(9723),c=n(610).s;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 (${o.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(s).all(r)}async function h(t){let e;if(t.term1_q&&"cox"==t.term1_q.mode){e=await m(t,{withCTEs:!0});const n=t.ds.cohort.termdb.minTimeSinceDx;if(!n)throw"missing min time since dx";const r=new Map;for(const t of e.lst){let e;e=2===t.key1?0:t.key1;const{age_dx:o,age_event:i}=JSON.parse(t.val1);i-(o+n)<0&&(e=-1);const s=r.get(e);s?r.set(e,s+1):r.set(e,1)}const o=[];for(const[t,e]of r)o.push({key1:t,samplecount:e});e.lst=o}else e=await m(t,{withCTEs:!0,groupby:"key1"});const n=[0,1,2],r={};for(const o of n)r[o]=b(t,o,e);for(const t of e.lst)for(const e of n)r[e](t);return e}async function p(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await i(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const o=`\n\t\t${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 m(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 g(t,o,0,r),a=await g(t,o,1,r),l=await g(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 g(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 found 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one could be a survival term";if("survival"!=t.term2.type&&"survival"!=t.term1.type)throw"no survival terms, either the main term OR the overlay term must be a survival term"}else if("survival"!=t.term1.type)throw"non-survival term";if(t.term0&&"survival"==t.term0.type)throw"term0 must not be a survival term";const f=function(t){if(t.term1&&"survival"==t.term1.type)return 1;if(!t.term2)throw"term1.type is not survival and term2 is missing";if("survival"!=t.term2.type)throw"both term1 and term2 are not survival type";return 2}(t),d=t[`term${f}`],h=t["term"+(1==f?2:1)],p=await o({terms:c,filter:t.filter},e,t.genome);if(p.error)throw p.error;const m=function(t,e){return Object.values(t.samples).filter((t=>t[e.id])).sort(((t,n)=>t[e.id].value<n[e.id].value?-1:1))}(p,d),g={},y={chart:new Set,series:new Set};for(const e of m){const n=e[d.id],r=n.value;if(r<0)continue;const o=n.key;let i;if(h)if("id"in h){if(!(h.id in e))continue;i=e[h.id].key}else if("samplelst"==h.type){if(!(h.name in 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Array(3).concat("ef8a62f7f7f767a9cf","ca0020f4a58292c5de0571b0","ca0020f4a582f7f7f792c5de0571b0","b2182bef8a62fddbc7d1e5f067a9cf2166ac","b2182bef8a62fddbc7f7f7f7d1e5f067a9cf2166ac","b2182bd6604df4a582fddbc7d1e5f092c5de4393c32166ac","b2182bd6604df4a582fddbc7f7f7f7d1e5f092c5de4393c32166ac","67001fb2182bd6604df4a582fddbc7d1e5f092c5de4393c32166ac053061","67001fb2182bd6604df4a582fddbc7f7f7f7d1e5f092c5de4393c32166ac053061").map(r);const N=m(q);var S=new Array(3).concat("ef8a62ffffff999999","ca0020f4a582bababa404040","ca0020f4a582ffffffbababa404040","b2182bef8a62fddbc7e0e0e09999994d4d4d","b2182bef8a62fddbc7ffffffe0e0e09999994d4d4d","b2182bd6604df4a582fddbc7e0e0e0bababa8787874d4d4d","b2182bd6604df4a582fddbc7ffffffe0e0e0bababa8787874d4d4d","67001fb2182bd6604df4a582fddbc7e0e0e0bababa8787874d4d4d1a1a1a","67001fb2182bd6604df4a582fddbc7ffffffe0e0e0bababa8787874d4d4d1a1a1a").map(r);const A=m(S);var M=new Array(3).concat("fc8d59ffffbf91bfdb","d7191cfdae61abd9e92c7bb6","d7191cfdae61ffffbfabd9e92c7bb6","d73027fc8d59fee090e0f3f891bfdb4575b4","d73027fc8d59fee090ffffbfe0f3f891bfdb4575b4","d73027f46d43fdae61fee090e0f3f8abd9e974add14575b4","d73027f46d43fdae61fee090ffffbfe0f3f8abd9e974add14575b4","a50026d73027f46d43fdae61fee090e0f3f8abd9e974add14575b4313695","a50026d73027f46d43fdae61fee090ffffbfe0f3f8abd9e974add14575b4313695").map(r);const T=m(M);var C=new Array(3).concat("fc8d59ffffbf91cf60","d7191cfdae61a6d96a1a9641","d7191cfdae61ffffbfa6d96a1a9641","d73027fc8d59fee08bd9ef8b91cf601a9850","d73027fc8d59fee08bffffbfd9ef8b91cf601a9850","d73027f46d43fdae61fee08bd9ef8ba6d96a66bd631a9850","d73027f46d43fdae61fee08bffffbfd9ef8ba6d96a66bd631a9850","a50026d73027f46d43fdae61fee08bd9ef8ba6d96a66bd631a9850006837","a50026d73027f46d43fdae61fee08bffffbfd9ef8ba6d96a66bd631a9850006837").map(r);const j=m(C);var O=new Array(3).concat("fc8d59ffffbf99d594","d7191cfdae61abdda42b83ba","d7191cfdae61ffffbfabdda42b83ba","d53e4ffc8d59fee08be6f59899d5943288bd","d53e4ffc8d59fee08bffffbfe6f59899d5943288bd","d53e4ff46d43fdae61fee08be6f598abdda466c2a53288bd","d53e4ff46d43fdae61fee08bffffbfe6f598abdda466c2a53288bd","9e0142d53e4ff46d43fdae61fee08be6f598abdda466c2a53288bd5e4fa2","9e0142d53e4ff46d43fdae61fee08bffffbfe6f598abdda466c2a53288bd5e4fa2").map(r);const E=m(O);var R=new Array(3).concat("e5f5f999d8c92ca25f","edf8fbb2e2e266c2a4238b45","edf8fbb2e2e266c2a42ca25f006d2c","edf8fbccece699d8c966c2a42ca25f006d2c","edf8fbccece699d8c966c2a441ae76238b45005824","f7fcfde5f5f9ccece699d8c966c2a441ae76238b45005824","f7fcfde5f5f9ccece699d8c966c2a441ae76238b45006d2c00441b").map(r);const I=m(R);var P=new Array(3).concat("e0ecf49ebcda8856a7","edf8fbb3cde38c96c688419d","edf8fbb3cde38c96c68856a7810f7c","edf8fbbfd3e69ebcda8c96c68856a7810f7c","edf8fbbfd3e69ebcda8c96c68c6bb188419d6e016b","f7fcfde0ecf4bfd3e69ebcda8c96c68c6bb188419d6e016b","f7fcfde0ecf4bfd3e69ebcda8c96c68c6bb188419d810f7c4d004b").map(r);const F=m(P);var D=new Array(3).concat("e0f3dba8ddb543a2ca","f0f9e8bae4bc7bccc42b8cbe","f0f9e8bae4bc7bccc443a2ca0868ac","f0f9e8ccebc5a8ddb57bccc443a2ca0868ac","f0f9e8ccebc5a8ddb57bccc44eb3d32b8cbe08589e","f7fcf0e0f3dbccebc5a8ddb57bccc44eb3d32b8cbe08589e","f7fcf0e0f3dbccebc5a8ddb57bccc44eb3d32b8cbe0868ac084081").map(r);const L=m(D);var B=new Array(3).concat("fee8c8fdbb84e34a33","fef0d9fdcc8afc8d59d7301f","fef0d9fdcc8afc8d59e34a33b30000","fef0d9fdd49efdbb84fc8d59e34a33b30000","fef0d9fdd49efdbb84fc8d59ef6548d7301f990000","fff7ecfee8c8fdd49efdbb84fc8d59ef6548d7301f990000","fff7ecfee8c8fdd49efdbb84fc8d59ef6548d7301fb300007f0000").map(r);const z=m(B);var $=new Array(3).concat("ece2f0a6bddb1c9099","f6eff7bdc9e167a9cf02818a","f6eff7bdc9e167a9cf1c9099016c59","f6eff7d0d1e6a6bddb67a9cf1c9099016c59","f6eff7d0d1e6a6bddb67a9cf3690c002818a016450","fff7fbece2f0d0d1e6a6bddb67a9cf3690c002818a016450","fff7fbece2f0d0d1e6a6bddb67a9cf3690c002818a016c59014636").map(r);const Z=m($);var U=new Array(3).concat("ece7f2a6bddb2b8cbe","f1eef6bdc9e174a9cf0570b0","f1eef6bdc9e174a9cf2b8cbe045a8d","f1eef6d0d1e6a6bddb74a9cf2b8cbe045a8d","f1eef6d0d1e6a6bddb74a9cf3690c00570b0034e7b","fff7fbece7f2d0d1e6a6bddb74a9cf3690c00570b0034e7b","fff7fbece7f2d0d1e6a6bddb74a9cf3690c00570b0045a8d023858").map(r);const G=m(U);var H=new Array(3).concat("e7e1efc994c7dd1c77","f1eef6d7b5d8df65b0ce1256","f1eef6d7b5d8df65b0dd1c77980043","f1eef6d4b9dac994c7df65b0dd1c77980043","f1eef6d4b9dac994c7df65b0e7298ace125691003f","f7f4f9e7e1efd4b9dac994c7df65b0e7298ace125691003f","f7f4f9e7e1efd4b9dac994c7df65b0e7298ace125698004367001f").map(r);const V=m(H);var J=new Array(3).concat("fde0ddfa9fb5c51b8a","feebe2fbb4b9f768a1ae017e","feebe2fbb4b9f768a1c51b8a7a0177","feebe2fcc5c0fa9fb5f768a1c51b8a7a0177","feebe2fcc5c0fa9fb5f768a1dd3497ae017e7a0177","fff7f3fde0ddfcc5c0fa9fb5f768a1dd3497ae017e7a0177","fff7f3fde0ddfcc5c0fa9fb5f768a1dd3497ae017e7a017749006a").map(r);const W=m(J);var Y=new Array(3).concat("edf8b17fcdbb2c7fb8","ffffcca1dab441b6c4225ea8","ffffcca1dab441b6c42c7fb8253494","ffffccc7e9b47fcdbb41b6c42c7fb8253494","ffffccc7e9b47fcdbb41b6c41d91c0225ea80c2c84","ffffd9edf8b1c7e9b47fcdbb41b6c41d91c0225ea80c2c84","ffffd9edf8b1c7e9b47fcdbb41b6c41d91c0225ea8253494081d58").map(r);const K=m(Y);var X=new Array(3).concat("f7fcb9addd8e31a354","ffffccc2e69978c679238443","ffffccc2e69978c67931a354006837","ffffccd9f0a3addd8e78c67931a354006837","ffffccd9f0a3addd8e78c67941ab5d238443005a32","ffffe5f7fcb9d9f0a3addd8e78c67941ab5d238443005a32","ffffe5f7fcb9d9f0a3addd8e78c67941ab5d238443006837004529").map(r);const Q=m(X);var tt=new 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Array(3).concat("e5f5e0a1d99b31a354","edf8e9bae4b374c476238b45","edf8e9bae4b374c47631a354006d2c","edf8e9c7e9c0a1d99b74c47631a354006d2c","edf8e9c7e9c0a1d99b74c47641ab5d238b45005a32","f7fcf5e5f5e0c7e9c0a1d99b74c47641ab5d238b45005a32","f7fcf5e5f5e0c7e9c0a1d99b74c47641ab5d238b45006d2c00441b").map(r);const at=m(st);var lt=new Array(3).concat("f0f0f0bdbdbd636363","f7f7f7cccccc969696525252","f7f7f7cccccc969696636363252525","f7f7f7d9d9d9bdbdbd969696636363252525","f7f7f7d9d9d9bdbdbd969696737373525252252525","fffffff0f0f0d9d9d9bdbdbd969696737373525252252525","fffffff0f0f0d9d9d9bdbdbd969696737373525252252525000000").map(r);const ct=m(lt);var ut=new Array(3).concat("efedf5bcbddc756bb1","f2f0f7cbc9e29e9ac86a51a3","f2f0f7cbc9e29e9ac8756bb154278f","f2f0f7dadaebbcbddc9e9ac8756bb154278f","f2f0f7dadaebbcbddc9e9ac8807dba6a51a34a1486","fcfbfdefedf5dadaebbcbddc9e9ac8807dba6a51a34a1486","fcfbfdefedf5dadaebbcbddc9e9ac8807dba6a51a354278f3f007d").map(r);const ft=m(ut);var dt=new 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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;no(t,o,i)}t[n+1]=t[i],t[i]=s,r-o+1>=i-n?(eo(t,e,o,r),eo(t,e,n,i-1)):(eo(t,e,n,i-1),eo(t,e,o,r))}}function no(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function ro(t){return t[0]}function oo(t){return t[1]}const io=1e-6;class so{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)>io||Math.abs(this._y1-o)>io)&&(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 ao{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 lo{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(2*t.points.length),this.vectors=new Float64Array(2*t.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/3*2);for(let e,r,i=0,s=0,a=n.length;i<a;i+=3,s+=2){const a=2*n[i],l=2*n[i+1],c=2*n[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,b=p-u,v=m-f,_=2*(g*v-y*b);if(Math.abs(_)<1e-9){let o=1e9;const i=2*n[0];o*=Math.sign((t[i]-u)*v-(t[i+1]-f)*b),e=(u+p)/2-o*v,r=(f+m)/2+o*b}else{const t=1/_,n=g*g+y*y,o=b*b+v*v;e=u+(v*n-y*o)*t,r=f+(g*o-b*n)*t}o[s]=e,o[s+1]=r}let i,s,a,l=e[e.length-1],c=4*l,u=t[2*l],f=t[2*l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],i=c,s=u,a=f,c=4*l,u=t[2*l],f=t[2*l+1],r[i+2]=r[c]=a-f,r[i+3]=r[c+1]=u-s}render(t){const e=null==t?t=new so: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=2*Math.floor(e/3),s=2*Math.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=2*Math.floor(r[l]/3),c=i[n],u=i[n+1],f=4*a,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 so: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 so: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 ao;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[2*n],e[2*n+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=4*t;return n[r]||n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,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 co=2*Math.PI,uo=Math.pow;function fo(t){return t[0]}function ho(t){return t[1]}function po(t,e,n){return[t+Math.sin(t+e)*n,e+Math.cos(t-e)*n]}class mo{static from(t,e=fo,n=ho,r){return new mo("length"in t?function(t,e,n,r){const o=t.length,i=new Float64Array(2*o);for(let s=0;s<o;++s){const o=t[s];i[2*s]=e.call(r,o,s,t),i[2*s+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=2*e[t],o=2*e[t+1],i=2*e[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[2*t]-e[2*n]||e[2*t+1]-e[2*n+1]));const t=this.collinear[0],n=this.collinear[this.collinear.length-1],r=[e[2*t],e[2*t+1],e[2*n],e[2*n+1]],o=1e-8*Math.hypot(r[3]-r[1],r[2]-r[0]);for(let t=0,n=e.length/2;t<n;++t){const n=po(e[2*t],e[2*t+1],o);e[2*t]=n[0],e[2*t+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 lo(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=uo(e-l[2*t],2)+uo(n-l[2*t+1],2);const f=r[t];let d=f;do{let r=a[d];const f=uo(e-l[2*r],2)+uo(n-l[2*r+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&&uo(e-l[2*d],2)+uo(n-l[2*d+1],2)<u)return d;break}}while(d!==f);return c}render(t){const e=null==t?t=new so: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=2*o[e],a=2*o[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 so:void 0,{points:r}=this;for(let 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Et(t,e,n){if(n.query.isoform&&yt[n.query.genome].genomicNameRegexp.test(n.query.isoform))return;const[r,o]=e.makequery(n.query);if(!r)return;const i=t.newconn.prepare(r).all(o);let s;s=e.tidy?i.map((t=>e.tidy(t))):i;const a={};if(e.isgeneexpression){a.lst=s,a.isgeneexpression=!0,a.config=e.config;for(const e of t.queries)if(e.dsblocktracklst)for(const t of e.dsblocktracklst)t.type==k.tkt.junction&&(a.config.dsjunctiontk=t)}else a.lst=s;return a}function Rt(t,e){const n=[u.join(o.tpmasterdir,t.vcffile),(t.vcf.nochr?e.query.range.chr.replace("chr",""):e.query.range.chr)+":"+e.query.range.start+"-"+e.query.range.stop];return new Promise(((e,r)=>{const o=m(vt,n),i=[],s=[];o.stdout.on("data",(t=>i.push(t))),o.stderr.on("data",(t=>s.push(t))),o.on("close",(n=>{""!=s.join("").trim()&&r("error querying vcf file");const o=i.join("").trim();e({lines:""==o?[]:o.split("\n"),vcfid:t.vcf.vcfid})}))}))}function It(t){if(!t.genome)return["no genome"];const e=yt[t.genome];if(!e)return["invalid 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r=Ht(e,t,i.checkrnabam);r&&r.dnacount.ishet&&n.hetsnps.push(r)}if(n.url?n.dir=await x.cache_index(n.url,n.indexURL||n.url+".bai"):n.file&&(n.file=u.join(o.tpmasterdir,n.file)),n.hetsnps.length>0){await Lt(n,n.hetsnps,e,i.checkrnabam);for(const e of n.hetsnps)e.rnacount.nocoverage||e.rnacount.ref+e.rnacount.alt<i.checkrnabam.rna_mintotalreads||l.push(t+"."+e.pos+"."+e.ref+"."