99764ad55bb121d285e9734de955bba41802ad06 max Wed Jul 15 23:35:19 2026 -0700 varFreqs: add gnomAD-Canada HostSeq SNV frequencies and fold into combined tracks, refs #36642 #Preview2 week - bugs introduced now will need a build patch to fix New "hostseq" vcfTabix subtrack of the SNV Frequencies container: gnomAD-Canada v1.0 / HostSeq, 10,487 Canadian COVID-19 WGS genomes on hg38. The release ships only as a ~104 GB Hail table, so hostseqHtToVcf.py reads it with Hail and flattens the freq array into a sites-only VCF with overall + 9 gnomAD ancestry-group AC/AN/AF, nhomalt, grpmax, dbSNP rsID and the variant filter status. 232,028,491 release rows -> 213,382,086 written (18,646,405 AC0 sites dropped). Registered HostSeq (is_disease=0) in databases.tsv and its 9 ancestry groups in populations.tsv, and rebuilt varFreqsAffected/varFreqsBackground so HostSeq feeds the background side (29 cohorts, 185 fields; merged set 1,374,129,993 variants). Added HostSeq to filterValues.backgroundSources. diff --git src/hg/makeDb/trackDb/human/hostseq.html src/hg/makeDb/trackDb/human/hostseq.html new file mode 100644 index 00000000000..affe24f63d9 --- /dev/null +++ src/hg/makeDb/trackDb/human/hostseq.html @@ -0,0 +1,114 @@ +<h2>Description</h2> +<p> +This track shows allele counts and frequencies from +<a href="https://www.bcgsc.ca/gnomad/" target="_blank">gnomAD-Canada</a>, the Canadian arm of the +Genome Aggregation Database. The v1.0 release aggregates whole-genome sequencing data from 10,487 +participants in the Canadian COVID-19 +<a href="https://www.cgen.ca/programs/hostseq" target="_blank">HostSeq</a> databank, a national initiative +launched in April 2020 that recruited people infected with SARS-CoV-2 together with controls from +fourteen clinical and epidemiological studies across Canada. Because the cohort was assembled to +study host susceptibility to a common infection rather than a rare genetic disease, it serves here +as a population-scale reference of Canadian genetic variation. +</p> +<p> +Frequencies are reported for the whole cohort and for nine genetic-ancestry groups inferred by the +gnomAD pipeline: African/African-American, Latino/Admixed-American, European (non-Finnish), +Ashkenazi Jewish, East Asian, European (Finnish), Middle Eastern, South Asian, and Remaining +individuals. The release contains about 213 million variant sites. The per-variant details page +also shows the group with the highest frequency (grpmax) and the gnomAD variant-quality filter +status. +</p> + +<h2>Display Conventions</h2> +<p> +This is a Variant Call Format (VCF) track. Hovering over a variant shows the overall allele +frequency, and clicking a variant opens a details page with the overall and per-ancestry allele +counts, allele numbers and frequencies, the dbSNP identifier, and the variant filter status. The +filter status is one of <tt>PASS</tt>, <tt>RF</tt> (failed the gnomAD random-forest +variant-quality filter), or <tt>InbreedingCoeff</tt> (excess heterozygosity); variants with zero +release allele count (<tt>AC0</tt>) are not shown. +</p> + +<h2>Data Access</h2> +<p> +The data can be explored interactively with the +<a href="../cgi-bin/hgTables">Table Browser</a> or the +<a href="../cgi-bin/hgIntegrator">Data Integrator</a>. +For programmatic access, our <a href="https://api.genome.ucsc.edu" target="_blank">REST API</a> +can be used; the track name is <em>hostseq</em>. +For bulk download, the VCF is available from +<a href="http://hgdownload.soe.ucsc.edu/gbdb/hg38/varFreqs/hostseq/" target="_blank">our download +server</a>. The original Hail table can be downloaded from the +<a href="https://www.bcgsc.ca/gnomad/" target="_blank">gnomAD-Canada portal</a>. +</p> + +<h2>Methods</h2> +<p> +Whole-genome sequencing was performed on 10,487 HostSeq participants at three CGEn sites on the +Illumina NovaSeq 6000 platform at 30X coverage. Reads were aligned to GRCh38 with the DRAGEN +mapper (DRAGMAP v1.3.0), de-duplicated with Picard (v2.25.0) and base-quality-recalibrated