ef70dfff0e8710e8aa4bc369a939f838c75947fb lrnassar Fri Jun 5 14:59:06 2026 -0700 varFreqs: Phase-7 audit cleanup on the supertrack and combined-track description pages. Supertrack varFreqs.html: - Restore the consequence-filter "Other" bucket explanation that was lost when varFreqsAll.html was replaced by the Affected+Background pair (now documented once on the supertrack page, since all three combined tracks share the filter). - Add 6 primary citations that were already in standalone subtrack pages but not carried up: Bycroft (UK Biobank), Cao (ChinaMAP), Cong (WBBC), Genome of the Netherlands Consortium (GoNL), Malomane (Saudi), Yang (TPMI). - Reorder Ameur, Singh into correct alphabetical position. - Lowercase <A HREF= -> <a href= per house style. varFreqsArray.html: - Replace four stale hgTrackUi?g=varFreqsAll links with the appropriate sibling combined tracks (varFreqsAffected / varFreqsBackground) or the supertrack. - Match the consequence color table style to varFreqsAffected.html and varFreqsBackground.html (color swatch instead of named-color text). refs #36642 diff --git src/hg/makeDb/trackDb/human/varFreqsArray.html src/hg/makeDb/trackDb/human/varFreqsArray.html index 44a7f29e44e..da0c5f25410 100644 --- src/hg/makeDb/trackDb/human/varFreqsArray.html +++ src/hg/makeDb/trackDb/human/varFreqsArray.html @@ -1,181 +1,176 @@ <h2>Description</h2> <p> This track merges variants from three genotyping-array cohorts into a single bigBed file with predicted protein consequences and cross-database filtering. It contains 14.7 million variants from the Taiwan Precision Medicine Initiative (TPMI Axiom TPM1 chip, ~1 million Han Chinese), the Mexico Biobank (MexBB, 6,011 individuals), and UK Biobank (361k unrelated white British, imputed from the Neale Lab Round 2 release). </p> <p> -The array track is kept separate from the -<a href="hgTrackUi?g=varFreqsAll">All Databases Combined</a> WGS/WES summary so that +The array track is kept separate from the sequencing-based combined tracks +(<a href="hgTrackUi?g=varFreqsAffected">Affected/Case Individuals</a> and +<a href="hgTrackUi?g=varFreqsBackground">Population + Unaffected</a>) so that sequencing-based and array-based frequencies can be inspected independently. For a summary of all available variant frequency databases, see the <a href="hgTrackUi?g=varFreqs">SNV Frequencies</a> supertrack page. </p> <h2>Display Conventions</h2> <h3>Color by Consequence</h3> <p>Variants are colored by their most severe predicted consequence:</p> <table class="stdTbl"> <tr><th>Color</th><th>Consequence class</th><th>Examples</th></tr> -<tr> - <td style="background-color: rgb(255,0,0); color: white; text-align: center;"><b>Red</b></td> - <td>Protein-truncating / Loss-of-function</td> - <td>stop_gained, frameshift, splice_donor, splice_acceptor, stop_lost, start_lost</td> -</tr> -<tr> - <td style="background-color: rgb(31,119,180); color: white; text-align: center;"><b>Blue</b></td> - <td>Missense / In-frame</td> - <td>missense, inframe_insertion, inframe_deletion, protein_altering</td> -</tr> -<tr> - <td style="background-color: rgb(0,128,0); color: white; text-align: center;"><b>Green</b></td> +<tr><th style="background-color:#FF0000;width:2em"> </th> + <td>Protein-truncating / loss-of-function</td> + <td>stop_gained, frameshift, splice_donor, splice_acceptor, stop_lost, start_lost</td></tr> +<tr><th style="background-color:#1F77B4;width:2em"> </th> + <td>Missense / in-frame</td> + <td>missense, inframe_insertion, inframe_deletion, protein_altering</td></tr> +<tr><th style="background-color:#008000;width:2em"> </th> <td>Synonymous</td> - <td>synonymous, stop_retained</td> -</tr> -<tr> - <td style="background-color: rgb(128,128,128); color: white; text-align: center;"><b>Grey</b></td> - <td>Non-coding / Intergenic</td> - <td>intron, non_coding, intergenic, UTR</td> -</tr> + <td>synonymous, stop_retained</td></tr> +<tr><th style="background-color:#808080;width:2em"> </th> + <td>Non-coding / intergenic</td> + <td>intron, non_coding, intergenic, UTR</td></tr> </table> <h3>Amino Acid Change Notation</h3> <p> The "AA change" field uses bcftools csq notation: <b>23I>23V</b> means position 23 changed from Isoleucine (I) to Valine (V) (missense). <b>23I</b> alone (no arrow) means position 23 is Isoleucine and unchanged (synonymous). A "*" indicates a stop codon (e.g. 45R>45* is a stop_gained). </p> <h2>Caveats</h2> <p> Allele frequencies from genotyping arrays are not directly comparable to those from whole-genome or whole-exome sequencing. Two limitations to keep in mind: </p> <ul> <li><b>Probe coverage is sparse and curated.</b> Array variants are only those the manufacturer designed probes for. Absence from this track does <em>not</em> mean a variant is absent in that population, only that it was not on the chip.</li> <li><b>Per-variant call confidence varies and is sometimes unreported.</b> TPMI publishes a per-probe <code>NGS_concordance</code> value (chip-vs-sequencing concordance from its own validation) in the source VCF; high-AF claims with low concordance are common. MexBB ships only AN/AF/AC with no FILTER column and no per-site QC at all. For both arrays, high-AF rare-disease candidates should be cross-checked against the - sequencing-based <a href="hgTrackUi?g=varFreqsAll">All Databases Combined</a> track - before drawing conclusions.