+e.alt+"\t\t\t\t\t\t\t\t"+e.rnacount.ref+"\t"+e.rnacount.alt)}}l.length>0&&await async function(t,e){const n=await function(t){const e=u.join(o.cachedir,Math.random().toString());return new Promise(((n,r)=>{c.writeFile(e,t.join("\n")+"\n",(t=>{t&&r("cannot write"),n(e)}))}))}(t),r=await Ut(n);await function(t,e){return new Promise(((n,r)=>{c.readFile(t,"utf8",((t,o)=>{if(t&&r("cannot read binom pvalue"),o){for(const t of o.trim().split("\n")){const n=t.split("\t"),r=n[0].split("."),o=e[r[0]];if(!o)continue;const 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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=Gt(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 Bt(t,e,n,r,o,i){e.hideLOHwithCNVoverlap&&zt(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 grouping 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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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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 Vt(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 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Qt(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 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 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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&&zt(i);const c=[];for(const[t,e]of i)for(const t of e)c.push(t);s({id:t.id,items:c})}))}))))]}function oe(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]=ie(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]=re(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 ie(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 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i={};if(t.query&&t.query.genome)i[t.query.genome]=Tt(t.query.genome);else for(const t in yt)i[t]=Tt(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:xt.toDateString(),launchdate:kt,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})})),Nt.get(St+"/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,Nt,St)}):r.isMds?e.send({ds:jt(r)}):e.send({ds:Ct(r)})}catch(t){e.send({error:t.message||t})}})),Nt.all(St+"/genelookup",mt(yt)),Nt.post(St+"/ntseq",(async function(t,e){try{if(!t.query.coord)throw"coord 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n.refseq=e,n}))})}e.send({lst:o})}catch(t){e.send({error:t.message||t}),t.stack&&console.log(t.stack)}})),Nt.post(St+"/tkbedj",W(yt)),Nt.post(St+"/tkbedgraphdot",B(yt)),Nt.all(St+"/tkbam",z(yt)),Nt.get(St+"/gdcbam",$),Nt.get(St+"/gdc_ssms",U.handle_gdc_ssms(yt)),Nt.get(St+"/gdc_filter2topGenes",U.handle_filter2topGenes(yt)),Nt.get(St+"/tkaicheck",G(yt)),Nt.get(St+"/blat",J(yt)),Nt.all(St+"/mds3",Y(yt)),Nt.get(St+"/tkbampile",H),Nt.post(St+"/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 Rt(e,t);r.push(n)}else{if(!e.makequery)throw"unknow type from one of ds.queries[]";{const o=Et(n,e,t);r.push(o)}}e.send({data:r})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/tkbigwig",F),Nt.post(St+"/tkld",D(yt)),Nt.get(St+"/tabixheader",(async function(t,e){Mt(t);try{const[n,r,o]=ue(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})}})),Nt.post(St+"/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=Ot(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=Ot(e);o.push(t)}}}e.send({results:o})}catch(t){return t.stack&&console.log(t.stack),e.send({error:t.message||t})}})),Nt.get(St+"/clinvarVCF",(async function(t,e){Mt(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})}})),Nt.post(St+"/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)}})),Nt.post(St+"/dbdata",(function(t,e){})),Nt.get(St+"/img",(async function(t,e){Mt(t);const[n,r,o]=ue(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})}})),Nt.post(St+"/svmr",(function(t,e){if(t.query.file){const[n,r,o]=ue(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"})})),Nt.post(St+"/study",(async function(t,e){try{if(ce(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)ae(i[t]);delete r.mutationset,e.send({cohort:r,flagset:i})}catch(t){return void e.send({error:t.message||t})}})),Nt.post(St+"/textfile",(function(t,e){if(!t.query.file)return e.send({error:"no file"});if(ce(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.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 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Set(t.query.skip_termids||[]),o=new Map;for(const e in n.cohort.annotation){if(t.query.key){if(n.cohort.annotation[e][t.query.key]!=t.query.value)continue}o.set(e,new Map)}for(const[t,e]of o){const o=n.assayAvailability.samples.get(t);if(o)for(const t of n.assayAvailability.assays)r.has(t.id)||o[t.id]&&e.set(t.id,"yes")}for(const t of o.keys())0==o.get(t).size&&o.delete(t);const i={};i.totalsample=o.size,i.terms=ot({sample2term:o,terms:n.assayAvailability.assays,config:{termidorder:t.query.termidorder}}),e.send(i)}catch(t){e.send({error:t.message||t})}}(t,n,s);if(!s.queries)return n.send({error:"dataset is not equipped with queries"});if(a=s.queries[t.query.querykey],!a)return n.send({error:"invalid querykey"})}if(t.query.getexpression4gene)return async function(t,e,n,r,i){try{const n=t.query.getexpression4gene;if(!n.chr)throw"chr missing";if(!Number.isFinite(n.start))throw"invalid start pos";if(!Number.isFinite(n.stop))throw"invalid stop pos";if(!n.name)throw"unknown gene 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x.tabix_is_nochr(o,s,n)})}catch(t){t.stack&&console.error(t.stack),e.send({error:t.message||t})}})),Nt.post(St+"/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)}})),Nt.get(St+"/hicstat",(async function(t,e){Mt(t);try{const[n,r,o]=ue(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)}})),Nt.post(St+"/hicdata",(function(t,e){const[n,r,o]=ue(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})}))})),Nt.post(St+"/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]=Xt(e,n,t,r);if(i)throw"error with iscnv: "+i;o.push(s)}else if(e.isloh){const[i,s]=te(e,n,t,r);if(i)throw"error with isloh: "+i;o.push(s)}else if(e.isvcf){const[i,s]=ie(e,n,t,r);if(i)throw"error with isvcf: "+i;o.push(s)}else if(e.isitd){const[i,s]=ee(e,n,t,r);if(i)throw"error with isitd: "+i;o.push(s)}else if(e.issvfusion){const[i,s]=ne(e,n,t,r);if(i)throw"error with issvfusion: "+i;o.push(s)}else if(e.issvcnv){const[i,s]=re(e,n,t,r);if(i)throw"error with issvcnv: "+i;o.push(s)}else if(e.ismutation){const[t,s]=oe(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]=Kt(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)}))})),Nt.get(St+"/mdssamplescatterplot",(async function(t,e){Mt(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})}})),Nt.post(St+"/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})}})),Nt.post(St+"/mdssurvivalplot",lt(yt)),Nt.post(St+"/fimo",rt.handle_closure(yt)),Nt.all(St+"/termdb",P.handle_request_closure(yt)),Nt.all(St+"/termdb-barsql",L.handle_request_closure(yt)),Nt.post(St+"/singlecell",nt.handle_singlecell_closure(yt)),Nt.post(St+"/massSession",et.save),Nt.get(St+"/massSession",et.get),Nt.get(St+"/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})}})),Nt.post(St+"/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 Vt(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 Dt(t,n.chr,e):await Ft(t,n.chr,e),e.fpkm=1e9*r/(n.rnabamtotalreads*e.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 Jt(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 Wt(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=Ht(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.width*t.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.rnabarheight*Math.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 Ut(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})}})),Nt.post(St+"/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})}})),Nt.get(St+"/gene2canonicalisoform",(function(t,e){Mt(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)}})),Nt.get(St+"/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"}}(),xt=function(){const t=c.statSync(o.binpath+"/server.js").mtime,e=c.existsSync("public/bin/proteinpaint.js")&&c.statSync("public/bin/proteinpaint.js").mtime||0;return t>e?t:e}(),kt=Date(Date.now()).toString().split(" ").slice(0,5).join(" "),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 pe("massSession"),o.cachedir_massSessionTrash=await pe("massSessionTrash"),o.cache_snpgt={dir:await pe("snpgt"),fileNameRegexp:/[^\w]/,sampleColumn:6},o.cachedir_bam=await pe("bam"),o.cachedir_genome=await pe("genome"),o.cachedir_ssid=await pe("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);if(yt[t.name]=n,!n.genomefile)throw".genomefile missing from .js file of genome "+t.name;if("NA"==n.genomefile||(n.genomefile=u.join(o.tpmasterdir,n.genomefile)),n.genomicNameRegexp||(n.genomicNameRegexp=/[^a-zA-Z0-9.:_-]/),n.tracks||(n.tracks=[]),t.tracks)for(const e of t.tracks)n.tracks.push(e);if(t.datasets&&(n.rawdslst=t.datasets),t.snp&&(n.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;n.blat=t.blat}if(t.nosnp&&delete n.snp,t.nohicenzyme&&delete n.hicenzymefragment,t.nohicdomain&&delete n.hicdomain,n.genedb&&t.no_gene2canonicalisoform&&delete n.genedb.gene2canonicalisoform,t.updateAttr)for(const e of t.updateAttr){let t=n;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]=fe(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):o;if(K(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,Nt,St)}catch(t){throw t.stack&&console.log(t.stack),"Error with mds3 dataset "+i.label+": "+t}else if(i.isMds)try{await ge(i,n,e)}catch(t){throw"Error with mds dataset "+i.label+": "+t}else he(i,n)}de(),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=>Nt.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,Nt);return r.listen(t,"0.0.0.0",(()=>{console.log(`HTTPS ${e}`)})),r}{const n=await a.createServer(Nt);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=Mt,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(3*e/4)].value,i=t[Math.floor(.05*e)].value,s=t[Math.floor(.95*e)].value,a=(t[Math.floor(.01*e)].value,o-r);let l,c;if(0==a)l=0,c=0;else{const n=t.findIndex((t=>t.value>r-1.5*a));l=t[-1==n?0:n].value;const i=t.findIndex((t=>t.value>o+1.5*a));c=t[-1==i?e-1:i-1].value}const u=t.filter((t=>t.value<r-1.5*a||t.value>o+1.5*a));return{w1:l,w2:c,p05:i,p25:r,p50:n,p75:o,p95:s,iqr:a,out:u}};function ae(t){delete t.mclasslabel2key,delete t.sample2disease,delete t.patient2ori2sample}const le=Object.freeze([".bam",".bai",".gz",".tbi",".csi",".bw",".bb"]);function ce(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]&&gt(t,n)){e=!1;break}if("!"==n[0]&&!gt(t,n)){e=!0;break}}if(e)return!0}if(n)for(const e of le)if(e===u.extname(t).toLowerCase())return!0;return!1}function ue(t,e=!0){let n=null,r=!1;if(t.query.file){if(n=t.query.file,ce(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 fe(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 de(){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 he(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 "+genomename+"."+t.label;if(0==t.cohort.levels.length)throw"levels is blank array for cohort of "+genomename+"."+t.label;for(const e of t.cohort.levels)if(!e.k)throw".k key missing in one of the levels, .cohort, in "+genomename+"."+t.label}if(t.cohort.fromdb){if(!t.cohort.fromdb.sql)throw".sql missing from ds.cohort.fromdb in "+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 "+genomename+"."+t.label;const r=c.readFileSync(u.join(o.tpmasterdir,n.file),"utf8").trim();if(!r)throw n.file+" is empty for "+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 "+genomename+"."+t.label;if(!t.cohort.key4annotation)throw".cohort.key4annotation missing when .cohort.tosampleannotation is on for "+genomename+"."+t.label}}if(!t.queries)throw".queries missing from dataset "+t.label+", "+genomename;if(!Array.isArray(t.queries))throw t.label+".queries is not array";for(const n of t.queries){const r=me(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 pe(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 me(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 ge(t,e,n){if((t.isMds2||t.isMds3||t.isMds)&&K(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 Q.init_db(t,Nt,St),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]=fe(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]=fe(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=ve(o,t,e);if(n)throw r+" (mdsjunction) error: "+n}else if(o.type==k.tkt.mdscnv){const n=we(o,t,e);if(n)throw r+" (mdscnv) error: "+n}else if(o.type==k.tkt.mdssvcnv){const n=xe(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 qe(o,t,e);if(n)throw r+" (vcf) error: "+n}}ye(o,t)}else{if(!o.isgenenumeric)throw"unknown type of query from "+r;{const n=ke(o,t,e);if(n)throw r+" (genenumeric) error: "+n}}}if(t.track&&await Q.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 ye(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 ve(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]=se(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=be(t.samples,e),t.hierarchySummary=_e(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 be(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 _e(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 we(t,e,n){let r;if(t.file){const[e,n]=se(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=be(t.samples,e),t.hierarchySummary=_e(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+": "+(t.samples?t.samples.length:"no")+" samples, "+(t.nochr?'no "chr"':'has "chr"'))}function xe(t,e,n){let r;if(t.file){const[e,n]=se(t.file);if(e)return"tabix file error: "+e;r=n}else{if(!t.url)return"no file or url given for (svcnv) "+t.name;r=t.url}const o={encoding:"utf8"};const i=p.execSync(vt+" -H "+r,o).trim();if(i){const n=new Set;for(const t of i.split("\n"))for(const e of t.split(" ").slice(1))n.add(e);if(0==n.size)return"no samples from the header line";if(t.samples=[...n],e.cohort&&e.cohort.annotation){const n=new Set;for(const r of t.samples)e.cohort.annotation[r]||n.add(r);n.size&&console.log("mdssvcnv unannotated samples: "+(t.noprintunannotatedsamples?n.size:[...n].join(" ")))}}{const e=p.execSync(vt+" -l "+r,o).trim();if(!e)return"no chromosomes found";t.nochr=k.contigNameNoChr(n,e.split("\n"))}if(t.expressionrank_querykey){const n=e.queries[t.expressionrank_querykey];if(!n)return"invalid key by expressionrank_querykey";if(!n.isgenenumeric)return"query "+t.expressionrank_querykey+" not tagged as isgenenumeric"}if(t.vcf_querykey){const n=e.queries[t.vcf_querykey];if(!n)return"invalid key by vcf_querykey";if(n.type!