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 @@ -1,129 +1,124 @@ <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>.