15bdf707a4bde0a281109bb810499a2fa98ef6ac lrnassar Tue Jul 14 07:48:05 2026 -0700 Fix stale "row Y" reference in popEVE trailingFix comment per CR feedback. refs #37791 The amino acid row reorder made P the last row, not Y, but the trailingFix explanation in the converter comment and the makedoc still said "row Y, last column". Reworded both to be order-agnostic ("last row, last column"). Documentation only; the code already operates positionally on labelParts[-1]. diff --git src/hg/makeDb/doc/hg38/popEve.txt src/hg/makeDb/doc/hg38/popEve.txt index e1cd8256d86..a4d743dfb7b 100644 --- src/hg/makeDb/doc/hg38/popEve.txt +++ src/hg/makeDb/doc/hg38/popEve.txt @@ -1,80 +1,80 @@ # [Claude/lrnassar] popEVE - proteome-wide missense deleteriousness scores (2026-06-30) # popEVE places missense variants on a single proteome-wide, human-specific spectrum of # deleteriousness by calibrating EVE + ESM-1v evolutionary scores against UK Biobank # population variation with a Gaussian process. # Reference: Orenbuch et al. (2025) Nat Genet 57:3165-3174, PMID 41286104. # https://doi.org/10.1038/s41588-025-02400-1 # Data: the complete UKBB-trained GRCh38 VCF (popEVE v1.1, dated 2025-07-15) from the # pop.evemodel.org bulk downloads. The VCF carries, per missense substitution, genomic # coordinates plus INFO fields protein (RefSeq NP_), gene, mutant (e.g. E773D), # gap_frequency, popEVE, pop-adjusted_EVE, pop-adjusted_ESM1v, EVE, ESM1v. # Source size 1476124568 bytes, Last-Modified 2025-10-29. mkdir -p /hive/data/outside/popEve mkdir -p /hive/data/genomes/hg38/bed/popEve/sorttmp cd /hive/data/genomes/hg38/bed/popEve ln -s /hive/data/outside/popEve input cd /hive/data/outside/popEve wget -nv https://data.evemodel.org/popeve/v1.1/downloads/grch38_popEVE_ukbb_20250715.vcf.gz # The combined VCF is one position-sorted file with all proteins interleaved (overlapping # genes share positions), so records are grouped by protein on disk before conversion. # Each protein becomes one heatmap BED12+ entry: columns = amino acid positions at codon # genomic coordinates, rows = 20 standard amino acids ordered by class (A V L I M F Y W R H # K D E S T N Q G C P), matching the MaveDB heatmap track. Multiple codon changes encoding # the same amino acid substitution carry identical popEVE scores and are deduplicated. # Wildtype cells are empty. popEVE lists only positions carrying a missense alt, so a codon # may have only 2 of its 3 genomic positions; block sizes are clamped (min(3, gap-to-next)) # so adjacent codon blocks cannot overlap, which keeps the file valid for bedToBigBed. # Strand is taken from NCBI RefSeq (the VCF has no strand field), cross-checked against the # strand inferred from genomic-vs-protein-position direction. # Color: global cross-gene gradient keyed to raw popEVE; interior anchors at the published # severe (-5.056) and moderate (-4.617) cutoffs and the proteome median (~-3.5); outer # saturation anchors at the 0.5th / 99.5th percentiles of the proteome-wide distribution. # Records with popEVE=nan (e.g. start-codon M1 variants) are skipped. cd /hive/data/genomes/hg38/bed/popEve # Full build (download already done): strand map, extract, color anchors, sort, convert, # filter to chrom.sizes, bigBed. See runBuild.sh in this directory. bash runBuild.sh # runBuild.sh steps, in order: # 1. NP_->strand map: # hgsql hg38 -N -e "select distinct l.protAcc, g.chrom, g.strand from ncbiRefSeqLink l # join ncbiRefSeq g on g.name=l.mrnaAcc where l.protAcc like 'NP\_%'" # -> np_strand.tsv (prefer the strand on a primary chromosome) # 2. extract: zcat ...vcf.gz | extractPopEve.py > popEve_records.tsv # 3. color anchors: p0.5 / p99.5 of popEVE over all records -> anchors.txt # 4. sort -t$'\t' -k1,1 -k4,4n -S 4G -T sorttmp popEve_records.tsv > popEve_sorted.tsv # 5. vcfToPopEveHeatmap.py popEve_sorted.tsv np_strand.tsv popEve_raw.bed $LO $HI # 6. bedSort + awk filter to chrom.sizes -> popEve_filtered.bed # 7. bedToBigBed -type=bed12+ -tab -as=popEve_heatmap.as popEve_filtered.bed chrom.sizes popEve.bb # Scripts: ~/kent/src/hg/makeDb/scripts/popEve/{extractPopEve.py,vcfToPopEveHeatmap.py,popEve_heatmap.as} # Notes: # - popEVE is distributed as genomic SNVs, so only single-nucleotide-reachable missense # substitutions are scored; each heatmap column (codon) therefore has ~6-9 of 19 rows # filled. This is expected and sparser than the EVE track (which scores all 19). # - The heatmap renderer parses the score array (chopCommas, keeps trailing empty) and the # label array (chopByCharRespectDoubleQuotesKeepEmpty, drops one trailing empty) -# differently. When the last cell (row Y, last column) is empty the counts disagree and +# differently. When the last cell (last row, last column) is empty the counts disagree and # the track aborts; the converter sets a non-empty placeholder label on that one trailing # cell (its score stays empty so the cell is uncolored). trailingFix count below. # Build results: # records extracted: 66,400,085 (nan skipped: 15,156) # color anchors: loAnchor=-5.742 hiAnchor=-2.287 (popEVE p0.5 / p99.5; median -3.358) # proteins: 18,968 (18,343 distinct gene symbols; remainder are RefSeq isoforms) # amino-acid positions: 10,114,809; bases covered: 886,638,890 # strand: 0 inferred-vs-RefSeq mismatches; 25 proteins not in the RefSeq map (strand from # coordinate inference); 0 with no strand signal; 0 dropped by chrom.sizes filter # trailingFix (trailing empty cell relabeled): 15,555 proteins # mouseover: HTML multi-line labels (
/); component scores rounded to 3 dp; # missing/nan components shown as NA # popEve.bb size: 1,592,586,266 bytes mkdir -p /gbdb/hg38/popEve ln -sf /hive/data/genomes/hg38/bed/popEve/popEve.bb /gbdb/hg38/popEve/popEve.bb