=k.tkt.mdsvcf)return"query "+t.vcf_querykey+" not of mdsvcf type"}if(t.groupsamplebyattr){if(!t.groupsamplebyattr.attrlst)return".attrlst[] missing from groupsamplebyattr";if(0==t.groupsamplebyattr.attrlst.length)return"groupsamplebyattr.attrlst[] empty array";if(!e.cohort)return"groupsamplebyattr in use but ds.cohort missing";if(!e.cohort.annotation)return"groupsamplebyattr in use but ds.cohort.annotation missing";e.cohort.sampleAttribute||(e.cohort.sampleAttribute={}),e.cohort.sampleAttribute.attributes||(e.cohort.sampleAttribute.attributes={},console.log("cohort.sampleAttribute added when groupsamplebyattr is in use"));for(const n of t.groupsamplebyattr.attrlst){if(!n.k)return"k missing from one of groupsamplebyattr.attrlst[]";e.cohort.sampleAttribute.attributes[n.k]||(e.cohort.sampleAttribute.attributes[n.k]={label:n.label||n.k})}if(t.groupsamplebyattr.sortgroupby){if(!t.groupsamplebyattr.sortgroupby.key)return".key missing from .sortgroupby";if(!t.groupsamplebyattr.sortgroupby.order)return".order[] missing from .sortgroupby";if(!Array.isArray(t.groupsamplebyattr.sortgroupby.order))return".order must be an array"}t.groupsamplebyattr.attrnamespacer||(t.groupsamplebyattr.attrnamespacer=", ")}console.log("("+t.type+") "+t.name+": "+(t.samples?t.samples.length:"no")+" samples, "+(t.nochr?'no "chr"':'has "chr"'))}function ke(t,e,n){if(!t.datatype)return"datatype missing";if(t.viewrangeupperlimit&&Number.isNaN(t.viewrangeupperlimit))return"invalid value for viewrangeupperlimit";let r;if(!t.file)return"file missing";{const[e,n]=se(t.file);if(e)return"tabix file error: "+e;r=n}const o={cwd:null,encoding:"utf8"};{const e=p.execSync(vt+" -H "+r,o).trim();if(!e)return"no header line (#sample <sample1> ...)";const n=new Set;for(const t of e.split("\n")){const e=t.split(" ");for(let t=1;t<e.length;t++)n.add(e[t])}if(0==n.size)return"no sample names from header line";t.samples=[...n],console.log("(genenumeric) "+t.name+": "+t.samples.length+" samples")}if(t.boxplotbysamplegroup){if(!t.boxplotbysamplegroup.attributes)return"boxplotbysamplegroup.attributes missing";if(!Array.isArray(t.boxplotbysamplegroup.attributes))return"boxplotbysamplegroup.attributes should be array";for(const e of t.boxplotbysamplegroup.attributes)if(!e.k)return"k missing from one of boxplotbysamplegroup.attributes[]"}}async function qe(t,e,n){if(!t.tracks)return"tracks[] missing";if(!Array.isArray(t.tracks))return"tracks should be array";t.info={};for(const r of t.tracks){if(!r.file)return"file missing from a track (url not supported yet)";const[o,i]=se(r.file);if(o)return"tabix file error: "+o;if(r.type!=k.mdsvcftype.vcf)return"invalid track type: "+r.type;{r.cwd;const e=await x.get_header_tabix(i,r.cwd);if(0==e.length)return"no meta/header lines for "+i;const[n,o,s,a]=q.vcfparsemeta(e);if(a)return"error parsing vcf meta for "+i+": "+a.join("\n");if(0==s.length)return"vcf file has no sample: "+i;for(const e in n)t.info[e]=n[e];if(r.format=o,r.samplenameconvert){if("function"!=typeof r.samplenameconvert)return".samplenameconvert must be function";for(const t of s)t.name=r.samplenameconvert(t.name)}r.samples=s}if(e.cohort&&e.cohort.annotation){const t=[];for(const n of r.samples)e.cohort.annotation[n.name]||t.push(n.name);t.length&&console.log(e.label+": VCF "+r.file+" has unannotated samples: "+t.join(","))}{const t=[];if(await x.get_lines_bigfile({args:["-l",i],dir:r.cwd,callback:e=>{t.push(e)}}),0==t.length)return"no chr from "+i;r.nochr=k.contigNameNoChr(n,t)}console.log("("+t.type+") "+i+": "+r.samples.length+" samples, "+(r.nochr?"no chr":"has chr"))}if(t.singlesamples){if(!t.singlesamples.tablefile)return".singlesamples.tablefile missing for the VCF 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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 dt(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 ht(t,e){for(const t of e.regions)t.lines.length>0&&t.ntwidth>=.9&&(t.to_checkmismatch=!0,t.referenceseq=await vt(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),xt(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 pt(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=mt(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=mt(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 mt(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)&&a*e.ntwidth>=1&&_.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 gt(t,e,n){const[r,o]=function(t,e){let n=(e.groups.length>1?750:rt)/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>=1;if(t.stacks.length&&(t.stackheight>=7&&n.length<2e3?t.returntemplatebox=[]:t.partstack||(t.allowpartstack=!0)),t.stackheight>=7){let e=0;for(const t of n)for(const n of t.segments)e=Math.max(e,n.x2-n.x1);e>.7*t.stackheight&&(t.canClipArrowhead=!0)}}function yt(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 vt(t,e){const n=(await d.get_fasta(t,e)).split("\n");return n.shift(),n.join("").toUpperCase()}function bt(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<=.4)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=wt(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?_t(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 _t(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 wt(t,e){if(2==t.segments.length){const[n,r]=t.segments;return n.x2>r.x1?(r.shiftdownrow=1,2*e):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 e*n.length}function xt(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 kt(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){qt(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){qt(t,i,e.y,n,r);const o=Math.floor(e.y+n.stackheight/2)+.5;if(t.strokeStyle=n.stackheight<=2?U: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=G,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(qt(t,i,e.y+n.stackheight,n,r),n.overlapRP_hlline){const r=Math.floor(e.y+n.stackheight)+.5;t.strokeStyle=G,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 qt(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 qt(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=L: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=L:e.discord_wrong_insertsize?t.fillStyle=T:e.discord_unmapped2?t.fillStyle=F:t.fillStyle=q,s+o.len*i.ntwidth+et<i.width&&s<i.width&&i.x<s+et?t.fillRect(s,n,o.len*i.ntwidth+et,r.stackheight):s+o.len*i.ntwidth+et<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+et+s-i.x,r.stackheight):s+o.len*i.ntwidth+et>=i.width&&i.x<s?t.fillRect(s,n,i.width-s,r.stackheight):s+o.len*i.ntwidth+et>=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]/tt;t.fillStyle="S"==o.opr?P(a):E(a),e+i.ntwidth+et<i.x+i.width&&i.x<=e?t.fillRect(e,n,i.ntwidth+et,r.stackheight):e<i.x+i.width&&e+i.ntwidth+et>=i.x+i.width&&i.x<=e?t.fillRect(e,n,i.width+i.x-e,r.stackheight):e<=i.x&&e+i.ntwidth+et>i.x&&t.fillRect(i.x,n,i.ntwidth+et+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.len*i.ntwidth+et<i.width&&i.x<s?t.fillRect(s,n,o.len*i.ntwidth+et,r.stackheight):s+o.len*i.ntwidth+et<i.width&&i.x>=s?t.fillRect(i.x,n,o.len*i.ntwidth+et+s-i.x,r.stackheight):s+o.len*i.ntwidth+et<=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=D(o/tt)),t.fillRect(a,n,i.ntwidth+et,r.stackheight),a+=i.ntwidth}))}else e.discord_unmapped2&&(t.fillStyle=F),t.fillRect(s,n,o.len*i.ntwidth+et,r.stackheight);i.to_printnt&&(t.font=Math.min(i.ntwidth,r.stackheight-2)+"pt Arial")}else{"D"==o.opr?t.strokeStyle="black":t.strokeStyle=r.stackheight<=2?U: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.len*i.ntwidth,i.x+i.width),e),t.stroke(),r.stackheight>7){const e=Math.max(i.x,s),a=Math.min(i.x+i.width,s+o.len*i.ntwidth);if(a-e>=50){const s=Math.min(10,Math.max(7,r.stackheight-2));t.font=s+"pt Arial";const l=t.measureText(o.len+" bp").width;l<a-e-20&&(t.fillStyle="white",(a+e)/2+l/2<i.width&&i.x<(a+e)/2-l/2?(t.fillRect((a+e)/2-l/2,n,l,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)):(a+e)/2+l/2<i.width&&i.x>=(a+e)/2-l/2?(t.fillRect(i.x,n,l+(a+e)/2-l/2-i.x,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)):(a+e)/2+l/2>=i.width&&i.x<(a+e)/2-l/2&&(t.fillRect((a+e)/2-l/2,n,i.width-(a+e)/2+l/2,r.stackheight),t.fillStyle=q,t.fillText(o.len+" bp",(a+e)/2,n+r.stackheight/2)))}}}}!function(t,e,n,r,o){if(!n.canClipArrowhead)return;if(e.x2-e.x1<5)return;if(e.forward){const i=Math.ceil(e.x2+et);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(12,Math.max(7,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 Nt(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(12,e.stackheight-2)+"pt Arial";for(const s of i){const i=o.x+o.scale(s.start);s.qual?t.fillStyle=$(s.qual.reduce(((t,e)=>t+e),0)/s.qual.length/tt):t.fillStyle=z;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 St(t,e,n){const r=_t(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]/tt)+'">'+t.seq[e.cidx+n]+"</td>")}const i=[];i.push('<li><span style="background:#6B4423;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 At(t,e,n){const r=t.boxes[0].start,o=t.boxes[t.boxes.length-1],i=o.start+o.len,s=await vt(e,n.chr+":"+(r+1)+"-"+i),a=_t(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]/tt)+'">'+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]/tt)+'">'+t.seq[e.cidx+n]+"</td>");else if(e.len>=20)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:#47FFFC;background:white">'+t.seq[n]+"</td>"):c.push('<td style="color:#47FFFC;background:'+S(a[n]/tt)+'">'+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:#d48b37">'+(n.nochr?"chr":"")+t.rnext+", "+t.pnext+"</span></li>"),t.discord_wrong_insertsize&&t.discord_orientation?m.push('<li><span style="background:#3B7A57;color:white">Wrong insert size</span> mate position: '+t.pnext+'</li><li><span style="background:'+'#fc6df3;color:white">Segments also having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_wrong_insertsize?m.push('<li><span style="background:#3B7A57;color:white">Wrong insert size</span> mate position: '+t.pnext+"</li>"):t.discord_orientation?m.push('<li><span style="background:#fc6df3;color:white">Segments having wrong orientation</span> '+t.discord_orientation_direction+"</li>"):t.discord_unmapped2&&m.push('<li><span style="background:#6B4423;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:20};return 1==p&&(g.soft_starts=d,g.soft_stops=h),t.discord_unmapped2&&(g.unmapped_mate=!0),g}function Mt(t){const e=i.createHmac("md5",it),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 Tt(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 Ct(r.chr,r.start,r.stop,t.get("X-Auth-Token"),t.query.gdcFileUUID,Mt(t),t.cookies.sessionid);n.push({filesize:e})}return n}async function Ct(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=ot+"/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=Mt(e),e.query.isFileSlice=!0}if(e.query.downloadgdc)return void n.send(await Tt(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 lt(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=mt({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 St(n,t,e.query)):i.push(await At(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 lt(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[4*e],pos:Number(t[4*e+1]),ref:t[4*e+2],alt:t[4*e+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(2,5*o),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(1.5*Math.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 ut(t,[s]),await ft(s,t),void(t.regions[0].lines=s.lines)}await ut(t,t.regions);for(const e of t.regions)await ft(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=pt(t,e);return n=yt(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 ct(n,o,t.partstack.start,t.partstack.stop,e.refseqs[0]):await ct(n,o,0,0,e.refseqs[0])}else if("support_no"==t.type){let o=e.leftflankseqs[0].length;r=t.partstack?await ct(n,o,t.partstack.start,t.partstack.stop):await ct(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 ct(n,i,t.partstack.start,t.partstack.stop,e.altseqs[o]):await ct(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=pt(t,r);o=yt(r,t,o),await gt(r,t,o),await ht(o,t),bt(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.canvaswidth*t.devicePixelRatio,r.canvasheight*t.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)kt(a,e,r,t);Nt(a,r,t,o),t.asPaired&&(i.count.t=o.length),t.variant&&(i.diff_scores_img=await st(t,r,o,e.max_diff_score,e.min_diff_score),"support_alt0"==i.type?i.group_color=V:"support_alt1"==i.type?i.group_color=W:"support_alt2"==i.type?i.group_color=J:"support_alt3"==i.type?i.group_color=Y:"support_alt4"==i.type?i.group_color=K:"support_alt5"==i.type?i.group_color=Q:"support_ref"==i.type&&(i.group_color=X)),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=2*o+i+a+4*(n+r),u=p(t.devicePixelRatio*l,t.devicePixelRatio*c),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=2*o+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+3*e/4,d),f.lineTo(s+3*e/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+3*e/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(Z,z,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.canvaswidth*t.devicePixelRatio,t.pileupheight*t.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 dt(t,r),at(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=H;const e=i.total*s;r.fillRect(o,t.pileupheight-e,a,e)}let l=0;if(i.A){r.fillStyle=b.A;const e=i.A*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.C){r.fillStyle=b.C;const e=i.C*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.G){r.fillStyle=b.G;const e=i.G*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.T){r.fillStyle=b.T;const e=i.T*s;r.fillRect(o,t.pileupheight-l-e,a,e),l+=e}if(i.softclip){r.fillStyle=R;const e=i.softclip*s;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 u=Number(t.query.allheight),f=Number(t.query.fineheight),d=Number(t.query.fineymax),h=Number(t.query.midpad),p=Number(t.query.regionspace),m=Number(t.query.width);if(!Number.isInteger(u))throw"allheight is not integer";if(!Number.isInteger(f))throw"fineheight is not integer";if(!Number.isInteger(d))throw"fineymax is not integer";if(!Number.isInteger(h))throw"midpad is not integer";if(!Number.isInteger(p))throw"regionspace is not integer";if(!Number.isFinite(m))throw"width is not a number";const g="string"==typeof t.query.rglst?JSON.parse(t.query.rglst):t.query.rglst;if(!g)throw"no rglst[]";if(!Array.isArray(g))throw"rglst is not an array";if(0==g.length)throw"empty rglst";for(const t of g)t.reverse?t.scale=e=>Math.ceil(t.width*(t.stop-e)/(t.stop-t.start)):t.scale=e=>Math.ceil(t.width*(e-t.start)/(t.stop-t.start));let y;l&&(y=await o.cache_index(a,t.query.indexURL));for(const t of g){t.items=[];let e=0;await 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r)a.push({nt:t,v:r[t]}),i+=r[t];w.fillStyle=q;const l=S*(k-i);if(w.fillRect(N+o,l,e,S*i),a.length>1){a.sort(((t,e)=>e.v-t.v));for(let t=1;t<a.length;t++){let n=0;for(let e=0;e<t;e++)n+=a[e].v;w.fillStyle=s[a[t].nt],w.fillRect(N+o,l+S*n,e,S*a[t].v)}}w.fillStyle=q;const f=u+h+A*(d-Math.min(i,d));if(w.fillRect(N+o,f,e,A*Math.min(i,d)),a.length>1)for(let t=1;t<a.length;t++){let n=0;for(let e=0;e<t;e++)n+=a[e].v;w.fillStyle=s[a[t].nt],w.fillRect(N+o,f+A*(d-Math.min(d,i-n)),e,A*Math.min(d,a[t].v))}}N+=t.width+p}e.send({src:b.toDataURL(),allgrades:x,usegrade:c,allmax:k})}catch(t){t.stack&&console.log(t.stack),e.send({error:t.message||t})}}},2388:(t,e,n)=>{const r=n(9699),o=n(1017),i=(n(7147),n(3856)),s=n(6718).createCanvas,a=n(334);async function l(t,e,n){const o={rglst:[]};let a=0,l=0;if(t.autoscale){for(const r of t.rglst){const o=(n?