with +GATK (v4.2.5.0). Per-sample SNVs and indels were called with GATK HaplotypeCaller in DRAGEN mode, +and per-sample gVCFs were joint-genotyped with GATK GenotypeGVCFs. The joint callset was then run +through the Broad Institute's gnomAD QC v3 pipeline (adapted for on-premises use at the BC Cancer +Genome Sciences Centre), which performs sample quality control, relatedness and genetic-ancestry +inference by principal-component analysis, random-forest variant filtering, and computes overall +and per-ancestry allele frequencies. Full pipeline details are in the +<a href="https://www.bcgsc.ca/gnomad/download/README.pdf" target="_blank">release README</a> and +the HostSeq cohort reference below. +</p> +<p> +The release-sites Hail table (<tt>release_sites_hostseq.tar.gz</tt>, ~101 GB) was downloaded from +<a href="https://www.bcgsc.ca/gnomad/download/release_sites_hostseq.tar.gz" target="_blank">https://www.bcgsc.ca/gnomad/download/release_sites_hostseq.tar.gz</a> +and read with <a href="https://hail.is" target="_blank">Hail</a>. The overall and per-ancestry +allele counts, allele numbers and frequencies were flattened from the table's <tt>freq</tt> array +into VCF INFO fields, together with the dbSNP rsID and the variant filter status, and exported as a +sites-only VCF. The source table is already biallelic-split and uses UCSC chr-prefixed contigs, so +no allele-splitting or chromosome renaming was needed. Of the 232,028,491 variant rows in the +release table, 213,382,086 with a non-zero release allele count were written; the 18,646,405 +<tt>AC0</tt> sites (no observed allele in the high-quality release) were dropped. The source +covers the autosomes plus chrX and chrY. About 15% of the written variants (32,074,697) carry the +gnomAD <tt>RF</tt> quality-filter flag and 158,230 the <tt>InbreedingCoeff</tt> flag; the +remaining 181,149,159 are <tt>PASS</tt>. Filter-flagged variants are retained so the full release +is browsable, and can be hidden with the track's filter controls. +Processing documentation is in the +<a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/varFreqs.txt" +target="_blank">varFreqs makeDoc file</a>; the conversion script is in +<a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/scripts/varFreqs" +target="_blank">our GitHub scripts directory</a>. +</p> + +<h2>Credits</h2> +<p> +Data were generated by the gnomAD-Canada team as part of the Canadian Genomic Data Commons (CGDC) +and the Pan-Canadian Genome Library (PCGL), using CGEn's HostSeq databank (funded by the Government +of Canada through Genome Canada, Project DACO-18). Thanks to the HostSeq participants and to the +gnomAD-Canada project leadership (Jordan Lerner-Ellis, Steven Jones and Daniel Taliun) for making +the aggregate data publicly available. Per the data providers, no attempts should be made to +relabel the gnomAD-Canada genetic-ancestry groups. +</p> + +<h2>References</h2> + + +<p> +Yoo S, Garg E, Elliott LT, Hung RJ, Halevy AR, Brooks JD, Bull SB, Gagnon F, Greenwood C, Lawless JF +<em>et al</em>. +<a href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/37131148/" target="_blank"> +HostSeq: a Canadian whole genome sequencing and clinical data resource</a>. +<em>BMC Genom Data</em>. 2023 May 2;24(1):26. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/37131148" target="_blank">37131148</a>; PMC: <a +href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10152008/" target="_blank">PMC10152008</a> +</p> + + + +<p> +Chen S, Francioli LC, Goodrich JK, Collins RL, Kanai M, Wang Q, Alföldi J, Watts NA, Vittal C, +Gauthier LD <em>et al</em>. +<a href="https://doi.org/10.1038/s41586-023-06045-0" target="_blank"> +A genomic mutational constraint map using variation in 76,156 human genomes</a>. +<em>Nature</em>. 2024 Jan;625(7993):92-100. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/38057664" target="_blank">38057664</a>; PMC: <a +href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629659/" target="_blank">PMC11629659</a> +</p> +