bf62c01cee8dc176445aa131e2fd6ea847a4eb68 lrnassar Thu May 28 11:32:52 2026 -0700 Adding UMD TP53 variant track (umdTp53) on hg19 and hg38 under a new Locus-Specific superTrack. refs #37648 Shows variants from the UMD TP53 database (p53.fr, Soussi & Leroy) as a bigBed 9+, one row per unique TP53 variant. Coloured by curator pathogenicity classification. Filters: pathogenicity, variantClassification, variantType, tumor frequency. Search by HGVS cDNA name and canonical protein change via extraIndex + trix. Linkouts to COSMIC and dbSNP. Otto pipeline polls p53.fr weekly; rebuilds only when the upstream zips actually change. Cron-silent on no-op so unchanged weeks don't email. Adds src/hg/utils/otto/umdTp53/ (build scripts + parser + .as schema), src/hg/makeDb/trackDb/human/umdTp53.ra (track stanza), src/hg/makeDb/trackDb/human/umdTp53.html (description page), src/hg/makeDb/trackDb/human/locusSpec.ra (shared superTrack definition). Includes locusSpec.ra and umdTp53.ra from human/trackDb.ra (alpha-gated). Adds include of ../locusSpec.ra to human/hs1/trackDb.ra so the strict trackDb checker resolves the parent in the same include chain as the existing mucins children. Drops the redundant locusSpec stanza from human/mucins.ra now that it lives in its own file. diff --git src/hg/makeDb/trackDb/human/umdTp53.html src/hg/makeDb/trackDb/human/umdTp53.html new file mode 100644 index 00000000000..5e373d871c0 --- /dev/null +++ src/hg/makeDb/trackDb/human/umdTp53.html @@ -0,0 +1,140 @@ +<h2>Description</h2> + +<p> +This track shows variants of the human <em>TP53</em> tumor-suppressor gene from the +<a href="https://p53.fr" target="_blank">UMD TP53 database</a>, a locus-specific +variant database maintained by Thierry Soussi and Bernard Leroy. It is a +comprehensive, curated resource for <em>TP53</em> mutations in human cancer, +integrating data from tumours, cell lines, germline (Li-Fraumeni syndrome and other +hereditary conditions), and non-neoplastic diseases reported in the published +literature. +</p> + +<p> +The track is built from the database's variant file, which lists each unique +<em>TP53</em> variant once. For every variant the database provides curated +metadata including a pathogenicity classification, the residual transactivation +activity of the mutant protein on eight p53 target promoters, functional impact +predictions from multiple algorithms (SIFT, PolyPhen-2, MutationAssessor, PROVEAN, +Condel, MutPred Splice), and frequencies in tumours, cell lines, somatic samples, +and germline cases. +</p> + +<p> +<em>TP53</em> hot spots such as p.R175H, p.R248Q, p.R248W, p.R273H, p.R273C, and +p.R282W are visible as the densely-recurrent positions in the DNA-binding domain. +</p> + +<h2>Display Conventions and Configuration</h2> + +<p> +Each variant is shown as a single coloured box at its genomic position. The colour +encodes the database's pathogenicity classification: +</p> + +<table style="border-spacing: 12px 2px"> + <tr><td style="background:#d42a2a; width:24px"> </td><td>Pathogenic</td></tr> + <tr><td style="background:#e65a32; width:24px"> </td><td>Likely Pathogenic</td></tr> + <tr><td style="background:#f7941d; width:24px"> </td><td>Possibly pathogenic</td></tr> + <tr><td style="background:#e6cd00; width:24px"> </td><td>VUS (variant of uncertain significance)</td></tr> + <tr><td style="background:#288c50; width:24px"> </td><td>Benign</td></tr> + <tr><td style="background:#a0a0a0; width:24px"> </td><td>Unknown</td></tr> +</table> + +<p> +Hovering over a variant displays its HGVS cDNA name, protein change on the canonical +TP53 alpha isoform (NP_000537.3), pathogenicity call, effect class, tumour frequency, +total occurrence count, and the curator note on residual transactivation activity. +Clicking opens the full details page with the per-promoter activity values, all +algorithm-level predictions and scores, the structural domain annotation, links to +COSMIC and dbSNP, and the curator's final comment. +</p> + +<p> +The track configuration page supports filters on: +</p> + +<ul> + <li><b>Pathogenicity classification</b> — multi-select dropdown</li> + <li><b>Variant classification</b> — missense, nonsense, synonymous, frameshift, + splice, intronic, UTR, etc.