691a2b8981d6db69e8707ea44041c4661cdac97e max Wed Sep 9 06:38:29 2026 -0700 Imprinting: add the ASM Atlas tracks, and tidy the collection's labels Adds a composite built from Rosenski et al. 2025, "Atlas of imprinted and allele-specific DNA methylation in the human body". Three subtracks: the 458 regions whose methylation follows the parent of origin, the 72 known control regions with the boundaries the paper redrew, and the pool of 385,235 regions carrying two methylation states that those came out of. A fourth set, the regions whose methylation follows a nearby SNP, is built by the scripts but its stanza is commented out, since sequence driven methylation is not imprinting. The authors released hg19 only, so all three are lifted. Their published files are close to bare BED, so the SNPs, cell types, p-values, gene links and gamete methylation on the details pages are read out of the paper's supplementary tables and joined on by position. Regions that lift but change length by more than 10%, because hg38 added sequence inside them, are kept with a note rather than dropped: one of them is TCEB3C, the only control region on chr18. Also across the collection: - long labels name their source right after "Imprinting", so that a label read on its own says where the data came from - the two gene catalogs are worded alike, and ordered OMIM, Geneimprint, MethBase2, Akbari, ASM Atlas - the OMIM curators confirmed that their (I) marker covers established and candidate imprinted genes alike, with nothing in the export to tell them apart. Labels, description page and makeDoc now say so, and the claim that the set is "more conservative" than the computational tracks is gone. The bigBed was rebuilt for the autoSql line, same 459 features. - every subtrack page opens by naming the collection, linked back to its hgTrackUi page, and no longer repeats the collection page's introduction to imprinting refs #37599 diff --git src/hg/makeDb/doc/hg38/imprinting.txt src/hg/makeDb/doc/hg38/imprinting.txt index 53b5f82c702..8395c72dd00 100644 --- src/hg/makeDb/doc/hg38/imprinting.txt +++ src/hg/makeDb/doc/hg38/imprinting.txt @@ -1,253 +1,258 @@ # Imprinting track collection on hg38, refs #37599 # 2026-09-03 Claude-max # The "Imprinting" superTrack collects annotations of imprinted loci and of the # allele-specific methylation that marks them. ############################################################################## # MethBase2 ASM - allele-specific methylation fraction across methylomes # (refs #37599, data source is the MethBase2 hub, refs #36320) ############################################################################## # The MethBase2 track hub (Andrew D. Smith, USC) publishes an assembly-wide # summary bigWig under its "common" section. For each CpG site it holds the # fraction of MethBase2 hg38 methylomes in which that site fell inside an # allelically methylated region called by "dnmtools amrfinder". # # hub: http://smithlab.usc.edu/trackdata/methylation/hub.txt # file: http://smithlab.usc.edu/methbase/data/common/hg38/hg38.asm.bw # # We take the file as-is. No conversion, filtering or recalculation is done. mkdir -p /hive/data/genomes/hg38/bed/imprinting/methBaseAsm cd /hive/data/genomes/hg38/bed/imprinting/methBaseAsm curl -sS -O http://smithlab.usc.edu/methbase/data/common/hg38/hg38.asm.bw # The upstream file was last modified 2025-07-14 and is 163,160,098 bytes. # Sanity checks: hg38 chrom names and sizes, value range, coverage. bigWigInfo hg38.asm.bw # chromCount: 25 # basesCovered: 29,401,795 # mean: 0.000728 # min: 0.000000 # max: 0.862512 # std: 0.009708 # 25 chroms = chr1-chr22, chrX, chrY, chrM, all with hg38 sizes. All values are # fractions in [0,1]. basesCovered equals the number of annotated CpG positions, # each a single-base interval. Nothing is outside a chrom boundary, nothing was # skipped. # Spot check three loci: the H19/IGF2 imprinting control region, the # SNRPN/PWS-AS region, and a non-imprinted control region on chr20. for r in "chr11 1990000 2010000" "chr15 24954000 25200000" "chr20 57414000 57430000"; do set -- $r echo "== $1:$2-$3" bigWigToBedGraph -chrom=$1 -start=$2 -end=$3 hg38.asm.bw stdout \ | sort -k4,4gr | head -3 done # chr11:1,999,937 0.4886 <- H19 ICR, as expected # chr15:24,955,342 0.5362 <- SNRPN/MAGEL2 region, as expected # chr20:57,428,788 0.0006 <- control, essentially zero ############################################################################## # Geneimprint - catalog of imprinted and candidate imprinted genes # (refs #37599) ############################################################################## # Geneimprint (https://geneimprint.com, curated by Randy L. Jirtle) publishes a # table of imprinted and candidate imprinted genes per species. The human table # gives a cytogenetic band but no coordinates, so the gene symbols have to be # resolved against a gene