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;await i.get_lines_bigfile({args:[t.file,o],dir:e,callback:t=>{const[e,n,r,o]=t.split("\t");for(const t of o.split(",")){const e=Number(t);a=Math.min(a,e),l=Math.max(l,e)}}})}o.minv=a,o.maxv=l}else a=t.minv,l=t.maxv;const c=r.makeyscale().height(t.barheight).min(a).max(l);for(const r of t.rglst){const u={chr:r.chr,start:r.start,stop:r.stop,width:r.width,reverse:r.reverse,xoff:r.xoff},f=s(r.width,t.barheight),d=f.getContext("2d"),h=(n?r.chr.replace("chr",""):r.chr)+":"+r.start+"-"+r.stop;await i.get_lines_bigfile({args:[t.file,h],dir:e,callback:e=>{const[n,o,i,s]=e.split("\t"),u=Math.max(Number.parseInt(o),r.start),f=Math.min(Number.parseInt(i),r.stop),h=(r.reverse?r.stop-f:u-r.start)*r.width/(r.stop-r.start),p=(r.reverse?r.stop-u:f-r.start)*r.width/(r.stop-r.start);for(const e of s.split(",")){const n=Number(e);d.fillStyle=n>0?t.pcolor:t.ncolor;const r=c(n),o=Math.max(1,p-h);d.fillRect(h,r.y,o,2),n>l?(d.fillStyle=req.query.pcolor2,d.fillRect(h,0,o,2)):n<a&&(d.fillStyle=req.query.ncolor2,d.fillRect(h,t.barheight-2,o,2))}}}),u.img=f.toDataURL(),o.rglst.push(u)}return 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-2*s<a)return;const c=Math.ceil((o-2*s)/(a+l));if(c<=0)return;const u="+"==e;let f=Math.ceil(n+(o-a*c-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,y*t.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,y*t.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-2*O),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-2*O))}}}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=[],D=i(10,10);let L=D.getContext("2d");t.query.devicePixelRatio>1&&L.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);L.font="bold "+w+"px Arial";const B=j.length<l,z=j.length<l?[]:null;let Z=!1;k&&(Z=k.reverse);for(const e of t.query.rglst)e.reverse&&(Z=!0);j.sort(((t,e)=>Z?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 $=j.some((t=>t.exon)),U=[0];let G=1,H=null;for(const e of j){let n=null,r=null;for(const o of e.rglst){let i=0;for(let e=0;e<o.idx;e++)i+=t.query.rglst[e].width+b;const s=t.query.rglst[o.idx],a=Math.max(e.start,s.start),l=Math.min(e.stop,s.stop);if(a<l){const t=i+s.scale(s.reverse?l:a),e=i+s.scale(s.reverse?a:l);null==n?(n=t,r=e):(n=Math.min(n,t),r=Math.max(r,e))}}if(null==n)continue;e.canvas={start:n,stop:r,stranded:null!=e.strand},e.coding&&I&&(e.willtranslate=!0,F.push(e));let o=n,i=r;if(B){const t=e.name;if(t){e.canvas.namestr=t;const n=L.measureText(t).width;e.canvas.namewidth=n,$?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*_&&(H=[]);for(let t=1;t<=G;t++)if(null==U[t]||U[t]<o){e.canvas.stack=t,U[t]=i;break}null==e.canvas.stack&&(G++,U[G]=i,e.canvas.stack=G),h(z,o,i,e.canvas.stack,e)}D.width=_*t.query.devicePixelRatio;const V=(y+v)*G-v;D.height=V*t.query.devicePixelRatio,L=D.getContext("2d"),t.query.devicePixelRatio>1&&L.scale(t.query.devicePixelRatio,t.query.devicePixelRatio);L.font="bold "+w+"px Arial",L.textBaseline="middle",L.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);L.fillStyle=r,(e.exon||e.rglst.length>1)&&(L.strokeStyle=r,L.beginPath(),L.moveTo(n.start,Math.floor(o+y/2)+.5),L.lineTo(n.stop,Math.floor(o+y/2)+.5),L.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){L.fillStyle=t.color;break}const t=s+a.scale(a.reverse?i:n),l=s+a.scale(a.reverse?n:i);L.fillRect(t,o+O,Math.max(1,l-t),y-2*O),e.exon2color&&(L.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){L.fillStyle=t.color;break}const t=s+a.scale(a.reverse?l:i),c=s+a.scale(a.reverse?i:l);if(L.fillRect(t,o,Math.max(1,c-t),y),e.exon2color&&(L.fillStyle=r),n.stranded&&!e.willtranslate)if(L.strokeStyle="white",n.namein){const e=(c-t-n.namewidth)/2;p(L,u,t,o+O,e,y-2*O),p(L,u,t+e+n.namewidth,o+O,e,y-2*O)}else p(L,u,t,o+O,c-t,y-2*O)}}if(n.stranded&&e.intron){L.strokeStyle=r;for(const t of e.intron){const 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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{} 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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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isoform";if(null===(l=t.genome)||void 0===l||null===(u=l.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"}})),r&&(e.some((t=>"case.submitter_id"==t.id))||e.push({term:{id:"case.submitter_id"}})),e.some((t=>"case.case_id"==t.id))||e.push({term:{id:"case.case_id"}})),"summary"!=t.get&&"sunburst"!=t.get||e.some((t=>"case.submitter_id"==t.id))||e.push({term:{id:"case.submitter_id"}});const f=[];for(const t of e){const e=n.cohort.termdb.q.termjsonByOneid(t.term.id);e&&f.push({term:e})}const d=e.map((t=>t.term.id));t.hiddenmclass&&(d.push("ssm.consequence.transcript.consequence_type"),d.push("ssm.consequence.transcript.transcript_id")),t.rglst&&(d.push("ssm.chromosome"),d.push("ssm.start_position"));const h={size:1e4,fields:d.join(",")};g(t,n),h.filters=F.filters(t,n);const p=w(t),m=await o.post(i.join(c,F.endpoint),{headers:p,body:JSON.stringify(h)});let y;delete t.isoforms;try{y=JSON.parse(m.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 b=[];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 _;if(!Array.isArray(null===(_=e.ssm)||void 0===_?void 0:_.consequence))continue;const n={};if(v(n,e.ssm.consequence.find((e=>e.transcript.transcript_id==t.isoform))),t.hiddenmclass.has(n.class))continue}if(t.rglst){var q,M;if(null===(q=e.ssm)||void 0===q||!q.chromosome||null===(M=e.ssm)||void 0===M||!M.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 T,C,j,O;if(r.sample_id=await N(e.case,n,!0),e.case.case_id)r.sample_URLid=e.case.case_id,null!==(T=e.case)&&void 0!==T&&null!==(C=T.observation)&&void 0!==C&&null!==(j=C[0])&&void 0!==j&&null!==(O=j.sample)&&void 0!==O&&O.tumor_sample_uuid&&(r.sample_URLid=r.sample_URLid+"?bioId="+e.case.observation[0].sample.tumor_sample_uuid);for(const t of f)x(r,e.case,t.term);S(e.case,r),A(r,n),b.push(r)}if(r){const t={gene:r.map((t=>t.term.name)).join(","),twLst:f},e=await n.queries.geneCnv.bygene.get(t);for(const t of e)for(const e of t.samples)b.push(e)}const E=new Map;for(const t of b)a([t],E,t.ssm_id);return[...E.values()]}async function N(t,e,n){var r,o,i;return n&&t.submitter_id?t.submitter_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 S(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 A(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 M(t,e,n,r){k(t);const i=[];for(const e of t)e.term&&"categorical"==e.term.type&&i.push({id:e.id,path:e.id.replace("case.","").replace(/\./g,"__"),type:e.term.type});const s=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 }}")}return`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}`}(i),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(",")}});return n}(e,r),l=await o.post(u,{headers:w(e),body:JSON.stringify({query:s,variables:a})});let c;try{c=JSON.parse(l.body)}catch(t){throw"invalid JSON from GDC for cohortTotal for query :"+s+" and filter: "+filter}const f=["data","explore","cases","aggregations"];let d=c[f[0]];for(let t=1;t<f.length;t++)if(d=d[f[t]],!d)throw"."+f[t]+" missing from data structure of termid2totalsize2 for query :"+s+" and filter: "+filter;for(const t of i){if("categorical"==t.type&&!Array.isArray(d[t.path].buckets))throw f.join(".")+" not array for query :"+s+" and filter: "+filter;if(("integer"==t.type||"float"==t.type)&&"object"!=typeof d[t.path].stats)throw f.join(".")+" not object for query :"+s+" and filter: "+filter}const h=new Map;for(const t of i)if("categorical"==t.type){const e=d[t.path].buckets;let n=[];for(const t of e)n.push([t.key.replace(".","__"),t.doc_count]);h.set(t.id,n)}else if("integer"==t.type||"float"==t.type){const e=d[t.path].stats.count;h.set(t.id,{total:e})}return n?[h,n]:h}function T(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 o(c+"/ssms/"+t.ssm_id+"?fields="+e.join(","),{method:"GET",headers:w(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 C(t,e){t.queries.singleSampleMutation.get=async(n,r)=>{if(!n)throw"case_id missing";return r.case_id=n,await O(r,t,e)}}function j(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 O(e.query,o,r)})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function O(t,e,n){const s=[];{const e=await o.post(i.join(c,P.endpoint),{headers:w(t),body:JSON.stringify({size:1e3,fields:P.fields.join(","),filters:P.filters(t)})}),a=JSON.parse(e.body);for(const t of a.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 o=n.genedb.get_gene2canonicalisoform.get(e);if(null==o||!o.isoform)continue;let i=t.consequence.find((t=>t.transcript.transcript_id==o.isoform));i||(i=t.consequence[0]);const a=i.transcript.aa_change||i.transcript.consequence_type,[l,c,u]=r.vepinfo(i.transcript.consequence_type);s.push({dt:r.dtsnvindel,mname:a,class:c,gene:i.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=w(t),n=await o.post(i.join(c,"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)})}),s=JSON.parse(n.body);if(!Array.isArray(s.data.hits))throw"re.data.hits[] not array";let a,l,u;for(const t of s.data.hits)if("BEDPE"!=t.data_format){if("TXT"==t.data_format){if("Genotyping Array"==t.experimental_strategy){var f,d,h;const e=null===(f=t.cases)||void 0===f||null===(d=f[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;a=t.file_id;continue}if("WGS"==t.experimental_strategy){if(!t.file_id)continue;if("Copy Number Segment"!=t.data_type)continue;l=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;u=t.file_id}const m=[];if(l){const t=(await o(i.join(c,"data")+"/"+l,{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(a){const t=(await o(i.join(c,"data")+"/"+a,{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(u)try{const t=(await o(i.join(c,"data")+"/"+u,{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)&&(_(o,n[6]),m.push(o))}}catch(t){}return m}(t);s.push(...e)}return s}function E(t){return async(e,n)=>{try{if(!t[e.query.genome])throw"invalid genome";n.send({genes:await R({filter:e.query.filter0,CGConly:e.query.CGConly,maxGenes:e.query.maxGenes})})}catch(t){t.stack&&console.log(t.stack),n.send({error:t.message||t})}}}async function R({filter:t,CGConly:e,maxGenes:n}){if(!t)throw"filter missing";if("object"!=typeof t)throw"filter not object";const r=await o.post(i.join(c,"/analysis/top_mutated_genes_by_project"),{headers:{"Content-Type":"application/json",Accept:"application/json"},body:JSON.stringify({size:n||50,fields:"symbol",filters:I(t,e)})}),s=JSON.parse(r.body),a=[];for(const t of s.data.hits)t.symbol&&a.push(t.symbol);return a}function I(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 P={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(l(t.filterObj)),e}},F={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(l(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}}},9535:(t,e,n)=>{"use strict";n.r(e),n.d(e,{client_copy:()=>E,cnvByRangeGetter_file:()=>V,init:()=>O,snvindelByRangeGetter_bcf:()=>F,ssmIdFieldsSeparator:()=>T,svfusionByRangeGetter_file:()=>H,validate_termdb:()=>R});const r=n(5243),o=n(7147),i=n(4521),s=n(1017),a=n(2282).scaleLinear,l=n(6718).createCanvas,{initGDCdictionary:c}=n(1778),{validate_variant2samples:u}=n(817),f=n(3856),d=n(3625).compute_mclass,h=n(334),{dtsnvindel:p,dtfusionrna:m,dtsv:g,dtcnv:y,mclassfusionrna:v,mclasssv:b,mclasscnvgain:_,mclasscnvloss:w}=n(2273),{get_samples:x}=n(2852),{server_init_db_queries:k}=n(394),{barchart_data:q}=n(1711),{setDbRefreshRoute:N}=n(1883),S=n(2188).wz,A=n(2974).mayInitiateMatrixplots,{add_bcf_variant_filter:M}=n(3795),T=".",C="Ancestry_PC_",j="Unannotated";async function O(t,e,n,o=null,i=null){var a,l;await R(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)r.validate_query_snvindel_byrange(t);else if(n.byrange.bcffile){var o;n.byrange.bcffile=s.join(h.tpmasterdir,n.byrange.bcffile),n.byrange._tk={file:n.byrange.bcffile},n.byrange.get=await F(t,e),null!==(o=n.byrange._tk)&&void 0!==o&&o.samples.length||delete n.byrange._tk.samples,P(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:s.join(h.tpmasterdir,n.byrange.chr2bcffile[t])};delete n.byrange.chr2bcffile,n.byrange.get=await F(t,e),n.byrange._tk.samples.length||delete n.byrange._tk.samples,P(t,n.byrange._tk.samples,"snvindel.byrange.bcffile")}if(n.byisoform){if(!n.byisoform.gdcapi)throw"unknown query method for queries.snvindel.byisoform";r.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";r.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=s.join(h.tpmasterdir,n.byrange.file),n.byrange.get=await H(t,e),P(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&&r.validate_query_geneCnv(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=s.join(h.tpmasterdir,n.byrange.file),n.byrange.get=await V(t,e),P(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=s.join(h.tpmasterdir,t.file),await f.validate_tabixfile(t.file),t.nochr=await f.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 r.validate_query_geneExpression(t);if(!n.file)throw".file missing from queries.geneExpression";n.file=s.join(h.tpmasterdir,n.file),await f.validate_tabixfile(n.file),n.nochr=await f.tabix_is_nochr(n.file,null,e),n.get=async e=>{let r;{const n=await z(e,null,t);n&&(r=new Set(n.map((t=>t.name))))}const o=new Map;for(const t of e.genes)o.set(t.gene,{}),await f.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)r.validate_query_singleSampleMutation(t,e);else{if(!n.folder)throw"unknown query method for singleSampleMutation";n.get=async e=>{var r,o,i;let a=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&&(a=t.cohort.termdb.q.sampleName2id(e),null==a))return[];const l=await f.read_file(s.join(h.tpmasterdir,n.folder,a.toString()));return JSON.parse(l)}}}(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 a,l,c;let u=o;if(null!==(a=t.cohort)&&void 0!==a&&null!==(l=a.termdb)&&void 0!==l&&null!