7bec995472122739bf0f076de2603708059c65ce lrnassar Wed May 13 17:23:37 2026 -0700 Adding NMDetective-AI subtracks (bigWig + bigBed) under the NMD Escape superTrack. refs #33737 Two new subtracks slotted between NMD Escape RefSeq and NMDetective-A (priorities 1.7 and 1.8): - nmdDetectiveAi - position-averaged predictions (bigWig) - nmdDetectiveAiBed - per-stop-gain predictions, one item per (transcript, codon, mutant codon), with diverging Okabe-Ito coloring and a pre-rendered mouseover Predictions are from Veiner et al. (bioRxiv 10.64898/2026.03.24.714003), covering MANE Select transcripts at Gencode v46. Verdict bins in the bigBed mouseover use the GMM-derived thresholds reported in the paper's Methods (-0.17 / +0.43), not symmetric +/- 0.3. Description page covers the +0.5 / -0.5 anchor convention, threshold derivation, and the pre-print status. diff --git src/hg/makeDb/doc/hg38/nmd.txt src/hg/makeDb/doc/hg38/nmd.txt index f7f5d65e39c..01a949610a4 100644 --- src/hg/makeDb/doc/hg38/nmd.txt +++ src/hg/makeDb/doc/hg38/nmd.txt @@ -141,15 +141,57 @@ ####################################################################### # Lindeboom et al. NMDetective scores (2025-03-23 max/Claude) # NMD efficiency predictions from Lindeboom et al. 2016, Nat Genet. # Four bedGraph custom track files downloaded to: # /hive/data/genomes/hg38/bed/nmd/lindeboom/ # Data downloaded from https://figshare.com/articles/dataset/NMDetective/7803398 # Custom track data in the session links from that page # - NMDetectiveA.ct - Random forest prediction of NMD efficiency # - NMDetectiveB.ct - Decision tree prediction of NMD efficiency # - nmdDectA-ptc.ct - Random forest, first out-of-frame PTC # - nmdDectB-ptc.ct - Decision tree, first out-of-frame PTC # Convert bedGraph custom tracks to bigWig and symlink from /gbdb: cd /hive/data/genomes/hg38/bed/nmd/lindeboom/ bash ~/kent/src/hg/makeDb/scripts/nmd/lindeboomToBigWig.sh + +####################################################################### +# NMDetective-AI per-stop-gain predictions (2026-05-13 max) +# Deep-learning NMD efficiency predictions for every possible stop-gain SNV +# in MANE Select transcripts (Gencode v46). From Veiner et al., NMDetective-AI +# manuscript (pre-print as of 2026-05). Source files from the Vejni/NMDetectiveAI +# GitHub repo: +# https://github.com/Vejni/NMDetectiveAI/blob/main/manuscript/supplementary/files/ +# Two files supplied by Marcell Veiner: +# NMDetectiveAI_MANE.bw.gz - bigWig, position-averaged predictions +# NMDetectiveAI_MANE.bed.gz - BED, one row per stop-gain mutation per transcript + +mkdir -p /hive/data/genomes/hg38/bed/nmd/nmdDetectAi && cd /hive/data/genomes/hg38/bed/nmd/nmdDetectAi + +# Download from the supplementary files dir of the GitHub repo +# (filenames as-is; gunzip in place) +gunzip -k NMDetectiveAI_MANE.bed.gz NMDetectiveAI_MANE.bw.gz + +# Recolor/rescore the BED via a small Python helper. The raw file has +# itemRgb=0,0,0 and score=int(prediction*1000); we replace these with a +# diverging Okabe-Ito ramp (blue = NMD-evading, vermillion = NMD-triggering, +# grey near zero) and a 0-1000 score linear in the [-1.2, 1.5] prediction +# range. The helper also appends a pre-rendered mouseover HTML column whose +# verdict bins use the binarization thresholds from the Veiner et al. Methods +# section (3-component GMM on gnomAD predictions): pred <= -0.17 = evading, +# -0.17 < pred < +0.43 = intermediate, pred >= +0.43 = triggering. +python3 ~/kent/src/hg/makeDb/scripts/nmd/nmdDetectAi/makeBigBed.py \ + NMDetectiveAI_MANE.bed nmdDetectAi.bed + +bedSort nmdDetectAi.bed nmdDetectAi.sorted.bed +bedToBigBed nmdDetectAi.sorted.bed ../../../chrom.sizes nmdDetectAi.bb \ + -tab -type=bed9+7 -as=${HOME}/kent/src/hg/makeDb/scripts/nmd/nmdDetectAi/nmdDetectAi.as + +# bigWig used as-is from the upstream file +ln -sf /hive/data/genomes/hg38/bed/nmd/nmdDetectAi/NMDetectiveAI_MANE.bw \ + /gbdb/hg38/nmd/nmdDetectAi.bw +ln -sf /hive/data/genomes/hg38/bed/nmd/nmdDetectAi/nmdDetectAi.bb \ + /gbdb/hg38/nmd/nmdDetectAi.bb + +# Counts (2026-05-13 build): +# bigBed: 4,099,055 stop-gain items at 3 bp (codon) resolution +# bigWig: prediction range -1.104 .. 1.487 (different scale from NMDetective-A/B)