b86eab362ce697c350764ffe438ccdba8829e0f3 gperez2 Mon Jul 20 17:37:35 2026 -0700 Fixing the NMDetective-A/B score-range text (0 to 1, not -1 to +1), updating the citation to Lindeboom et al. 2019, and changing viewLimits to -0.3:1.5 on all four NMDetective subtracks. refs #37843 diff --git src/hg/makeDb/trackDb/human/hg38/nmd.html src/hg/makeDb/trackDb/human/hg38/nmd.html index 58e22b0acce..0747c3cea4e 100644 --- src/hg/makeDb/trackDb/human/hg38/nmd.html +++ src/hg/makeDb/trackDb/human/hg38/nmd.html @@ -1,130 +1,135 @@ <h2>Description</h2> <p> NMD is a cellular quality control mechanism that detects and degrades mRNAs containing premature termination codons (PTCs), preventing the accumulation of truncated, potentially harmful proteins. However, not all PTCs trigger NMD. PTCs in certain regions of a transcript are predicted to escape NMD, meaning the truncated mRNA may be translated into a protein with unpredictable functional consequences. The <b>NMD Escape</b> container includes several tracks that display putative regions where PTC variants are assumed to escape the NMD mechanism. These are typically located close to the first or last splice junction, within unusually long coding exons, or in transcripts without any junction. </p> <h2>Subtracks</h2> <h3>NMD escape regions</h3> <p> Rule-based predictions of NMD escape regions, computed from transcript annotations. Three transcript sets are provided: </p> <ul> <li><b><a href="hgTrackUi?g=nmdEscMane">NMD escape MANE</a></b>: NMD escape regions derived from the MANE Select plus MANE Plus Clinical transcript set, a jointly curated NCBI/EBI annotation that defines a single high-confidence transcript per protein-coding gene (Select), supplemented by additional transcripts of clinical importance (Plus Clinical).</li> <li><b><a href="hgTrackUi?g=nmdEscGencode">NMD escape Gencode</a></b>: NMD escape regions derived from GENCODE V49 transcripts.</li> <li><b><a href="hgTrackUi?g=nmdEscNcbiRefSeq">NMD escape NCBI RefSeq</a></b>: NMD escape regions derived from NCBI RefSeq Curated transcripts (NM_ and NR_ accessions only).</li> </ul> <p> Click either of the links to the track details here or above to show the four rules that were used (50 bp, intronless, 100 bp, long exon >400 nt). </p> <h3>NMDetective scores</h3> <p> Machine-learning predictions of NMD efficiency from +<a href="https://www.ncbi.nlm.nih.gov/pubmed/31659324" target="_blank">Lindeboom +et al. 2019</a> (NMDetective-A and NMDetective-B models, trained on <a href="https://www.ncbi.nlm.nih.gov/pubmed/27618451" target="_blank">Lindeboom -et al. 2016</a> (A and B models) and from Veiner <em>et al.</em> -(NMDetective-AI, pre-print 2026). Positive scores indicate predicted NMD -triggering; negative scores indicate predicted escape. +et al. 2016</a>) and from Veiner <em>et al.</em> +(NMDetective-AI, pre-print 2026). NMDetective-A and NMDetective-B scores range +from 0 to 1, with values near 1 indicating predicted NMD triggering and values +near 0 indicating predicted escape. NMDetective-AI uses a different scale, +roughly -1.1 to +1.5, with higher values indicating triggering and lower +values indicating escape. </p> <ul> <li><b><a href="hgTrackUi?g=nmdDetectiveA">NMDetective-A</a></b>: Random forest model for all possible PTCs from nonsense variants.</li> <li><b><a href="hgTrackUi?g=nmdDetectiveB">NMDetective-B</a></b>: Decision tree model for all possible PTCs from nonsense variants.</li> <li><b><a href="hgTrackUi?g=nmdDetectiveA_ptc">NMDetective-A PTC</a></b>: Random forest model for the first out-of-frame PTC from frameshifting indels.</li> <li><b><a href="hgTrackUi?g=nmdDetectiveB_ptc">NMDetective-B PTC</a></b>: Decision tree model for the first out-of-frame PTC from frameshifting indels.</li> <li><b><a href="hgTrackUi?g=nmdDetectiveAi">NMDetective-AI</a></b> and <b><a href="hgTrackUi?g=nmdDetectiveAiBed">NMDetective-AI variants</a></b>: Deep-learning model on MANE Select transcripts (GENCODE V46). Signal track shows the position-averaged prediction; variants track shows one item per stop-gain mutation per codon.</li> </ul> <h2>Background</h2> <p> The ACMG guidelines say under PVS1: </p> <p> <i> (ii) One must also be cautious when interpreting truncating variants downstream of the most 3′ truncating variant established as pathogenic in the literature. This is especially true if the predicted stop codon occurs in the last exon or in the last 50 base pairs of the penultimate exon, such that nonsense-mediated decay would not be predicted, and there is a higher likelihood of an expressed protein. </i> </p> <h2>Data Access</h2> <p> The data underlying these tracks 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 automated analysis, the data may be queried from our <a href="/goldenPath/help/api.html">REST API</a>. Please refer to our <a href="https://groups.google.com/a/soe.ucsc.edu/forum/#!forum/genome" target="_blank">mailing list archives</a> for questions, or our <a href="../FAQ/FAQdownloads.html#download36">Data Access FAQ</a> for more information. </p> <h2>Credits</h2> <p> Thanks to Guido Neidhardt for suggesting this track at HUGO VEPTC 2025 and Andreas Lahner for feedback. Thanks to the Decipher Genome Browser team for introducing the idea of a track. Thanks to Rik Lindeboom for providing custom tracks. </p> <h2>References</h2> <p> Kurosaki T, Popp MW, Maquat LE. <a href="https://doi.org/10.1038/s41580-019-0126-2" target="_blank"> Quality and quantity control of gene expression by nonsense-mediated mRNA decay</a>. <em>Nat Rev Mol Cell Biol</em>. 2019 Jul;20(7):406-420. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/30992545" target="_blank">30992545</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855384/" target="_blank">PMC6855384</a> </p> <p> Lindeboom RGH, Supek F, Lehner B. <a href="https://doi.org/10.1038/ng.3664" target="_blank"> The rules and impact of nonsense-mediated mRNA decay in human cancers</a>. <em>Nat Genet</em>. 2016 Oct;48(10):1112-8. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/27618451" target="_blank">27618451</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045715/" target="_blank">PMC5045715</a> </p> <p> Lindeboom RGH, Vermeulen M, Lehner B, Supek F. <a href="https://doi.org/10.1038/s41588-019-0517-5" target="_blank"> The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy</a>. <em>Nat Genet</em>. 2019 Nov;51(11):1645-1651. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/31659324" target="_blank">31659324</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858879/" target="_blank">PMC6858879</a> </p> <p> Nagy E, Maquat LE. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0968-0004(98)01208-0" target="_blank"> A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance</a>. <em>Trends Biochem Sci</em>. 1998 Jun;23(6):198-9. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/9644970" target="_blank">9644970</a> </p>