3972ba54c468ace338d4a5578de1d20bf6c1f9ec lrnassar Mon Apr 20 15:39:26 2026 -0700 Adding Rule 4 (long-exon rule, Lindeboom 2016) to NMD Escape tracks and releasing on Apr. 22, 2026. refs #33737 Script: added a fourth rule to genePredNmdEsc. Coding exons longer than 400 bp (excluding the last coding exon, which is already covered by the 50 bp rule) are flagged as NMD-escape regions. Rebuilt the Gencode and NCBI RefSeq bigBed files. trackDb: - nmd.ra: appended "/400nt" to the nmdEsc longLabels, set nmdEscGencode default visibility to dense so the track is visible in cart-reset views, changed all four NMDetective subtracks from "visibility full" to "visibility hide", updated pennantIcon to the Apr. 22, 2026 release date and anchor. - nmd.html: mention long internal exons in the overview description, update the rule count from three to four. - nmdEscTranscripts.html: add the long-exon rule to the rule list and color legend (gold, #FFD700), expand the Background section with mechanisms for the intronless, start-proximal, and long-exon rules, correct the 50 bp rule description to include the entire last coding exon, fix Lindeboom 2016 author initials (RG -> RGH). News: - newsarch.html: add the 2026-04-22 NMD Escape news entry covering all four rules, with acknowledgements to Guido Neidhardt and Andreas Lahner for suggesting the track and the Decipher Genome Browser team for inspiring the visualization. - indexNews.html: add the front-page news link. makedoc: - nmd.txt: dated note for the Rule 4 rebuild. diff --git src/hg/makeDb/trackDb/human/hg38/nmd.html src/hg/makeDb/trackDb/human/hg38/nmd.html index 12e43733fcd..53369d39588 100644 --- src/hg/makeDb/trackDb/human/hg38/nmd.html +++ src/hg/makeDb/trackDb/human/hg38/nmd.html @@ -1,118 +1,119 @@ <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 site or in transcripts without any junction. +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. Two transcript sets are provided: </p> <ul> <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 transcripts.</li> </ul> <p> -Click either of the links to the track details here or above to show the three rules -that were used (50bp, intronless, 100bp). +Click either of the links to the track details here or above to show the four rules +that were used (50bp, intronless, 100bp, long exon >400nt). </p> <h3>NMDetective scores</h3> <p> Machine-learning predictions of NMD efficiency from <a href="https://www.ncbi.nlm.nih.gov/pubmed/27618451" target="_blank">Lindeboom et al. 2016</a>. Two models (A = random forest, B = decision tree) predict whether a PTC at each position will trigger NMD or allow escape. Positive scores indicate predicted NMD triggering; negative scores indicate predicted 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> </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">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>