==(c=l.q)&&void 0!==c&&c.sampleName2id&&(u=t.cohort.termdb.q.sampleName2id(o),null==u))return[];return await G(s.join(h.tpmasterdir,n[r].folder,u.toString()),e,n[r],i)}}}(t,e),u(t),function(t){if(!t.ssm2canonicalisoform)return;if(t.ssm2canonicalisoform.gdcapi)return void r.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 J(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 J(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 J(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};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("value"in e&&(o.value=e.value),r.formatK2v)for(const t in r.formatK2v)o[t]=r.formatK2v[t];e.dt==p||e.dt==m||e.dt,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 x(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){W(t,o.byOrigin[e],n,r,e,i)}else W(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{}";Y(t,r)}else{if(!n.yes||!n.no||!n.term_id)throw"ds.assayAvailability.byDt properties require .term_id .yes{} .no{}";Y(t,n)}}}(t),null!==(a=t.cohort)&&void 0!==a&&null!==(l=a.db)&&void 0!==l&&l.refresh&&o&&N(t,o,i)}function E(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});if(t.queries.singleSampleGenomeQuantification){n.singleSampleGenomeQuantification={};for(const e in t.queries.singleSampleGenomeQuantification){const r=t.queries.singleSampleGenomeQuantification[e];n.singleSampleGenomeQuantification[e]={sample_id_key:r.sample_id_key,min:r.min,max:r.max}}}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 R(t){var e,o,i,s;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 a=t.cohort.termdb;if(null!=a&&null!==(e=a.dictionary)&&void 0!==e&&e.gdcapi)await c(t);else if(null!=a&&null!==(o=a.dictionary)&&void 0!==o&&o.dbFile)t.cohort.db={file:a.dictionary.dbFile},delete a.dictionary.dbFile,k(t);else{if(!t.cohort.db)throw"unknown method to initiate dictionary";k(t)}if(a.termid2totalsize2&&(a.termid2totalsize2.gdcapi,a.termid2totalsize2.get=async(e,n={},o=null)=>a.termid2totalsize2.gdcapi?await r.get_termlst2size(e,n,o,t):await async function(t,e,n,r){const o=new Map;for(const n of t)if(n.term&&"categorical"==n.term.type){var i,s;const t={term1_id:n.id,term1_q:{type:"values"}};e.tid2value&&(t.filter=Z(e.tid2value,r));const a=await q(t,r,r.cohort.termdb);if(null==a||null===(i=a.data)||void 0===i||null===(s=i.charts)||void 0===s||!s[0])continue;const l=[];for(const t of a.data.charts[0].serieses)l.push([t.seriesId,t.total]);o.set(n.id,l)}return n?[o,n]:o}(e,n,o,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[]"}}(a),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 I(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 I(o.file,e.PCcount)}}}}(a),await S(t),await A(t),"minTimeSinceDx"in a){if(!Number.isFinite(a.minTimeSinceDx))throw"termdb.minTimeSinceDx not number";if(a.minTimeSinceDx<=0)throw"termdb.minTimeSinceDx<=0"}if("ageEndOffset"in a){if(!Number.isFinite(a.ageEndOffset))throw"termdb.ageEndOffset not number";if(a.ageEndOffset<=0)throw"termdb.ageEndOffset<=0"}if(a.termIds){if(a.termIds.ageDxId){const t=a.q.termjsonByOneid(a.termIds.ageDxId);if(!t)throw"unknown term for termIds.ageDxId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageDxId not integer/float"}if(a.termIds.ageLastVisitId){const t=a.q.termjsonByOneid(a.termIds.ageLastVisitId);if(!t)throw"unknown term for termIds.ageLastVisitId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageLastVisitId not integer/float"}if(a.termIds.ageNdiId){const t=a.q.termjsonByOneid(a.termIds.ageNdiId);if(!t)throw"unknown term for termIds.ageNdiId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageNdiId not integer/float"}if(a.termIds.ageDeathId){const t=a.q.termjsonByOneid(a.termIds.ageDeathId);if(!t)throw"unknown term for termIds.ageDeathId";if("integer"!=t.type&&"float"!=t.type)throw"termIds.ageDeathId not integer/float"}}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(null!==(i=t.cohort)&&void 0!==i&&null!==(s=i.db)&&void 0!==s&&s.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 I(t,e){const n=new Map;for(let t=1;t<=e;t++)n.set(C+t,new Map);let r=0;for(const o of(await f.read_file(s.join(h.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=C+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 P(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 F(t,e){var n;const r=t.queries.snvindel.byrange;if(r._tk.file)await f.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 f.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=D(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 z(e,r._tk.samples,t);s&&i.push("-s",s.map((t=>t.name)).join(",")),e.variantFilter&&M(e.variantFilter,i);const a=[];return await f.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],h=i[4].split(","),p=i[5],m={pos:u-1};d(r._tk,f,h,m,p,l,e.isoform);for(const o of m.mlst){var g,y,v;e.hiddenmclass&&e.hiddenmclass.has(o.class)||(L(o,e)||m.mlst.length>1&&null!==(g=e.variantFilter)&&void 0!==g&&g.lst&&B(o,e)||(o.chr=(r._tk.nochr?"chr":"")+c,o.ssm_id=[o.chr,o.pos,o.ref,o.alt].join(T),null!==(y=r._tk)&&void 0!==y&&null!==(v=y.samples)&&void 0!==v&&v.length&&($(r,o,i,e.addFormatValues,t,s,n),!o.samples)||a.push(o)))}}}),a}}function D(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 L(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 B(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 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l,c,u,f,d;try{l=JSON.parse(s[3])}catch(t){return}if(l.dt!=m&&l.dt!=g)return;if(l.class=l.dt==g?b:v,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(T);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]:j;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 V(t,e){const n=t.queries.cnv.byrange;if(n.file)await f.validate_tabixfile(n.file);else{if(!n.url)throw"file and url both missing on cnv.byrange{}";n.dir=await f.cache_index(n.url,n.indexURL)}n.nochr=await f.tabix_is_nochr(n.file||n.url,null,e);{const t=await f.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=D(e);let o;{const r=await z(e,n.samples,t);r&&(o=new Set(r.map((t=>t.name))))}const i=[],s=[];for(const t of e.rglst)s.push(f.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==y&&Number.isFinite(c.value)&&!(c.value>0&&e.cnvGainCutoff&&c.value<e.cnvGainCutoff)&&!(c.value<0&&e.cnvLossCutoff&&c.value>e.cnvLossCutoff)&&(c.start=a,c.stop=l,c.class=c.value>0?_:w,(!e.hiddenmclass||!e.hiddenmclass.has(c.class))&&(!c.sample||!o||o.has(c.sample)))){if(c.ssm_id=[t.chr,c.start,c.stop,c.value].join(T),c.sample){const t={sample_id:c.sample};if(c.mattr){if(r)for(const t in r){const e=t 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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,u);const f=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.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)}throw"insufficient query parameters for geneCnv"}(t,e);n.geneCnv=r}!function(t,e){if(e.skewer){const n=[];for(const r of e.skewer)t.rglst&&!t.rglst.find((t=>r.chr==t.chr&&r.pos>=t.start&&r.pos<=t.stop))||n.push(r);e.skewer=n}e.genecnvAtsample}(t,n),n.mclass2variantcount=function(t){const e=new Map;for(const n of t){const t=n.class||n.dt;e.set(t,1+(e.get(t)||0))}return[...e].sort(((t,e)=>e[1]-t[1]))}(n.skewer)}return function(t,e,n){const r=new Set;if(n.skewer)for(const o of n.skewer)if(o.samples){o.occurrence=o.samples.length,a(o,t,e),l(o,e);for(const t of o.samples)r.add(t.sample_id);delete o.samples}r.size&&(n.sampleTotalNumber=r.size)}(t,e,n),n}if(t.geneExpression){if(!e.queries.geneExpression)throw"not supported";const n=await e.queries.geneExpression.get(t);if(0==n.size)throw"no data";return 1==n.size?{gene2sample2value:n}:{clustering:await c(n,t)}}throw"do not know what client wants"}(s,u);n.send(f)}catch(t){n.send({error:t.message||t}),t.stack&&console.log(t.stack)}}}function a(t,e,n){if(e.skewerRim){if("format"!=e.skewerRim.type)throw"unknown skewerRim.type";t.rim1count=0;for(const n of t.samples){var r;(null===(r=n.formatK2v)||void 0===r?void 0:r[e.skewerRim.formatKey])==e.skewerRim.rim1value&&t.rim1count++}}}function l(t,e){var n;if(null!==(n=e.queries.snvindel)&&void 0!==n&&n.format)for(const n in e.queries.snvindel.format)if(e.queries.snvindel.format[n].isFilter){t.formatK2count||(t.formatK2count={}),t.formatK2count[n]||(t.formatK2count[n]={v2c:{},unannotatedCount:0});for(const e of t.samples){var r;const o=null===(r=e.formatK2v)||void 0===r?void 0:r[n];null==o?t.formatK2count[n].unannotatedCount++:t.formatK2count[n].v2c[o]=1+(t.formatK2count[n].v2c[o]||0)}}}async function c(t,e){const n=new Set;for(const e of t.values())for(const t in e)n.add(t);const r={matrix:[],row_names:[],col_names:[...n],cluster_method:e.clusterMethod,plot_image:!1};for(const[e,n]of t){r.row_names.push(e);const t=[];for(const e of r.col_names)t.push(n[e]||0);const o=u(t);r.matrix.push(o)}const o=new Date,s=await i("cluster",JSON.stringify(r)),a=new Date;let l,c;console.log("Time taken to run rust gene clustering script:",a-o,"ms");const f=s.split("\n");for(let t of f)t.includes("colSteps")?l=JSON.parse(JSON.parse(t.replace("colSteps:",""))):t.includes("rowSteps")&&(c=JSON.parse(JSON.parse(t.replace("rowSteps:",""))));return{colSteps:l,rowSteps:c,geneNameLst:r.row_names,sampleNameLst:r.col_names,matrix:r.matrix}}function u(t){let e=0;for(const n of t)e+=n;const n=e/t.length,r=Math.sqrt(t.map((t=>(t-n)**2)).reduce(((t,e)=>t+e),0)/(t.length-1));return 0==r?t:t.map((t=>(t-n)/r))}},4143:(t,e,n)=>{"use strict";n.d(e,{R:()=>s});const{filterJoin:r}=n(478),{get_rows_by_one_key:o}=n(2852),i=n(1271).run_rust;n(1017),n(334);async function s(t,e,n,r){!function(t,e){if(!t.chr)throw"q.chr missing";if(t.start=Number(t.start),t.stop=Number(t.stop),!Number.isInteger(t.start)||!Number.isInteger(t.stop))throw"q.start/stop is not integer";if("object"!=typeof t.details)throw"q.details{} not object";if(!Array.isArray(t.details.groups))throw"q.details.groups[] not array";if(!t.details.groups[0])throw"q.details.groups[0] missing";if(t.details.groups.length>2)throw"q.details.groups[] has more than 2";for(const r of t.details.groups)if("filter"==r.type){if("object"!=typeof r.filter)throw".filter not an object for group type=filter"}else if("population"==r.type){var n;if(!r.key)throw".key missing from group type=population";if(null===(n=e.queries.snvindel)||void 0===n||!n.populations)throw"group type=population but this ds does not have populations";if(!e.queries.snvindel.populations.find((t=>t.key==r.key)))throw"invalid key of group type=population"}else{if("info"!=r.type)throw"unknown group type from details.groups[]";if(!r.infoKey)throw".infoKey missing from group type=info"}if(t.details.groupTestMethods){if(!Array.isArray(t.details.groupTestMethods))throw"details.groupTestMethods[] not array";if(!Number.isInteger(t.details.groupTestMethodsIdx))throw"details.groupTestMethodsIdx not integer";if(!t.details.groupTestMethods[t.details.groupTestMethodsIdx])throw"invalid array index of details.groupTestMethodsIdx"}}(t,n);const i=await async function(t,e){const 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 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 from groupTestMethods[]"}}(t,e,n);if("population"==r.type&&"filter"==i.type||"population"==i.type&&"filter"==r.type)return void await async function(t,e,n){const r=await async function(t,e,n){const r=e.groups.find((t=>"population"==t.type));if(!r)return;if(!r.adjust_race)return;const 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 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=n*e.get(i).average,s.ACadj=0==s.ANadj?0:s.ACraw*s.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=200*e;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:.8em">\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>${Math.floor(o[1].refCount)}</td>\n\t\t\t\t</tr>\n\t\t\t\t</table>`}]):console.log(`${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.r(e),n.d(e,{combineSamplesById:()=>d,get_crosstabCombinations:()=>g,validate_variant2samples:()=>f});const{stratinput:r}=n(1881),{querySamples_gdcapi:o}=n(5243),{get_densityplot:i}=n(9402),{ssmIdFieldsSeparator:s}=n(9535),{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,y,v,b,_,w;let e=!1;if(null!==(n=t.queries)&&void 0!==n&&null!==(f=n.snvindel)&&void 0!==f&&null!==(y=f.byrange)&&void 0!==y&&null!==(v=y._tk)&&void 0!==v&&v.samples&&(e=!0),null!==(b=t.queries)&&void 0!==b&&null!==(_=b.svfusion)&&void 0!==_&&null!==(w=_.byrange)&&void 0!==w&&w.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,y,v;return!t.useIntegerSampleId&&null!=e&&null!==(f=e.cohort)&&void 0!==f&&null!==(y=f.termdb)&&void 0!==y&&null!==(v=y.q)&&void 0!==v&&v.id2sampleName&&n.forEach((t=>t.sample_id=e.cohort.termdb.q.id2sampleName(t.sample_id))),n}if(t.get==e.variant2samples.type_sunburst)return await async function(t,e,n){var o,i;const s=r(t,n.twLst.map((t=>({k:t.id}))));for(const t of s)delete t.lst;if(null!=e&&null!==(o=e.cohort)&&void 0!==o&&null!==(i=o.termdb)&&void 0!==i&&i.termid2totalsize2){const t=await g(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}async function g(t,e,n,r){var o,i;if(0==t.length)throw"zero terms for crosstab";if(t.length>3)throw"crosstab will not work with more than 3 levels";const s=[],a=new Map;for(const e of t)a.set(e.id,new Set);const l=!r;if(r)for(const n of 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 n=await e.cohort.termdb.termid2totalsize2.get([t[0]]);for(const[t,r]of n.get(c)){const n=e.cohort.termdb.useLower?t.toLowerCase():t;l?(a.get(c).add(n),s.push({count:r,id0:c,v0:n})):a.get(c).has(n)&&s.push({count:r,id0:c,v0:n})}}const 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"),r.push(e.stop));const o=t.isnot?"NOT ":"";n.length&&i.push(o+"("+n.join(" AND ")+")")}a&&o.values&&(s=Object.keys(o.values).filter((t=>o.values[t].uncomputable)).map(Number).filter((e=>t.isnot||!t.ranges.find((t=>"value"in t&&Number(t.value)==e)))),s.length&&r.push(...s));const l=i.join(" OR ");return{CTEs:[`\n\t\t    ${e} AS (\n\t\t\t\tSELECT sample\n\t\t\t\tFROM anno_${o.type}\n\t\t\t\tWHERE term_id = ?\n\t\t\t\t${l?"AND ("+l+")":""}\n\t\t\t\t${s&&s.length?