HPRC release 2 gene models, one transcript per gene per haplotype, for JBrowse 2 ================================================================================ A redistribution of HPRC and T2T data, not original data. Each ..genes.bed.gz but HG002's is that haplotype's CAT annotation from the release 2 index https://raw.githubusercontent.com/human-pangenomics/hprc_intermediate_assembly/main/data_tables/annotation/cat/cat_genes_hprc_r2_v1.3.index.csv reduced to one transcript per gene as BED12, with the gene name in the name column and the coding span as thickStart/thickEnd, sorted, bgzipped and tabix-indexed twice: a .tbi, and the .csi with 256 kb bins that JBrowse reads. Contig names are the assembly's own, as the annotation writes them. The rules, which read GENCODE v48 (https://ftp.ebi.ac.uk/pub/databases/gencode/Gencode_human/release_48/gencode.v48.annotation.gff3.gz), the release CAT projected: - A gene's model is the projection of its Ensembl canonical transcript (the GENCODE "Ensembl_canonical" tag on CAT's source_transcript), the one whose span is nearest the GRCh38 span where CAT projected it twice; failing that, the transcript with the longest coding sequence, then spliced length. - Genes with no symbol are dropped: those CAT names by an Ensembl gene id, and CAT's own novel genes. - Two coding genes whose models share most of their coding bases here, though their source transcripts lie apart on GRCh38, are one locus CAT projected two paralogs onto (GSTM1 onto GSTM2 where a haplotype lacks GSTM1, DRB5 onto DRB1). The converter keeps the gene whose source transcript's GRCh38 span the haplotype's walk crosses at the model, in the pangenome graph's walk file https://jbrowse.org/demos/hprc/hprc-v2.1-mc-grch38-f7.GRCh38.walks.gz. Where the walk crosses both spans there or neither, it keeps the gene with the better CAT alignment goodness (the GFF3 score column; CAT's default there counts as a full match). - Genes spanning over 5 Mb are dropped. Genes GRCh38's primary assembly lacks ------------------------------------- CAT projects GENCODE's primary-assembly annotation, so it gives no model to a gene that only GRCh38's alt contigs hold. website/generatePangenomeLocusGenes.ts adds one for each locus in website/src/components/pangenomeLocusGenes.ts: GSTT1 x214 (ENST00000612885.4 on KI270879.1), in the walk across chr22:24001001-24002700: 214 models in 214 of 462 haplotypes, median identity 99.90% LILRA3 x361 (ENST00000620589.4 on GL949746.1), in the walk across chr19:54296001-54298000: 361 models in 361 of 462 haplotypes, median identity 99.94% HLA-DRB1 x0 (ENST00000360004.6 on chr6, ENST00000399450.6 on GL000251.2, ENST00000444645.6 on GL000252.2, ENST00000437784.6 on GL000253.2, ENST00000328980.11 on GL000255.2, ENST00000419393.6 on GL000256.2), HLA-DRB3 x188 (ENST00000426847.3 on GL000250.2, ENST00000383126.8 on GL000251.2, ENST00000307137.12 on GL000255.2), HLA-DRB4 x127 (ENST00000411959.7 on GL000253.2, ENST00000457451.7 on GL000254.2, ENST00000411565.3 on GL000256.2), HLA-DRB5 x75 (ENST00000374975.4 on chr6), in the walk across chr6:32474001-32577000: 390 models in 390 of 462 haplotypes, median identity 100.00% - The window searched is the haplotype's stretch of the pangenome graph's walk across the GRCh38 span that holds the gene, or beside the insertion that does, read from the haplotype's HPRC release 2 assembly. - minimap2 -x splice:hq splices the gene's transcript onto that window. The transcript's exons come from GENCODE's alt-aware annotation https://ftp.ebi.ac.uk/pub/databases/gencode/Gencode_human/release_48/gencode.v48.chr_patch_hapl_scaff.annotation.gff3.gz and their bases from the contig at NCBI. The model's exons are the alignment's blocks between introns, and its coding span holds the CDS's aligned bases. - The candidate gene that aligns best names each copy, and the copy gets a model when that gene aligns at 95% identity or more over 90% of its transcript. The model replaces the CAT models of the gene's family that overlap it. What these miss, because CAT does: - A gene only GRCh38's alt contigs hold, outside the loci above, has no model of its own: KIR2DL2, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3 and KIR3DS1. A copy of one of them is labelled with whichever GRCh38 paralog CAT projected onto it. - An extra copy CAT calls a novel isoform of a neighbouring gene has no model: HG01346#1's second GSTM1 is a "GSTM2" putative_novel_isoform. HG002 ----- CAT does not annotate HG002, whose release 2 assembly is the T2T Q100 hg002v1.1 (haplotype 1 is hg002v1.1.pat, 2 is hg002v1.1.mat_MT). HG002.1 and HG002.2 are JHU's Liftoff annotation of that assembly, v0.6: https://s3-us-west-2.amazonaws.com/human-pangenomics/T2T/HG002/assemblies/annotation/JHULiftoff/v0.6/hg002.v1.1.loff.v0.6.{pat,mat}.gff.gz which lifts RefSeq v110 from T2T-CHM13 and adds extra copies that miniprot finds; see the README.txt there, https://github.com/marbl/HG002 and Hansen et al., A complete diploid human genome benchmark for personalized genomics, Cell 2026 (https://doi.org/10.1016/j.cell.2026.06.016). It omits chrM and the functional V(D)J gene segments; its V segment pseudogenes and C regions stay, and so do their models here. The rules match CAT's where the data allows: - A gene's model is its MANE Select transcript; failing that, the transcript with the longest coding sequence, then spliced length. - A transcript that runs past its gene row is passed over: on HG002.1 one of KLRC2's spans both tandem copies. - A gene row without transcripts (pseudogenes, V segment pseudogenes, C regions, rRNA), or whose only transcripts run past it, is one non-coding block over the gene. - Genes with no symbol are dropped: RefSeq's LOC placeholders and the few named by a transcript assembly id (XLOC_, TCONS_). So are RefSeq's gene clusters (gene_biotype "other": PCDHA@, UGT1A, TRB, IGL), which span their member genes, and genes spanning over 5 Mb. - Contigs drop Liftoff's _PATERNAL/_MATERNAL suffix, to match the assembly. - No paralog step: Liftoff places a gene once per locus, and the coding genes that overlap there are readthroughs and clustered genes that share exons on the reference too. - The loci above run as for every haplotype. Liftoff has GSTT1 and LILRA3 (miniprot's, coding exons only) but no HLA-DRB3, -DRB4 or -DRB5, since RefSeq places those on GRCh38's alt contigs. On HG002.1 Liftoff's HLA-DRB6 lies on the 3' exons of the DRB4 the locus step finds, which replaces it. HPRC and T2T data are released under CC0; see https://github.com/human-pangenomics/hpp_pangenome_resources for the release and its terms. Read by the haplotype lanes of https://jbrowse.org/pangenome/hprc-grch38/config.json. Rebuilt by website/pangenome-config/buildHprcGenes.sh in https://github.com/GMOD/jb2hubs with bgzip (htslib) 1.23.1, tabix (htslib) 1.23.1 and node v24.2.0. 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