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/nmdDetective.html src/hg/makeDb/trackDb/human/hg38/nmdDetective.html index 10bcc67b28a..d98aa28f542 100644 --- src/hg/makeDb/trackDb/human/hg38/nmdDetective.html +++ src/hg/makeDb/trackDb/human/hg38/nmdDetective.html @@ -1,70 +1,73 @@ <h2>Description</h2> <p> The <b>NMDetective</b> tracks display genome-wide predictions of nonsense-mediated mRNA -decay (NMD) efficiency from +decay (NMD) efficiency using the NMDetective-A and NMDetective-B models from +<a href="https://www.ncbi.nlm.nih.gov/pubmed/31659324" target="_blank">Lindeboom et al. 2019</a>, +trained on the NMD efficiency measure from <a href="https://www.ncbi.nlm.nih.gov/pubmed/27618451" target="_blank">Lindeboom et al. 2016</a>. NMDetective scores predict whether a premature termination codon (PTC) at a given position will trigger NMD and mRNA degradation, or whether the transcript will escape NMD and potentially produce a truncated protein. </p> <p> -Scores range from approximately −1 to +1. Positive values indicate that a PTC at -that position is predicted to trigger NMD (the mRNA is degraded). Negative values indicate +Scores range from 0 to 1. Values near 1 indicate that a PTC at +that position is predicted to trigger NMD (the mRNA is degraded). Values near 0 indicate that the PTC is predicted to escape NMD (the truncated mRNA may be translated into an -aberrant protein). Values near zero indicate intermediate or uncertain NMD efficiency. +aberrant protein). Values in between indicate intermediate NMD efficiency. </p> <h3>Subtracks</h3> <table class="descTbl"> <tr><th>Track</th><th>Description</th></tr> <tr><td><b>NMDetective-A</b></td> <td>Random forest model predicting NMD efficiency for all possible PTCs introduced by single-nucleotide variants. Explains ~71% of systematic variance in NMD efficiency.</td></tr> <tr><td><b>NMDetective-B</b></td> <td>Simplified decision tree model for all possible PTCs. Slightly lower accuracy (~68% variance explained) but more interpretable, making it suitable for clinical applications.</td></tr> <tr><td><b>NMDetective-A PTC</b></td> <td>Random forest model predicting NMD efficiency specifically for the first out-of-frame PTC introduced by frameshifting indel mutations.</td></tr> <tr><td><b>NMDetective-B PTC</b></td> <td>Decision tree model for the first out-of-frame PTC from frameshifting indels.</td></tr> </table> <h2>Display Conventions and Configuration</h2> <p> -Each subtrack is displayed as a signal (bigWig) track. By default, the vertical axis -ranges from −1 to +1. Regions with positive values (predicted NMD-triggering) are -shown above the baseline; regions with negative values (predicted NMD escape) are shown -below. +Each subtrack is displayed as a signal (bigWig) track. Values closer to 1 indicate +predicted NMD-triggering, while values closer to 0 indicate predicted NMD escape. </p> <ul> <li><font color="#0080FF"><b>Blue tracks</b></font> (NMDetective-A and -B): predictions for all possible PTCs from single-nucleotide nonsense variants.</li> <li><font color="#009966"><b>Green tracks</b></font> (NMDetective-A PTC and -B PTC): predictions for the first out-of-frame PTC from frameshifting indels.</li> </ul> <h2>Methods</h2> <p> -The NMDetective models were trained on somatic nonsense mutation data from 9,769 cancer -patients and validated with frameshift mutations and germline variants -(<a href="https://www.ncbi.nlm.nih.gov/pubmed/31659324" target="_blank">Lindeboom et al. 2019</a>). +<b>NMDetective-A</b> and <b>NMDetective-B</b> were introduced in +<a href="https://www.ncbi.nlm.nih.gov/pubmed/31659324" target="_blank">Lindeboom et al. 2019</a>, +trained on NMD efficiency scores derived from somatic nonsense mutation data from 9,769 cancer +patients +(<a href="https://www.ncbi.nlm.nih.gov/pubmed/27618451" target="_blank">Lindeboom et al. 2016</a>), +and tested on an independent set of frameshift mutations. The models incorporate the following features to predict NMD efficiency: </p> <ul> <li>Whether the PTC falls in the last exon</li> <li>Distance to the last 50 nt of the penultimate exon (the EJC-based “50 bp rule”)</li> <li>Distance from the coding start (start-proximal NMD insensitivity)</li> <li>Exon length</li> <li>mRNA half-life</li> <li>Distance to the downstream exon-junction complex</li> <li>Distance to the wild-type stop codon</li> </ul> <p> <b>NMDetective-A</b> (random forest regression) captures non-linear interactions among these features and achieves the highest predictive accuracy.