</li> + sequencing-based + <a href="hgTrackUi?g=varFreqsBackground">Population + Unaffected</a> track before + drawing conclusions.</li> </ul> <h2>Filters</h2> <p> This track supports filtering via the track settings page. Click the track title or use the "Configure" button to access filters. </p> <h3>Variant Type and Consequence</h3> <ul> <li><b>Variant Type</b>: SNV, Insertion, Deletion, or MNV.</li> <li><b>Consequence</b>: Missense, Synonymous, Stop Gained, Frameshift, Splice Donor, Splice Acceptor, Intron, 3' UTR, 5' UTR, Non-coding, Intergenic, or Other. The filter uses OR logic across the comma-separated consequence tokens on each variant. See the - <a href="hgTrackUi?g=varFreqsAll">All Databases Combined</a> description page for a - complete description of the "Other" bucket.</li> + <a href="hgTrackUi?g=varFreqs">SNV Frequencies</a> supertrack page for a complete + description of the "Other" bucket.</li> </ul> <h3>Frequency and Count Filters</h3> <ul> <li><b>Max Allele Frequency</b>: Filter by the maximum AF observed across the three array sources.</li> <li><b>Total Allele Count</b>: Filter by the sum of allele counts across all three databases.</li> <li><b>Per-database AF and AC</b>: Filter by allele frequency or count in any specific source (TPMI Taiwan, Mexico Biobank, UK Biobank imputed).</li> </ul> <h3>Source Database</h3> <p> The <b>Source Database</b> filter restricts the display to variants present in specific databases. It uses OR logic. </p> <h3>Length Filters</h3> <ul> <li><b>Reference/Alternate Length</b>: Filter by the length of the reference or alternate allele.</li> <li><b>Length Change</b>: Filter by the size difference between alternate and reference (positive = insertion, negative = deletion, zero = SNV or MNV).</li> </ul> <h2>Methods</h2> <p> -The same merge-and-annotate pipeline used for the -<a href="hgTrackUi?g=varFreqsAll">All Databases Combined</a> track was run on the +The same merge-and-annotate pipeline used for the sequencing-based combined tracks +(<a href="hgTrackUi?g=varFreqsAffected">Affected/Case Individuals</a> and +<a href="hgTrackUi?g=varFreqsBackground">Population + Unaffected</a>) was run on the array-cohort subset of source VCFs. Each VCF was stripped of its INFO fields, normalized with <code>bcftools norm</code> (splitting multi-allelic sites), and merged with <code>bcftools merge</code>. The merged VCF was then annotated with predicted protein consequences using <code>bcftools csq</code> with the <a href="https://www.ensembl.org/info/data/ftp/index.html" target="_blank">Ensembl</a> GRCh38 release 115 gene annotation (GFF3). </p> <p> The track's <a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/varFreqs.txt" target="_blank">makeDoc file</a> documents how each source VCF was converted. Scripts are available from <a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/scripts/varFreqs" target="_blank">Github</a>. </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>varFreqsArray</em>. </p> <p> Because the merged callset includes data from multiple sources whose redistribution licenses differ, the combined bigBed is <b>not available for download</b> from our download server. The combined track can be reconstructed from the individual source VCFs using the <a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/scripts/varFreqs" target="_blank">conversion scripts on GitHub</a> together with the <a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/varFreqs.txt" target="_blank">build documentation</a>. </p> <h2>Credits</h2> <p> This track is only possible thanks to the participants in TPMI, the Mexico Biobank, and UK Biobank, who donated samples and provided health information. Click on the individual TPMI, MexBB, or UK Biobank subtracks in the <a href="hgTrackUi?g=varFreqs">SNV Frequencies</a> supertrack for full project credits. Thanks to Alex Ioannidis, UCSC, for the motivation for this track family and to Andreas Lahner, MGZ, for feedback. </p> <h2>References</h2> <p> For primary citations of each source dataset, see the References section on the <a href="hgTrackUi?g=varFreqs">SNV Frequencies</a> supertrack page. The merged-track build itself uses the following tools: </p> <p> Danecek P, McCarthy SA. <a href="https://doi.org/10.1093/bioinformatics/btx100" target="_blank"> BCFtools/csq: haplotype-aware variant consequences</a>. <em>Bioinformatics</em>. 2017 Jul 1;33(13):2037-2039. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/28205675" target="_blank">28205675</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870570/" target="_blank">PMC5870570</a> </p> <p> McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P, Cunningham F. <a href="https://doi.org/10.1186/s13059-016-0974-4" target="_blank"> The Ensembl Variant Effect Predictor</a>. <em>Genome Biol</em>. 2016 Jun 6;17(1):122. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/27268795" target="_blank">27268795</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893825/" target="_blank">PMC4893825</a> </p>