`AND value NOT IN (${s.map((t=>"?")).join(",")})`:""}\n\t\t\t)`],values:r,CTEname:e}}function s(t,e){let n,r;if(t.bar_by_children)n="child";else{if(!t.bar_by_grade)throw"must set the bar_by_grade or bar_by_children query parameter";n="grade"}if(t.value_by_max_grade)r="max_grade";else if(t.value_by_most_recent)r="most_recent";else{if(!t.value_by_computable_grade)throw"unknown setting of value_by_?";r="computable_grade"}const o=[],i=[];if(!t.values)throw t.grade_and_child?"-- Todo: tvs.grade_and_child":'unknown condition term filter type: expecting term-value "values" or "grade_and_child" key';return i.push(t.term.id,n,...t.values.map((t=>""+t.key))),o.push(`\n\t\t\t${e} AS (\n\t\t\t\tSELECT sample\n\t\t\t\tFROM precomputed\n\t\t\t\tWHERE term_id = ? \n\t\t\t\tAND value_for = ? \n\t\t\t\tAND ${r} = 1\n\t\t\t\tAND value ${t.isnot?"NOT":""} IN (${t.values.map((t=>"?")).join(", ")})\n\t\t\t)`),{CTEs:o,values:i,CTEname:e}}e.getFilterCTEs=async function t(e,a,l="f"){if(!e)return;if("tvslst"!=e.type)throw'filter.type is not "tvslst" but: '+e.type;if(!Array.isArray(e.lst))throw"filter.lst must be an array";if(0==e.lst.length)return console.error("filter.lst[] is zero length, see if is an error");if(1==e.lst.length){if("tvslst"==e.lst[0].type)throw'only one element at a level: type should not be "tvslst"'}else if("or"!=e.join&&"and"!=e.join)throw'multiple elements at a level: filter.join must equal either "or" or "and"';"in"in e||(e.in=!0);const c=[],u=[],f=[];for(const[d,h]of e.lst.entries()){const e=l+"_"+d;let p;if("tvslst"==h.type)p=await t(h,a,e);else if("categorical"==h.tvs.term.type)p=n(h.tvs,e);else if("samplelst"==h.tvs.term.type)p=r(h.tvs,e);else if("integer"==h.tvs.term.type||"float"==h.tvs.term.type)p=i(h.tvs,e,a);else if("condition"==h.tvs.term.type)p=s(h.tvs,e);else{if("geneVariant"!=h.tvs.term.type)throw"unknown term type";p=await o(h.tvs,e,a)}c.push(p.CTEname),u.push(...p.CTEs),f.push(...p.values)}const d="and"==e.join?"INTERSECT":"UNION",h=c.map((t=>"SELECT * FROM "+t)).join("\n"+d+"\n");return e.in?u.push(`\n\t\t\t\t${l} AS (\n\t\t\t\t\t${h}\n\t\t\t\t)\n\t\t\t`):u.push(`\n\t\t\t\t${l} AS (\n\t\t\t\t\tSELECT id as sample\n\t\t\t\t\tFROM sampleidmap\n\t\t\t\t\tWHERE sample NOT IN (\n\t\t\t\t\t\t${h}\n\t\t\t\t\t)\n\t\t\t\t)\n\t\t\t`),{filters:u.join(",\n"),CTEs:u,values:f,CTEname:l}}},1778:(t,e,n)=>{"use strict";n.r(e),n.d(e,{initGDCdictionary:()=>d});const r=n(6452),o=n(1017),i=n(1575).isUsableTerm,s=n(334),a=process.env.PP_GDC_HOST||"https://api.gdc.cancer.gov",l=a+(a.includes("/v0")?"":"/v0")+"/graphql",c=o.join(a,"ssm_occurrences/_mapping"),u={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}}},f={};async function d(t){const e=new Map,n=await r(c,{method:"GET",headers:{"Content-Type":"application/json",Accept:"application/json"}});let d;try{d=JSON.parse(n.body)}catch(t){throw"invalid JSON from GDC dictionary"}if(!d._mapping)throw"returned data does not have ._mapping";if(!Array.isArray(d.fields))throw".fields not array";if(!Array.isArray(d.nested))throw".nested not array";const g=new Set(d.nested);let y=0,v=0,b=0,_=0,w=0,x=0;for(const t of d.fields){if((k=t).startsWith("ssm")||k.startsWith("case.observation")||k.startsWith("case.available_variation_data")){y++;continue}const n=t.split(".");for(let t=1;t<n.length;t++){const r=n.slice(0,t).join("."),o=r+"."+n[t],i={id:o.toLowerCase(),name:n[t][0].toUpperCase()+n[t].slice(1).replace(/_/g," "),included_types_set:new Set,child_types_set:new Set};if(t==n.length-1){i.isleaf=!0;const t=d._mapping["ssm_occurrence_centrics."+o];t&&("keyword"==t.type?(i.type="categorical",b++):"long"==t.type?(i.type="integer",i.bins=f[i.id]||JSON.parse(JSON.stringify(u)),_++):"double"==t.type&&(i.type="float",i.bins=f[i.id]||JSON.parse(JSON.stringify(u)),w++)),i.type||v++,h(i)}if(1==t);else if(i.parent_id=r,i.type){i.included_types_set.add(i.type);let t=e.get(r);for(;t&&(t.included_types_set.add(i.type),t.child_types_set.add(i.type),t.parent_id);)t=e.get(t.parent_id)}g.has(o)&&(i.isObjectList=!0),e.set(o,i)}}var k;for(const t of e.values())t.type||x++,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,",y,"lines skipped,",v,"lines with unknown term type,","categorical="+b,"integer="+_,"float="+w,"parent="+x),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,s=null,a=null)=>{(t=t.toLowerCase()).includes(" ")&&(t=t.replace(/\s/g,"_"));const l=[];for(const n of e.values())a&&!i(n,a)||n.id.includes(t)&&l.push(JSON.parse(JSON.stringify(n)));return await r(l,s),l},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=[],b&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"categorical"}),_&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"integer"}),w&&t.cohort.termdb.termtypeByCohort.push({cohort:"",type:"float"}),await async function(t){var e,n,i;const s={"Content-Type":"application/json",Accept:"application/json"},l={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},c=await r(o.join(a,"files"),{method:"POST",headers:s,body:JSON.stringify(l)}),u=JSON.parse(c.body);if(t.gdcOpenProjects=new Set,null!=u&&null!==(e=u.data)&&void 0!==e&&null!==(n=e.aggregations)&&void 0!==n&&null!==(i=n["cases.project.project_id"])&&void 0!==i&&i.buckets){for(const e of u.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 p(a+"/ssms"),await p(a+"/ssm_occurrences"),await p(a+"/cases"),await p(a+"/files"),await p(a+"/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 r.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")}(l)}catch(t){console.error(`\n##########################################\n#\n#   GDC API unavailable\n#   ${a}\n#   ${l}\n#\n##########################################`)}}(),async function(t){try{if(t.aliquot2submitter={cache:new Map,get:async e=>t.aliquot2submitter.cache.has(e)?t.aliquot2submitter.cache.get(e):e},s.features.stopGdcCacheAliquot)return console.log("GDC aliquot2submitter not cached!");const e=await m(t,1,0);if(!Number.isInteger(e))throw"gdc totalCases not integer";const n=new Date;console.log("Start to cache aliquot IDs of",e,"cases...");const r=1e3;for(let n=0;n<Math.ceil(e/r);n++)await m(t,r,1e3*n);console.log("Done caching",t.aliquot2submitter.cache.size,"aliquot IDs.",new Date-n,"ms")}catch(t){console.log("Error at caching: "+t)}}(t)}function h(t){"case.diagnoses.age_at_diagnosis"!=t.id||(t.printDays2years=!0)}async function p(t){try{const e=new Date;await r(t),console.log("GDC API okay: "+t,new Date-e,"ms")}catch(e){throw"gdc api down: "+t}}async function m(t,e,n,o){var i,s,l;const c=["fields=samples.portions.analytes.aliquots.aliquot_id,samples.submitter_id"];if(o)c.push('filters={"op":"and","content":[{"op":"=","content":{"field":"samples.portions.analytes.aliquots.aliquot_id","value":["'+o+'"]}}]}');else{if(!Number.isInteger(e)||!Number.isInteger(n))throw"size and from not integers";c.push("size="+e),c.push("from="+n)}const u=await r(a+"/cases?"+c.join("&")),f=JSON.parse(u.body);if(!Array.isArray(null==f||null===(i=f.data)||void 0===i?void 0:i.hits))throw"re.data.hits[] not array";for(const e of f.data.hits)if(Array.isArray(e.samples))for(const n of e.samples){const e=n.submitter_id;if(Array.isArray(n.portions))for(const r of n.portions)if(Array.isArray(r.analytes))for(const n of r.analytes)if(Array.isArray(n.aliquots))for(const r of n.aliquots){const n=r.aliquot_id;if(!n)throw"aliquot.aliquot_id missing";t.aliquot2submitter.cache.set(n,e)}}return null===(s=f.data)||void 0===s||null===(l=s.pagination)||void 0===l?void 0:l.total}},7860:(t,e,n)=>{"use strict";n.r(e),n.d(e,{copy_term:()=>N,handle_request_closure:()=>q});var r=n(5684),o=n(7027),i=n(3856),s=n(6191),a=n.n(s),l=n(4065);const c=n(5174),u=n(2852),f=n(5708),d=n(4453),h=n(1468),p=n(8599),m=n(3795),g=n(1711).getOrderedLabels,y=n(1575).isUsableTerm,v=n(2188).uR,b=n(2188).v8,_=n(9936).g,w=n(2974).getData,x=n(601).v,k=n(4143).R;function q(t){return async(e,n)=>{const s=e.query;try{const q=t[s.genome];if(!q)throw"invalid genome";const[A,M]=function(t,e){{const r=t.datasets[e.dslabel];if(r){var n;if(null!=r&&null!==(n=r.cohort)&&void 0!==n&&n.termdb)return[r,r.cohort.termdb];throw".cohort.termdb not found on this dataset"}}if(!t.termdbs)throw"genome-level termdb not available";const r=t.termdbs[e.dslabel];if(!r)throw"invalid dslabel";if(!r.cohort)throw"ds.cohort missing for genome-level termdb";if(!r.cohort.termdb)throw"ds.cohort.termdb{} missing for a genome-level termdb";return[r,r.cohort.termdb]}(q,s);if(s.gettermbyid)return function(t,e,n){const r=n.q.termjsonByOneid(t.gettermbyid);e.send({term:r?N(r):void 0})}(s,n,M);if(s.getcategories)return await async function(t,e,n,r,o){var i,s,a;if(!t.tid)throw".tid missing";const l="geneVariant"==t.type?{name:t.tid,type:"geneVariant",isleaf:!0}:n.q.termjsonByOneid(t.tid),c={filter:t.filter,terms:"geneVariant"==t.type?[{term:l,q:{isAtomic:!0}}]:[{id:t.tid,term:l,q:t.term1_q||S(l,t)}],currentGeneNames:t.currentGeneNames},u=await w(c,r,o);if(u.error)throw u.error;const f=[];if("geneVariant"==t.type){var d;const e=u.samples,n=new Map;if(null!==(d=r.assayAvailability)&&void 0!==d&&d.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)f.push({dt:t,classes:e})}else{const e=new Map;for(const n in u.samples){const r=u.samples[n][t.tid];r&&("key"in r&&e.set(r.key,1+(e.get(r.key)||0)))}for(const[t,n]of e){var h,p;f.push({samplecount:n,key:t,label:(null==l||null===(h=l.values)||void 0===h||null===(p=h[t])||void 0===p?void 0:p.label)||t})}}const m=g(l,(null===(i=u.refs)||void 0===i||null===(s=i.byTermId)||void 0===s||null===(a=s[t.tid])||void 0===a?void 0:a.bins)||[]);m.length&&f.sort(((t,e)=>m.indexOf(t.label)-m.indexOf(e.label)));e.send({lst:f,orderedLabels:m})}(s,n,M,A,q);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 u.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,A);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 u.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 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,A);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,M,A);if(s.getconditioncategories)return await async function(t,e,n,r){if(!t.tid)throw".tid missing";const o=n.q.termjsonByOneid(t.tid),i={ds:r,term1_id:t.tid,term1_q:t.term1_q||S(o,t)};t.filter&&(i.filter=t.filter);const s=await u.get_summary_conditioncategories(i),a=s.CTE1.bins?s.CTE1.bins:[];e.send({lst:s.lst,orderedLabels:g(o,a)})}(s,n,M,A);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,M);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(N)})}(s,n,M);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,10,t.cohortStr,t.treeFilter,t.usecase,s);u.push(...f.map(N));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,M,A,q);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,M);if(s.phewas)return s.update?await f.update_image(s,n):s.getgroup?await f.getgroup(s,n):await f.trigger(s,n,A);if(s.gettermdbconfig)return c.make(s,n,A,q);if(s.getcohortsamplecount)return n.send({count:A.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,A));if(s.getsamples)return await async function(t,e,n){const r=(await u.get_samples(t.filter,n)).map((t=>n.cohort.termdb.q.id2sampleName(t)));e.send({samples:r})}(s,n,A);if(s.getcuminc)return await async function(t,e,n){if(!t.minSampleSize)throw"missing minSampleSize";t.minSampleSize=Number(t.minSampleSize);const r=await d.get_incidence(t,n);e.send(r)}(s,n,A);if(s.getsurvival)return await async function(t,e,n){const r=await h.get_survival(t,n);e.send(r)}(s,n,A);if(s.getregression)return await async function(t,e,n){const r=await p.get_regression(t,n);e.send(r)}(s,n,A);if(s.validateSnps)return n.send(await m.validate(s,M,A,q));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,A);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,A,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,M);if(s.getSampleScatter)return await v(e,s,n,A,q);if(s.getLowessCurve)return await b(e,s,n);if(s.getCohortsData)return await x(s,n,A);if(s.getViolinPlotData)return await _(s,n,A,q);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,A);if("termTypes"==s.for)return n.send(await A.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,A,q);if("mds3variantData"==s.for)return await k(s,n,A,q);throw s.for,"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 N(t){return JSON.parse(JSON.stringify(t))}function S(t,e){if("categorical"==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={filter: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};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 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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);for(const{sample:t,term_id:e,key:r,value:i}of f){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 from one of matrixplots.plots[]";if(!e.file)throw"unknown data source of one of matrixplots.plots[]";{const t=await c.read_file(r.join(l.tpmasterdir,e.file));e.matrixConfig=JSON.parse(t),e.getConfig&&(e.matrixConfig=e.getConfig(e.matrixConfig))}}}}},5708:(t,e,n)=>{"use strict";n.r(e),n.d(e,{do_precompute:()=>h,getgroup:()=>w,trigger:()=>d,update_image:()=>v});const r=n(7147),o=n(1017),i=n(3856),s=n(2852),a=n(6718).createCanvas,l=n(7860),c=n(4521),u=n(334),f=n(9157);async function d(t,e,n){if(!n.cohort)throw"ds.cohort missing";if(!n.cohort.termdb)throw"cohort.termdb missing";if(!n.cohort.termdb.phewas)throw"not allowed on this dataset";if(!t.ssid)throw"ssid missing";const r={};let a;t.filter&&(a=new Set(await s.get_samples(t.filter,n)));const[c,d]=await i.loadfile_ssid(t.ssid,a);r.numberofsamples=c.size;const 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 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c)console.log(t.group1lst.length+(t.group2lst?"/"+t.group2lst.length:"")+"\t"+t.group1label+"\t"+o.name);n.push(r+"\t"+o.id+"\t"+i+"\t"+(l.term1_q?JSON.stringify(l.term1_q):"{}")+"\t"+JSON.stringify(c))}}r.writeFileSync("category2vcfsample",n.join("\n")),console.log('Phewas precompute result written to file "category2vcfsample".')}(t)}function p(t){const{categories:e,q:n,term:r,subcohortTermtype2samples:o,condition_samplelst:i}=t;if(o&&o[n.cohortname]&&o[n.cohortname].termtype&&o[n.cohortname].termtype[r.type]){const t=o[n.cohortname].termtype[r.type].samples;for(const n of e)if(n.group2lst)n.group2lst=n.group2lst.filter((e=>-1!=t.indexOf(e)));else if(n.copycontrolfrom1stgroup){n.group2lst=[];for(const t of e[0].group2lst)n.group2lst.push(t)}else{const e=new Set(n.group1lst);n.group2lst=t.filter((t=>!e.has(t)))}return e}if(i&&"condition"==r.type){for(const t of e)if(t.group2lst)t.group2lst=t.group2lst.filter((t=>-1!