</li> + <li><b>Variant type</b> — SNP, DEL, INS, DNP, TNP, ONP</li> + <li><b>Minimum tumour frequency (%)</b> — numeric range slider</li> +</ul> + +<p> +Variants can be searched from the position box by HGVS cDNA name +(e.g. <b>c.524G>A</b>) or by canonical protein change (e.g. <b>p.R175H</b>). +</p> + +<h2>Data Updates</h2> + +<p> +The track is rebuilt automatically when a new release of the UMD TP53 database is +detected at <a href="https://p53.fr/download-the-database" target="_blank">p53.fr</a>. +</p> + +<h2>Data Access</h2> + +<p> +The raw data can be explored interactively with the +<a href="hgTables">Table Browser</a> or the +<a href="hgIntegrator">Data Integrator</a>. The underlying +<a href="../goldenPath/help/bigBed.html">bigBed</a> file may be downloaded directly +from <code>/gbdb/$db/bbi/umdTp53/umdTp53.bb</code>, and the data can be +queried programmatically through the +<a href="https://api.genome.ucsc.edu" target="_blank">REST API</a> via the track name +<b>umdTp53</b>. +</p> + +<h2>Methods</h2> + +<p> +The variants file from p53.fr (<code>UMD_variants_US.tsv</code>, one row per unique +<em>TP53</em> variant) was reformatted to +<a href="../goldenPath/help/bigBed.html">bigBed</a>. For hg19, genomic coordinates +were taken directly from the variants file's <code>HG19_Start</code> and +<code>HG19_End</code> columns. The variants file does not ship hg38 coordinates, so +for hg38 the coordinates were joined from the companion mutations file +(<code>UMD_mutations_US.tsv</code>), which contains both hg19 and hg38 positions for +every variant. +</p> + +<p> +The curator's residual-activity comment column derives from the eight-promoter +transactivation assay of Kato <em>et al.</em>, 2003: for missense variants, the +median of the eight per-promoter activities (expressed as % of wild-type) is mapped +to one of <em>Fully active</em>, <em>Hyper active</em>, <em>Partial activity</em>, +<em>No activity</em>, or <em>No data</em>. For nonsense, frameshift, splice-site, and +similar variants where the assay does not directly apply, the column carries an +explanatory note (e.g. <em>The activity of truncated p53 is assumed to be nil</em>). +The eight raw per-promoter values are available on the details page. +</p> + +<h2>Credits</h2> + +<p> +Thanks to Thierry Soussi, Bernard Leroy, and the UMD TP53 database curators for +maintaining the resource and making it available for download. +</p> + +<h2>References</h2> + +<p> +Leroy B, Anderson M, Soussi T. +<a href="https://doi.org/10.1002/humu.22552" target="_blank"> +TP53 mutations in human cancer: database reassessment and prospects for the next +decade</a>. +<em>Hum Mutat</em>. 2014 Jun;35(6):672-88. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/24665023" target="_blank">24665023</a> +</p> + +<p> +Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. +<a href="https://www.pnas.org/doi/10.1073/pnas.1431692100" target="_blank"> +Understanding the function-structure and function-mutation relationships of p53 +tumor suppressor protein by high-resolution missense mutation analysis</a>. +<em>Proc Natl Acad Sci U S A</em>. 2003 Jul 8;100(14):8424-9. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/12826609" target="_blank">12826609</a>; +PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166245/" target="_blank">PMC166245</a> +</p>