annotation. We use the HGNC track, which carries the # approved symbol, the previous approved symbols, the alias symbols and the # cytogenetic band of every locus. mkdir -p /hive/data/genomes/hg38/bed/imprinting/geneimprint cd /hive/data/genomes/hg38/bed/imprinting/geneimprint curl -sSL -A "Mozilla/5.0" \ "https://geneimprint.com/site/genes-by-species.Homo+sapiens" \ -o geneimprint.human.html # the two annotations the symbols are resolved against bigBedToBed /gbdb/hg38/hgnc/hgnc.bb hgnc.bed hgsql hg38 -N -e "select chrom,txStart,txEnd,strand,name2 from refGene" > refGene.tsv # parse the table, resolve the symbols, write bed9+9 plus a report ~/kent/src/hg/makeDb/scripts/imprinting/geneimprintToBed.py \ geneimprint.human.html hgnc.bed refGene.tsv \ geneimprint.bed geneimprint.report.txt # 281 rows in the catalog, 274 features written: # 4 rows dropped, their identifiers are retired and match nothing in HGNC or # refGene (ZNF127AS, PWCR1, LOC100131170, FLJ20464). PWCR1 is the old name # of the SNORD116 cluster, which is in the track under that name. # 3 genes are listed twice in the catalog under a current and a retired # symbol (FBRSL1/KIAA1545, ISM1/C20orf82, MRAP2/C6orf117); each pair is # merged into one feature carrying both names. # Mapping checks in the report: all 274 loci fall on the chromosome arm the # catalog states, and 273 of 274 agree with the catalog's antisense marker on # the strand (ZDBF2 is the exception). bedToBigBed -type=bed9+9 -tab \ -as=$HOME/kent/src/hg/makeDb/scripts/imprinting/geneimprint.as \ -extraIndex=name \ geneimprint.bed /hive/data/genomes/hg38/chrom.sizes geneimprint.bb # spot check the canonical loci bigBedToBed geneimprint.bb stdout \ | grep -wE "H19|IGF2|KCNQ1OT1|SNRPN|UBE3A|MEG3|GNAS|PLAGL1" | cut -f1-4,10,11 # H19 maternal, IGF2 paternal, KCNQ1OT1 paternal, SNRPN paternal, # UBE3A maternal, MEG3 maternal, GNAS isoform dependent, PLAGL1 paternal ############################################################################## # Akbari iDMRs - imprinted differentially methylated regions # (refs #37599) ############################################################################## # Akbari et al. 2023 (Cell Genomics, PMID 36777186) assembled 192 imprinted # DMRs on the autosomes from five earlier genome-wide studies, for their PatMat # parent-of-origin method. The list is table S3 of the paper and is also # shipped with PatMat as Imprinted_DMR_List_V1.GRCh38.tsv. # # tableS3.tsv was downloaded by hand from the paper's supplementary material. cd /hive/data/genomes/hg38/bed/imprinting/akbari2023 # confirm the supplementary table and the tool's own copy hold the same regions curl -sSL \ "https://raw.githubusercontent.com/vahidAK/PatMat/main/patmat/Imprinted_DMR_List_V1.GRCh38.tsv" \ -o patmat.Imprinted_DMR_List_V1.GRCh38.tsv awk -F'\t' 'NR>1{print $1"\t"$2"\t"$3}' tableS3.tsv | sort > /tmp/s3.coords awk -F'\t' 'NR>1{print $1"\t"$2"\t"$3}' patmat.Imprinted_DMR_List_V1.GRCh38.tsv \ | sort > /tmp/pm.coords comm -12 /tmp/s3.coords /tmp/pm.coords | wc -l # 192, i.e. all of them, the two copies are identical # IMPORTANT: the published Start column is 1-based inclusive, not BED. PatMat's # own reader does "dmr_start = int(line[1]) - 1" before handing the interval to # tabix (patmat/core/methylation.py, process_dmr_line), which settles it. The # converter below applies that shift. ~/kent/src/hg/makeDb/scripts/imprinting/akbariIdmrToBed.py \ tableS3.tsv /hive/data/genomes/hg38/chrom.sizes \ akbariIdmr.bed akbariIdmr.report.txt # 192 rows in, 192 features out, nothing skipped. 144 maternally methylated and # 48 paternally methylated; 93 regions reported by two or more studies and 99 by # a single study, which matches the counts stated in the paper. Region length # 64 bp to 44,308 bp, median 867 bp, 414,958 bp in total. One region (H19) has # NA in the six WGBS validation columns, so those are stored as empty strings # and hidden on the details page with skipEmptyFields. bedToBigBed -type=bed9+11 -tab \ -as=$HOME/kent/src/hg/makeDb/scripts/imprinting/akbariIdmr.as \ -extraIndex=name,gene \ akbariIdmr.bed /hive/data/genomes/hg38/chrom.sizes akbariIdmr.bb # spot check the canonical imprinting control regions and their methylated allele bigBedToBed akbariIdmr.bb stdout | awk -F'\t' '$1=="chr11"' | cut -f1-4,10 # H19 paternal, IGF2_DMR2 paternal, IGF2_DMR0 paternal, KvDMR1 maternal # cross-check against the MethBase2 ASM subtrack: the two chr11 ASM peaks sit # on the H19 region and on KvDMR1, and the chr15 peak sits inside the # SNRPN region ############################################################################## # OMIM Imprinted - genes flagged as imprinted in the OMIM gene map # (refs #37599) ############################################################################## # The OMIM staff curate imprinting from the primary literature, but that call is # published only through