=i.indexOf(t)));else 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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;c.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;c.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;c.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;c.getTermParent=e=>{if(t.has(e))return t.get(e);const 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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(","):[],s&&!i(o,s).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;c.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;c.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=? AND t.id=a.ancestor_id"),e=new Map;c.getAncestorNames=n=>{if(e.has(n))return e.get(n);const r=t.all(n).map((t=>t.name));return e.set(n,r),r}}{const t={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=?")},e={categorical:n.prepare("SELECT value FROM anno_categorical WHERE term_id=? AND sample=?"),integer:n.prepare("SELECT value FROM anno_integer WHERE term_id=? AND sample=?"),float:n.prepare("SELECT value FROM anno_float WHERE term_id=? AND sample=?")},r={categorical:n.prepare("SELECT value FROM anno_categorical a,sampleidmap s WHERE term_id=? AND s.name=?"),integer:n.prepare("SELECT value FROM anno_integer a,sampleidmap s WHERE term_id=? AND s.name=?"),float:n.prepare("SELECT value FROM anno_float a, sampleidmap s WHERE term_id=? 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0!==a&&a.draftChartTypes&&i[n.cohort].add(...r.features.draftChartTypes),"survival"!=n.type||i[n.cohort].has("survival")||i[n.cohort].add("survival"),"condition"!=n.type||i[n.cohort].has("cuminc")||i[n.cohort].add("cuminc"),"float"!=n.type&&"integer"!=n.type||(s[n.cohort]+=n.samplecount)}}for(const t in i)i[t]=[...i[t]];if(t.cohort.allowedChartTypes)for(const e in i)i[e]=i[e].filter((e=>t.cohort.allowedChartTypes.includes(e)));if(t.queries){if(t.queries.snvindel||t.queries.trackLst)for(const t in i)i[t].push("genomeBrowser");if(t.queries.geneExpression)for(const t in i)i[t].push("geneExpression")}return i}}function a(t){const e=t.prepare("SELECT name FROM sqlite_master WHERE type='table'").all();return new Set(e.map((t=>t.name)))}function l(t){var e,n;if(t.cohort.termdb.termtypeByCohort){if(!Array.isArray(t.cohort.termdb.termtypeByCohort))throw"termtypeByCohort is not array"}else{if(null===(e=t.cohort)||void 0===e||null===(n=e.db)||void 0===n||!n.connection)throw"termtypeByCohort[] not set but cohort.db.connection missing";t.cohort.termdb.termtypeByCohort=t.cohort.db.connection.prepare("WITH c AS (\n\t\t\tSELECT cohort, term_id\n\t\t\tFROM subcohort_terms s\n\t\t\tGROUP BY cohort, term_id\n\t\t) \n\t\tSELECT cohort, type, count(*) as samplecount\n\t\tFROM terms t\n\t\tJOIN c ON c.term_id = t.id\n\t\tGROUP BY cohort, type").all()}}},3795:(t,e,n)=>{"use strict";n.r(e),n.d(e,{add_bcf_variant_filter:()=>h,validate:()=>d});const r=n(7147),o=n(1017),i=n(3856),s=n(2852),a=(n(7860),n(4521),n(334)),{compute_mclass:l}=n(3625),c="%CHROM\t%POS\t%REF\t%ALT[\t%TGT]\n",u="%POS\t%ID\t%REF\t%ALT\t%INFO[\t%TGT]\n",f=".";async function d(t,e,n,d){try{if(t.sumSamples)return await async function(t,e,n,r){if(!t.cacheid)throw"cacheid missing";if(a.cache_snpgt.fileNameRegexp.test(t.cacheid))throw"invalid cacheid";let l,c;if(n.track){if(l=n.track.vcf,!l)throw"ds.track.vcf missing"}else 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 f;if(s.chr2files){if(e=null===(f=s.chr2files)||void 0===f?void 0:f[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 d=o.join(a.cachedir,await i.write_tmpfile(u.join("\n"))),h=o.join(a.cachedir,await i.write_tmpfile([...l].join("\n")));await i.get_lines_bigfile({isbcf:!0,args:["query","-R",d,"-f",c,"-v",h],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]?"":n[t])}}}),r.unlink(d,(()=>{})),r.unlink(h,(()=>{}));const p=["snpid\tchr\tpos\tref\talt\teff\t"+s.samples.map((t=>t.name)).join("\t")];for(const t of e)t.invalid||t.gtlst&&(p.push(t.snpid+"\t"+t.chr+"\t"+t.pos+"\t"+t.referenceAllele+"\t"+t.altAlleles.join(",")+"\t"+(t.effectAllele||"")+"\t"+t.gtlst.join("\t")),delete t.gtlst);const m=t.genome+"_"+t.dslabel+"_"+new Date/1+"_"+Math.ceil(1e4*Math.random());return await i.write_file(o.join(a.cache_snpgt.dir,m),p.join("\n")),m}(t,s,e);return{snps:s,cacheid:l}}(t,n,d);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,d;if(e.track){if(c=e.track.vcf,!c)throw"ds.track.vcf missing";if(d=c.chr2bcffile[t.chr],!d)throw"chr not in chr2bcffile"}else{var p;if(c=e.queries.snvindel.byrange._tk,c.chr2files)d=null===(p=c.chr2files)||void 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getCTE(t,e,n,r,o,s){if(!s.groups)throw`.groups[] missing from a group-set, term.id='${e.id}'`;const a=[],l=[];for(const t of s.groups)if("values"==t.type)a.push(`SELECT sample, ? as key, value\n\t\t\t\t\tFROM anno_categorical a\n\t\t\t\t\tWHERE term_id=?\n\t\t\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t\t\t`),o.push(t.name,e.id,...t.values.map((t=>t.key.toString())));else{if("filter"!=t.type)throw`unsupported groupset type='${t.type}'`;if(!("activeCohort"in r.groupsetting)||!t.filter4activeCohort)throw`activeCohort error: cannot construct filter statement for group name='${t.name}', term.id=${e.id}`;{const s=t.filter4activeCohort[r.groupsetting.activeCohort],c=await getFilterCTEs(s,n,"xf"+i++);if(!c)throw`unable to construct a group='${t.name}' filter for term.id='${e.id}'`;l.push(c.filters),o.push(...c.values.slice(),t.name,t.name),a.push(`SELECT sample, ? AS key, ? AS value\n\t\t\t\t\t\tFROM ${c.CTEname}`)}}return{sql:`${l.length?l.join("\n,")+",":""}\n\t\t\t${t} AS (\n\t\t\t\t${a.join("\nUNION ALL\n")}\n\t\t\t)`,tablename:t}}}},6759:(t,e,n)=>{"use strict";function r(t){const e=t.cohort.db.connection.prepare("select * from features").all();return{cohorts:t.cohort.db.connection.prepare("select * from cohorts where cohort in (select distinct(cohort) from cohort_features)\n\t\t order by sample_count desc").all(),features:e,cfeatures:t.cohort.db.connection.prepare("select * from cohort_features").all()}}n.r(e),n.d(e,{getCohortsData:()=>r})},9723:(t,e,n)=>{"use strict";n.r(e),n.d(e,{binary:()=>i,discrete:()=>o,time2event:()=>s});var r=n(2852);const o={getCTE(t,e,n,o,i){if(o.breaks&&o.breaks.length>0)return l(t,e,o,i);{const[n,s]=a(o);i.push(e.id,n);const l=(0,r.getUncomputableClause)(e,o);return i.push(...l.values),{sql:`${t} AS (\n\t\t\t\t\tSELECT\n\t\t\t\t\t\tsample,\n\t\t\t\t\t\t${"grade"==n?"CAST(value AS integer) as key":"value as key"},\n\t\t\t\t\t\t${"grade"==n?"CAST(value AS integer) as value":"value"}\n\t\t\t\t\tFROM\n\t\t\t\t\t\tprecomputed\n\t\t\t\t\tWHERE\n\t\t\t\t\t\tterm_id = ?\n\t\t\t\t\t\tAND value_for = ?\n\t\t\t\t\t\tAND ${s} = 1\n\t\t\t\t\t\t${l.clause}\n\t\t\t\t)`,tablename:t}}}},i={getCTE(t,e,n,r,o){if(!r.breaks)throw"binary mode requires breaks";if(1!=r.breaks.length)throw"binary mode requires one break";return l(t,e,r,o)}},s={getCTE(t,e,n,r,o){if(!r.breaks||1!=r.breaks.length)throw"one break is required";const{ageDxId:i,ageLastVisitId:s,ageNdiId:a,ageDeathId:l}=n.cohort.termdb.termIds;if(!(i&&s&&a&&l))throw"missing age terms ids";const c=`ageDx AS (\n\t\t\tSELECT sample, ROUND(value,2) AS value\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(i).type}\n\t\t\tWHERE term_id = ?\n\t\t)`;o.push(i);const u=`ageLastVisit AS (\n\t\t\tSELECT sample, ROUND(value,2) AS value\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(s).type}\n\t\t\tWHERE term_id = ?\n\t\t)`;o.push(s);const f=`ageNdi AS (\n\t\t\tSELECT sample, ROUND(value,2) AS value\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(a).type}\n\t\t\tWHERE term_id = ?\n\t\t)`;o.push(a);const d=`dead AS (\n\t\t\tSELECT anno.sample, ageDx.value AS ageDx, ageNdi.value AS ageNdi, ROUND(anno.value,2) AS ageDeath\n\t\t\tFROM ${"anno_"+n.cohort.termdb.q.termjsonByOneid(l).type} anno\n\t\t\tJOIN ageNdi ON anno.sample = ageNdi.sample\n\t\t\tJOIN ageDx ON anno.sample = ageDx.sample\n\t\t\tWHERE anno.term_id = ?\n\t\t)`;o.push(l);let h;h=e.isleaf?"eventTerms AS (\n\t\t\t\tSELECT term_id\n\t\t\t\tFROM chronicevents\n\t\t\t\tWHERE term_id = ?\n\t\t\t)":"parentTerms AS (\n\t\t\t\t\tSELECT distinct(ancestor_id) \n\t\t\t\t\tFROM ancestry\n\t\t\t\t),\n\t\t\t\teventTerms AS (\n\t\t\t\t\tSELECT a.term_id \n\t\t\t\t\tFROM ancestry a\n\t\t\t\t\tJOIN terms t ON t.id = a.term_id AND t.id NOT IN parentTerms \n\t\t\t\t\tWHERE a.ancestor_id = ?\n\t\t\t\t)",o.push(e.id);o.push(r.breaks[0]);return{sql:`${c},\n\t\t\t${u},\n\t\t\t${f},\n\t\t\t${d},\n\t\t\ttimeToEvent AS (\n\t\t\tSELECT c.*, ageDx.value AS ageDx, ageLastVisit.value AS ageLastVisit, ageNdi.value AS ageNdi\n\t\t\tFROM chronicevents c\n\t\t\tJOIN ageDx ON c.sample = ageDx.sample\n\t\t\tJOIN ageLastVisit ON c.sample = ageLastVisit.sample\n\t\t\tJOIN ageNdi ON c.sample = ageNdi.sample\n\t\t\tWHERE c.years_to_event > 0\n\t\t\tAND c.grade <= 5\n\t\t),\n\t\t\t${h},\n\t\t\tevent1 AS (\n\t\t\tSELECT sample, 1 AS key, json_object('age_dx', ageDx, 'age_event', MIN(age_graded)) AS value\n\t\t\tFROM timeToEvent\n\t\t\tWHERE term_id IN eventTerms\n\t\t\tAND (\n\t\t\t\t(grade >= ? AND age_graded <= ageLastVisit)\n\t\t\t\tOR\n\t\t\t\t(grade = 5 AND age_graded <= ageNdi)\n\t\t\t)\n\t\t\tGROUP BY sample\n\t\t),\n\t\t\tevent1samples AS (\n\t\t\tSELECT sample\n\t\t\tFROM event1\n\t\t),\n\t\t\tevent2 AS (\n\t\t\tSELECT sample, 2 AS key, json_object('age_dx', ageDx, 'age_event', ageDeath) AS value\n\t\t\tFROM dead\n\t\t\tWHERE ageDeath <= ageNdi\n\t\t\tAND sample NOT IN event1samples\n\t\t),\n\t\t\tevent2samples AS (\n\t\t\tSELECT sample\n\t\t\tFROM event2\n\t\t),\n\t\t\tevent0 AS (\n\t\t\tSELECT DISTINCT sample, 0 AS key, json_object('age_dx', ageDx, 'age_event', ageLastVisit) AS value\n\t\t\tFROM timeToEvent\n\t\t\tWHERE sample NOT IN event1samples\n\t\t\tAND sample NOT IN event2samples\n\t\t),\n\t\t\t${t} AS (\n\t\t\t\tSELECT * FROM event1\n\t\t\t\tUNION ALL\n\t\t\t\tSELECT * FROM event2\n\t\t\t\tUNION ALL\n\t\t\t\tSELECT * FROM event0\n\t\t\t)`,tablename:t}}};function a(t){const e=t.bar_by_children?"child":t.bar_by_grade?"grade":"";if(!e)throw"must set the bar_by_grade or bar_by_children query parameter";const n=t.value_by_max_grade?"max_grade":t.value_by_most_recent?"most_recent":t.value_by_computable_grade?"computable_grade":"";if(!n)throw"must set a valid value_by_*";return[e,n]}function l(t,e,n,r){const o=n.breaks,i=Object.keys(e.values).map(Number).sort(((t,e)=>t-e)),s=[];let l,c={values:[]};for(const t of i)o.includes(t)?(l=t,0===s.length?c.name="Grade < "+l:c.name=c.name+" < "+l,s.push(c),c={name:l+" =< Grade",values:[t]}):c.values.push(t);if(c.name="Grade >= "+l,s.push(c),n.groupNames&&n.groupNames.length>0)for(const[t,e]of n.groupNames.entries())s[t].name=e;const[u,f]=a(n),d=[];for(const t of s)d.push(`SELECT sample, ? as key, value\n\t\t\tFROM precomputed a\n\t\t\tWHERE\n\t\t\t\tterm_id=?\n\t\t\t\tAND value_for=?\n\t\t\t\tAND ${f}=1\n\t\t\t\tAND value IN (${t.values.map((t=>"?")).join(",")})\n\t\t`),r.push(t.name,e.id,u,...t.values.map((t=>t.toString())));return{sql:`${t} AS (\n\t\t\t${d.join("\nUNION ALL\n")}\n\t\t)`,tablename:t}}},2852:(t,e,n)=>{"use strict";n.r(e),n.d(e,{getUncomputableClause:()=>b,get_bins:()=>w,get_numericMinMaxPct:()=>k,get_numericsummary:()=>x,get_rows:()=>m,get_rows_by_one_key:()=>p,get_samplecount:()=>f,get_samples:()=>u,get_summary:()=>y,get_summary_conditioncategories:()=>h,get_summary_numericcategories:()=>d,get_term_cte:()=>g,interpolateSqlValues:()=>q});const r=n(9699),o=n(3594),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 (${o.join(",")})\n\t\tGROUP BY value`;return t.ds.cohort.db.connection.prepare(s).all(r)}async function h(t){let e;if(t.term1_q&&"cox"==t.term1_q.mode){e=await m(t,{withCTEs:!0});const n=t.ds.cohort.termdb.minTimeSinceDx;if(!n)throw"missing min time since dx";const r=new Map;for(const t of e.lst){let e;e=2===t.key1?0:t.key1;const{age_dx:o,age_event:i}=JSON.parse(t.val1);i-(o+n)<0&&(e=-1);const s=r.get(e);s?r.set(e,s+1):r.set(e,1)}const o=[];for(const[t,e]of r)o.push({key1:t,samplecount:e});e.lst=o}else e=await m(t,{withCTEs:!0,groupby:"key1"});const n=[0,1,2],r={};for(const o of n)r[o]=v(t,o,e);for(const t of e.lst)for(const e of n)r[e](t);return e}async function p(t){if(!t.key)throw".key missing";if(!t.ds)throw".ds{} missing";const e=await i(t.filter,t.ds),n=e?e.values.slice():[],r=t.ds.cohort.termdb.q.termjsonByOneid(t.key);n.push(t.key);const o=`\n\t\t${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 m(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 g(t,o,0,r),a=await g(t,o,1,r),l=await g(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",q(u,o)),t}}async function g(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 found 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e.lst)for(const e of n)r[e](t);return e}function v(t,e,n){const r="key"+e,o="val"+e,i=t=>{delete t[r],delete t[o]},s=t["term"+e+"_id"];if(!s)return i;const a=t.ds.cohort.termdb.q.termjsonByOneid(s);if(!a)return i;const l=1!=e||t.term0_id||t.term2_id?r:"key",c=1!=e||t.term0_id||t.term2_id?r:"label";if("integer"==a.type||"float"==a.type){const i=n["CTE"+e],s="range"+(1!=e||t.term0_id||t.term2_id?e:"");return t=>{t[s]=i.name2bin.get(t[r]),t[c]=t[r],delete t[o],l!==r&&(t[l]=t[r],delete t[r])}}{const n=t["term"+e+"_q"];return e=>{e[c]=function(t,e,n,r){if("categorical"==e.type)return e.values&&t in e.values?e.values[t].label:t;if("condition"==e.type){var o;if(0==(null===(o=n.breaks)||void 0===o?void 0:o.length)){if(!(t in e.values))throw`unknown grade='${t}'`;return e.values[t].label}return"cox"==n.mode?-1===t?"Event before entry into the cohort":n.groupNames[t]:t}if(e.values)return t in e.values?e.values[t].label:t;if("integer"==e.type||"float"==e.type)throw"should not work for numeric term";throw"unknown term type"}(e[r],a,n,t.ds),delete e[o],l!==r&&(e[l]=e[r],delete e[r])}}}function b(t,e,n=""){if(!t.values||!e.computableValuesOnly)return{values:[],clause:""};const r=Object.keys(t.values).filter((e=>t.values[e].uncomputable)),o=n?`${n}.value`:"value";return{values:r,clause:r.length?`AND ${o} NOT IN (${r.map((()=>"?")).join(",")})`:""}}function _(t,e){if(e.groupsetting&&!e.groupsetting.disabled&&e.groupsetting.inuse){if(Number.isInteger(e.groupsetting.predefined_groupset_idx)){if(e.groupsetting.predefined_groupset_idx<0)throw"q.predefined_groupset_idx out of bound";if(!t.groupsetting)throw"term.groupsetting missing when q.predefined_groupset_idx in use";if(!t.groupsetting.lst)throw"term.groupsetting.lst missing when q.predefined_groupset_idx in use";const n=t.groupsetting.lst[e.groupsetting.predefined_groupset_idx];if(!n)throw"q.predefined_groupset_idx out of bound";return n}if(e.groupsetting.customset)return e.groupsetting.customset;throw"do not know how to get groupset"}}function w(t,e,n,r,i){if("continuous"!=t.mode&&"spline"!=t.mode)return o.compute_bins(t,(t=>k(n,e,i,t)))}async function x(t,e,n,o=!1){const s="string"==typeof t.filter?JSON.parse(decodeURIComponent(t.filter)):t.filter;"integer"!=e.type&&"float"!=e.type||a.lst.find((t=>t.term.id==e.id&&"ranges"in t))||a.lst.push({type:"tvs",tvs:{term:e,ranges:w(t,e,n)}});const a=await i(s,n),l=[];a&&l.push(...a.values);const c=e.values?Object.keys(e.values).filter((t=>e.values[t].uncomputable)):[],u=`${a?"WITH "+a.filters+" ":""}\n\t\tSELECT value\n\t\tFROM anno_${e.type}\n\t\tWHERE\n\t\t${a?"sample IN "+a.CTEname+" AND ":""}\n\t\tterm_id=?\n\t\t${c.length?"AND value NOT IN ("+c.join(",")+")":""}`;l.push(e.id);const f=n.cohort.db.connection.prepare(u).all(l);if(!f.length)return null;f.sort(((t,e)=>t.value-e.value));const d=r.boxplot_getvalue(f);d.mean=f.length?f.reduce(((t,e)=>t+e.value),0)/f.length:0;let h=0;for(const t of f)h+=Math.pow(t.value-d.mean,2);return 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Array(3).concat("e0ecf49ebcda8856a7","edf8fbb3cde38c96c688419d","edf8fbb3cde38c96c68856a7810f7c","edf8fbbfd3e69ebcda8c96c68856a7810f7c","edf8fbbfd3e69ebcda8c96c68c6bb188419d6e016b","f7fcfde0ecf4bfd3e69ebcda8c96c68c6bb188419d6e016b","f7fcfde0ecf4bfd3e69ebcda8c96c68c6bb188419d810f7c4d004b").map(r);const F=m(P);var D=new Array(3).concat("e0f3dba8ddb543a2ca","f0f9e8bae4bc7bccc42b8cbe","f0f9e8bae4bc7bccc443a2ca0868ac","f0f9e8ccebc5a8ddb57bccc443a2ca0868ac","f0f9e8ccebc5a8ddb57bccc44eb3d32b8cbe08589e","f7fcf0e0f3dbccebc5a8ddb57bccc44eb3d32b8cbe08589e","f7fcf0e0f3dbccebc5a8ddb57bccc44eb3d32b8cbe0868ac084081").map(r);const L=m(D);var B=new Array(3).concat("fee8c8fdbb84e34a33","fef0d9fdcc8afc8d59d7301f","fef0d9fdcc8afc8d59e34a33b30000","fef0d9fdd49efdbb84fc8d59e34a33b30000","fef0d9fdd49efdbb84fc8d59ef6548d7301f990000","fff7ecfee8c8fdd49efdbb84fc8d59ef6548d7301f990000","fff7ecfee8c8fdd49efdbb84fc8d59ef6548d7301fb300007f0000").map(r);const z=m(B);var Z=new 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t=0,e=this._hullStart;t<q;t++)this.hull[t]=e,e=n[e];this.triangles=this._triangles.subarray(0,this.trianglesLen),this.halfedges=this._halfedges.subarray(0,this.trianglesLen)}_hashKey(t,e){return Math.floor(function(t,e){const n=t/(Math.abs(t)+Math.abs(e));return(e>0?3-n:1+n)/4}(t-this._cx,e-this._cy)*this._hashSize)%this._hashSize}_legalize(t){const{_triangles:e,_halfedges:n,coords:r}=this;let 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=Yr[--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(Xr(r[2*f],r[2*f+1],r[2*d],r[2*d+1],r[2*h],r[2*h+1],r[2*p],r[2*p+1])){e[t]=p,e[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<Yr.length&&(Yr[o++]=a)}else{if(0===o)break;t=Yr[--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 Qr(t,e,n,r){const o=t-n,i=e-r;return o*o+i*i}function Xr(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=u*u+f*f,m=d*d+h*h;return l*(f*m-p*h)-c*(u*m-p*d)+(l*l+c*c)*(u*h-f*d)<0}function to(t,e,n,r,o,i){const s=n-t,a=r-e,l=o-t,c=i-e,u=s*s+a*a,f=l*l+c*c,d=.5/(s*c-a*l),h=(c*u-a*f)*d,p=(s*f-l*u)*d;return h*h+p*p}function eo(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;no(t,n+r>>1,o),e[t[n]]>e[t[r]]&&no(t,n,r),e[t[o]]>e[t[r]]&&no(t,o,r),e[t[n]]>e[t[o]]&&no(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;no(t,o,i)}t[n+1]=t[i],t[i]=s,r-o+1>=i-n?(eo(t,e,o,r),eo(t,e,n,i-1)):(eo(t,e,n,i-1),eo(t,e,o,r))}}function no(t,e,n){const r=t[e];t[e]=t[n],t[n]=r}function ro(t){return t[0]}function oo(t){return t[1]}const io=1e-6;class so{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)>io||Math.abs(this._y1-o)>io)&&(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 ao{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 lo{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(2*t.points.length),this.vectors=new Float64Array(2*t.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/3*2);for(let e,r,i=0,s=0,a=n.length;i<a;i+=3,s+=2){const a=2*n[i],l=2*n[i+1],c=2*n[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*(g*b-y*v);if(Math.abs(_)<1e-9){let o=1e9;const i=2*n[0];o*=Math.sign((t[i]-u)*b-(t[i+1]-f)*v),e=(u+p)/2-o*b,r=(f+m)/2+o*v}else{const t=1/_,n=g*g+y*y,o=v*v+b*b;e=u+(b*n-y*o)*t,r=f+(g*o-v*n)*t}o[s]=e,o[s+1]=r}let i,s,a,l=e[e.length-1],c=4*l,u=t[2*l],f=t[2*l+1];r.fill(0);for(let n=0;n<e.length;++n)l=e[n],i=c,s=u,a=f,c=4*l,u=t[2*l],f=t[2*l+1],r[i+2]=r[c]=a-f,r[i+3]=r[c+1]=u-s}render(t){const e=null==t?t=new so: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=2*Math.floor(e/3),s=2*Math.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=2*Math.floor(r[l]/3),c=i[n],u=i[n+1],f=4*a,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 so: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 so: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 ao;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[2*n],e[2*n+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=4*t;return n[r]||n[r+1]?this._clipInfinite(t,e,n[r],n[r+1],n[r+2],n[r+3]):this._clipFinite(t,e)}_clipFinite(t,e){const n=e.length;let r,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 co=2*Math.PI,uo=Math.pow;function fo(t){return t[0]}function ho(t){return t[1]}function po(t,e,n){return[t+Math.sin(t+e)*n,e+Math.cos(t-e)*n]}class mo{static from(t,e=fo,n=ho,r){return new mo("length"in t?function(t,e,n,r){const o=t.length,i=new Float64Array(2*o);for(let s=0;s<o;++s){const o=t[s];i[2*s]=e.call(r,o,s,t),i[2*s+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=2*e[t],o=2*e[t+1],i=2*e[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[2*t]-e[2*n]||e[2*t+1]-e[2*n+1]));const t=this.collinear[0],n=this.collinear[this.collinear.length-1],r=[e[2*t],e[2*t+1],e[2*n],e[2*n+1]],o=1e-8*Math.hypot(r[3]-r[1],r[2]-r[0]);for(let t=0,n=e.length/2;t<n;++t){const n=po(e[2*t],e[2*t+1],o);e[2*t]=n[0],e[2*t+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 lo(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=uo(e-l[2*t],2)+uo(n-l[2*t+1],2);const f=r[t];let d=f;do{let r=a[d];const f=uo(e-l[2*r],2)+uo(n-l[2*r+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&&uo(e-l[2*d],2)+uo(n-l[2*d+1],2)<u)return d;break}}while(d!==f);return c}render(t){const e=null==t?t=new so: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=2*o[e],a=2*o[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 so:void 0,{points:r}=this;for(let 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r=t.invertX(e[0][0])-n[0][0],o=t.invertX(e[1][0])-n[1][0],i=t.invertY(e[0][1])-n[0][1],s=t.invertY(e[1][1])-n[1][1];return t.translate(o>r?(r+o)/2:Math.min(0,r)||Math.max(0,o),s>i?(i+s)/2:Math.min(0,i)||Math.max(0,s))}function Up(){var t,e,n,r=Dp,o=Lp,i=$p,s=zp,a=Zp,l=[0,1/0],c=[[-1/0,-1/0],[1/0,1/0]],u=250,f=Cp.Z,d=x("start","zoom","end"),h=500,p=0,m=10;function g(t){t.property("__zoom",Bp).on("wheel.zoom",q,{passive:!1}).on("mousedown.zoom",N).on("dblclick.zoom",S).filter(a).on("touchstart.zoom",A).on("touchmove.zoom",M).on("touchend.zoom touchcancel.zoom",T).style("-webkit-tap-highlight-color","rgba(0,0,0,0)")}function y(t,e){return(e=Math.max(l[0],Math.min(l[1],e)))===t.k?t:new Ep(e,t.x,t.y)}function v(t,e,n){var r=e[0]-n[0]*t.k,o=e[1]-n[1]*t.k;return r===t.x&&o===t.y?t:new Ep(t.k,r,o)}function b(t){return[(+t[0][0]+ +t[1][0])/2,(+t[0][1]+ +t[1][1])/2]}function _(t,e,n,r){t.on("start.zoom",(function(){w(this,arguments).event(r).start()})).on("interrupt.zoom end.zoom",(function(){w(this,arguments).event(r).end()})).tween("zoom",(function(){var t=this,i=arguments,s=w(t,i).event(r),a=o.apply(t,i),l=null==n?b(a):"function"==typeof n?n.apply(t,i):n,c=Math.max(a[1][0]-a[0][0],a[1][1]-a[0][1]),u=t.__zoom,d="function"==typeof e?e.apply(t,i):e,h=f(u.invert(l).concat(c/u.k),d.invert(l).concat(c/d.k));return function(t){if(1===t)t=d;else{var e=h(t),n=c/e[2];t=new Ep(n,l[0]-e[0]*n,l[1]-e[1]*n)}s.zoom(null,t)}}))}function w(t,e,n){return!n&&t.__zooming||new k(t,e)}function k(t,e){this.that=t,this.args=e,this.active=0,this.sourceEvent=null,this.extent=o.apply(t,e),this.taps=0}function q(t,...e){if(r.apply(this,arguments)){var n=w(this,e).event(t),o=this.__zoom,a=Math.max(l[0],Math.min(l[1],o.k*Math.pow(2,s.apply(this,arguments)))),u=Vt(t);if(n.wheel)n.mouse[0][0]===u[0]&&n.mouse[0][1]===u[1]||(n.mouse[1]=o.invert(n.mouse[0]=u)),clearTimeout(n.wheel);else{if(o.k===a)return;n.mouse=[u,o.invert(u)],be(this),n.start()}Fp(t),n.wheel=setTimeout(f,150),n.zoom("mouse",i(v(y(o,a),n.mouse[0],n.mouse[1]),n.extent,c))}function f(){n.wheel=null,n.end()}}function N(t,...e){if(!n&&r.apply(this,arguments)){var o=t.currentTarget,s=w(this,e,!0).event(t),a=Dt(t.view).on("mousemove.zoom",d,!0).on("mouseup.zoom",h,!0),l=Vt(t,o),u=t.clientX,f=t.clientY;$t(t.view),Pp(t),s.mouse=[l,this.__zoom.invert(l)],be(this),s.start()}function d(t){if(Fp(t),!s.moved){var e=t.clientX-u,n=t.clientY-f;s.moved=e*e+n*n>p}s.event(t).zoom("mouse",i(v(s.that.__zoom,s.mouse[0]=Vt(t,o),s.mouse[1]),s.extent,c))}function h(t){a.on("mousemove.zoom mouseup.zoom",null),Ut(t.view,s.moved),Fp(t),s.event(t).end()}}function S(t,...e){if(r.apply(this,arguments)){var n=this.__zoom,s=Vt(t.changedTouches?t.changedTouches[0]:t,this),a=n.invert(s),l=n.k*(t.shiftKey?.5:2),f=i(v(y(n,l),s,a),o.apply(this,e),c);Fp(t),u>0?Dt(this).transition().duration(u).call(_,f,s,t):Dt(this).call(g.transform,f,s,t)}}function A(n,...o){if(r.apply(this,arguments)){var i,s,a,l,c=n.touches,u=c.length,f=w(this,o,n.changedTouches.length===u).event(n);for(Pp(n),s=0;s<u;++s)l=[l=Vt(a=c[s],this),this.__zoom.invert(l),a.identifier],f.touch0?f.touch1||f.touch0[2]===l[2]||(f.touch1=l,f.taps=0):(f.touch0=l,i=!0,f.taps=1+!!t);t&&(t=clearTimeout(t)),i&&(f.taps<2&&(e=l[0],t=setTimeout((function(){t=null}),h)),be(this),f.start())}}function M(t,...e){if(this.__zooming){var n,r,o,s,a=w(this,e).event(t),l=t.changedTouches,u=l.length;for(Fp(t),n=0;n<u;++n)o=Vt(r=l[n],this),a.touch0&&a.touch0[2]===r.identifier?a.touch0[0]=o:a.touch1&&a.touch1[2]===r.identifier&&(a.touch1[0]=o);if(r=a.that.__zoom,a.touch1){var f=a.touch0[0],d=a.touch0[1],h=a.touch1[0],p=a.touch1[1],m=(m=h[0]-f[0])*m+(m=h[1]-f[1])*m,g=(g=p[0]-d[0])*g+(g=p[1]-d[1])*g;r=y(r,Math.sqrt(m/g)),o=[(f[0]+h[0])/2,(f[1]+h[1])/2],s=[(d[0]+p[0])/2,(d[1]+p[1])/2]}else{if(!a.touch0)return;o=a.touch0[0],s=a.touch0[1]}a.zoom("touch",i(v(r,o,s),a.extent,c))}}function T(t,...r){if(this.__zooming){var o,i,s=w(this,r).event(t),a=t.changedTouches,l=a.length;for(Pp(t),n&&clearTimeout(n),n=setTimeout((function(){n=null}),h),o=0;o<l;++o)i=a[o],s.touch0&&s.touch0[2]===i.identifier?delete s.touch0:s.touch1&&s.touch1[2]===i.identifier&&delete s.touch1;if(s.touch1&&!s.touch0&&(s.touch0=s.touch1,delete s.touch1),s.touch0)s.touch0[1]=this.__zoom.invert(s.touch0[0]);else if(s.end(),2===s.taps&&(i=Vt(i,this),Math.hypot(e[0]-i[0],e[1]-i[1])<m)){var c=Dt(this).on("dblclick.zoom");c&&c.apply(this,arguments)}}}return g.transform=function(t,e,n,r){var o=t.selection?t.selection():t;o.property("__zoom",Bp),t!==o?_(t,e,n,r):o.interrupt().each((function(){w(this,arguments).event(r).start().zoom(null,"function"==typeof e?e.apply(this,arguments):e).end()}))},g.scaleBy=function(t,e,n,r){g.scaleTo(t,(function(){var t=this.__zoom.k,n="function"==typeof e?e.apply(this,arguments):e;return t*n}),n,r)},g.scaleTo=function(t,e,n,r){g.transform(t,(function(){var t=o.apply(this,arguments),r=this.__zoom,s=null==n?b(t):"function"==typeof n?n.apply(this,arguments):n,a=r.invert(s),l="function"==typeof e?e.apply(this,arguments):e;return i(v(y(r,l),s,a),t,c)}),n,r)},g.translateBy=function(t,e,n,r){g.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)},g.translateTo=function(t,e,n,r,s){g.transform(t,(function(){var t=o.apply(this,arguments),s=this.__zoom,a=null==r?b(t):"function"==typeof r?r.apply(this,arguments):r;return i(Rp.translate(a[0],a[1]).scale(s.k).translate("function"==typeof e?-e.apply(this,arguments):-e,"function"==typeof n?-n.apply(this,arguments):-n),t,c)}),r,s)},k.prototype={event:function(t){return t&&(this.sourceEvent=t),this},start:function(){return 1==++this.active&&(this.that.__zooming=this,this.emit("start")),this},zoom:function(t,e){return this.mouse&&"mouse"!==t&&(this.mouse[1]=e.invert(this.mouse[0])),this.touch0&&"touch"!==t&&(this.touch0[1]=e.invert(this.touch0[0])),this.touch1&&"touch"!==t&&(this.touch1[1]=e.invert(this.touch1[0])),this.that.__zoom=e,this.emit("zoom"),this},end:function(){return 0==--this.active&&(delete this.that.__zooming,this.emit("end")),this},emit:function(t){var e=Dt(this.that).datum();d.call(t,this.that,new Op(t,{sourceEvent:this.sourceEvent,target:g,type:t,transform:this.that.__zoom,dispatch:d}),e)}},g.wheelDelta=function(t){return arguments.length?(s="function"==typeof t?t:jp(+t),g):s},g.filter=function(t){return arguments.length?(r="function"==typeof t?t:jp(!!t),g):r},g.touchable=function(t){return arguments.length?(a="function"==typeof t?t:jp(!!t),g):a},g.extent=function(t){return arguments.length?(o="function"==typeof t?t:jp([[+t[0][0],+t[0][1]],[+t[1][0],+t[1][1]]]),g):o},g.scaleExtent=function(t){return arguments.length?(l[0]=+t[0],l[1]=+t[1],g):[l[0],l[1]]},g.translateExtent=function(t){return arguments.length?(c[0][0]=+t[0][0],c[1][0]=+t[1][0],c[0][1]=+t[0][1],c[1][1]=+t[1][1],g):[[c[0][0],c[0][1]],[c[1][0],c[1][1]]]},g.constrain=function(t){return arguments.length?(i=t,g):i},g.duration=function(t){return arguments.length?(u=+t,g):u},g.interpolate=function(t){return arguments.length?(f=t,g):f},g.on=function(){var t=d.on.apply(d,arguments);return t===d?g:t},g.clickDistance=function(t){return arguments.length?(p=(t=+t)*t,g):Math.sqrt(p)},g.tapDistance=function(t){return arguments.length?(m=+t,g):m},g}Ip.prototype=Ep.prototype},8828:(t,e,n)=>{"use strict";n.d(e,{H:()=>o,L:()=>r});class r 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