GeneScout, which appends "(I)" to the coordinates in its # Location column. It is NOT part of the OMIM gene map and NOT in any of the # licensed OMIM download files: today's genemap.txt, genemap2.txt and # morbidmap.txt contain zero occurrences of "(I)". # # grep -c "(I)" /hive/data/outside/otto/omim/2026-09-03/genemap{,2}.txt # 0 # 0 # # So the flag has to come from a GeneScout export, which is also the only input # the converter needs. # # MANUAL STEP - Max did this by hand in a web browser, and it cannot be # automated. genescout.omim.org sits behind a Cloudflare JavaScript challenge # that returns HTTP 403 to curl and wget for every path on the host, so the file # cannot be fetched from hgwdev. To repeat it: # # 1. open https://genescout.omim.org/ in a browser # 2. set assembly GRCh38 (hg38), operation "intersect" # 3. paste one whole-chromosome interval per line into Primary coordinates, # chr1:1-248956422 through chrY:1-59373566, using the hg38 chrom.sizes # lengths # 4. run the search, then Download the results table as tab-delimited # 5. copy the file to the data directory below # # The export used here was generated 2026-09-03 and saved as # GeneScout-Results.tsv. It has a 76-line preamble; the results header is on # line 77 and the converter locates it by looking for the header row rather than # by a fixed offset. cd /hive/data/genomes/hg38/bed/imprinting/omimImprint # GeneScout-Results.tsv placed here by hand, see above ~/kent/src/hg/makeDb/scripts/imprinting/omimImprintToBed.py \ GeneScout-Results.tsv /hive/data/genomes/hg38/chrom.sizes \ omimImprint.bed omimImprint.report.txt # 44,566 gene rows in the export, 567 of them carry the (I) marker, 459 features # written: # 225 have an OMIM gene entry of their own # 234 are in the gene map without one, mostly antisense transcripts, lncRNAs # and microRNAs inside imprinted clusters (KCNQ1-AS1, INS-IGF2, ...) # 108 dropped: these are OMIM phenotype entries, not genes. They are mapped # disease regions and coarse linkage intervals running up to 90 Mb (SRS2 # chr7, 89.6 Mb; DEL18q, 61.9 Mb; DEL9p, 43.0 Mb) and would blanket the # display. All 108 are listed in omimImprint.report.txt. Phenotype # positions are already in the omimLocation track. # # The script needs nothing but the export: a phenotype entry repeats the same # MIM number in the Gene MIM# and Phenotype MIM# columns, while a gene entry # carries two different numbers. That rule was checked against OMIM's own # mimTitles.txt prefixes ("Number Sign"/"Percent" = phenotype) and agrees on all # 567 flagged entries, 0 disagreements, so no OMIM download file is needed. # # The coordinates were also checked once against the licensed genemap2.txt: all # 225 flagged loci that have an OMIM gene entry agreed exactly, 0 disagreements # on chromosome, start or end. That was a one-off validation, the build does not # depend on it. # # GeneScout coordinates are 1-based inclusive, so the start is decremented by # one. Established two ways: the export echoes whole chromosomes as # "chr1:1-248,956,422" (a 0-based system would start at 0), and comparing # genemap2.txt against the 0-based hgnc.bb over 17,617 genes gives a modal # start difference of exactly +1 and end difference of exactly 0. # # genemap2.txt is then used as an independent coordinate check: all 225 loci # with an OMIM gene entry agree with the licensed gene map exactly, 0 # disagreements on chromosome, start or end. bedToBigBed -type=bed9+6 -tab \ -as=$HOME/kent/src/hg/makeDb/scripts/imprinting/omimImprint.as \ -extraIndex=name \ omimImprint.bed /hive/data/genomes/hg38/chrom.sizes omimImprint.bb +# The OMIM curators confirmed that the (I) marker covers both established and +# candidate imprinted genes, and that the export gives no way to tell the two +# apart. The track labels and the description page say so; do not present these +# genes as settled imprinting calls. + # Check that the (I) marker really means imprinted, rather than being one of # GeneScout's display markers like the (S) that flags a gene spanning the edge # of a search interval. Compare the flagged loci with the two other subtracks, # against a size-matched random sample of unflagged genes as the baseline. cd /hive/data/genomes/hg38/bed/imprinting bedtools intersect -a omimImprint/omimImprint.bed -b akbari2023/akbariIdmr.bed -u | wc -l bedtools intersect -a omimImprint/omimImprint.bed -b geneimprint/geneimprint.bed -u | wc -l # 148 of the flagged loci overlap an Akbari iDMR and 303 overlap a Geneimprint # gene. For 529 randomly chosen genes that do NOT carry the marker the same two # counts are 0 and 5. The marker is also per gene, not per band: 11p15.5 has 13 # of its 129 genes flagged. # # No redistribution restriction applies: this track is built purely from the # GeneScout export and contains no OMIM download data, so unlike omimGene2 it # needs no "tableBrowser noGenome".