ef779a5a2ed508cb00f0b0139a12d696e439ee5f max Fri Sep 11 06:06:55 2026 -0700 new hg38 track hprcRdt: reference-divergent transcripts from 206 HPRC Release 2 genomes Added as a third child of the existing long_read_transcripts superTrack, alpha only for now. Data from Max Marin (DFCI), a bigPsl of RDT cluster representative sequences aligned to GRCh38: 180,464 alignments of 120,451 distinct sequences from 412 haplotypes. Rebuilt from the submitted file only to add a name index, refs #33822 diff --git src/hg/makeDb/trackDb/human/hg38/hprcRdt.html src/hg/makeDb/trackDb/human/hg38/hprcRdt.html new file mode 100644 index 00000000000..e68a96b3e11 --- /dev/null +++ src/hg/makeDb/trackDb/human/hg38/hprcRdt.html @@ -0,0 +1,134 @@ +<h2>Description</h2> + +<p> +This track is part of the +<a href="hgTrackUi?hgsid=${hgsid}&g=long_read_transcripts">Long-read Transcripts</a> +collection. +</p> + +<p> +It shows reference-divergent transcripts (RDTs) found in the genomes of the +Human Pangenome Reference Consortium (HPRC), aligned back onto GRCh38. An RDT is +a transcript that was sequenced and assembled in one of these genomes but that +does not match the GRCh38 gene annotation well, either because it uses splice +sites or exons that the reference annotation does not have, or because it comes +from a region where the donor genome differs from the reference. Transcripts +like these are invisible to an analysis that maps reads only against GRCh38, so +they are one way of measuring how much of human transcript diversity a single +reference genome misses. +</p> + +<p> +The track holds about 180,000 alignments of roughly 120,000 distinct transcript +sequences, drawn from 412 haplotype assemblies of 206 individuals. Alignments +are far from evenly spread. Around 40% of them fall in two places: the MHC +class I region on chr6 and the immunoglobulin heavy chain locus on chr14. Both +are among the most polymorphic loci in the genome, so a reference-based +annotation is expected to describe them poorly. +</p> + +<h2>Display Conventions and Configuration</h2> + +<p> +Each item is the alignment of one transcript sequence to GRCh38. Blocks are +aligned segments, thin connecting lines with arrows are the gaps between them, +and the arrows give the strand the transcript aligns to. Because these are +alignments rather than gene models, the display also marks where the transcript +and the reference disagree: an orange line marks bases that the transcript has +in the middle of the alignment but the reference does not, a purple line marks +the same at either end of the transcript, and a pair of horizontal lines marks a +place where both sequences have an insertion relative to the other. These +markers can be turned off in the track configuration. +</p> + +<p> +The item name is the identifier of the transcript in its source haplotype, so it +carries the sample name, the haplotype, and the PacBio locus and isoform number, +for example <tt>G_PBKT.HG01960_Hap1_PB.104.1</tt>. Names can be typed into the +position box to jump to a transcript. The same transcript can align in more than +one place, so a name can match several positions and the position box then +offers a list. +</p> + +<p> +Where the alignments are too dense to tell apart, the track switches by itself to +a coverage graph. In the most crowded parts of the MHC this happens in a window +of only a few kilobases; elsewhere it happens once the window passes 200 kbp. +</p> + +<h2>Methods</h2> + +<p> +Full-length RNA of 206 HPRC Release 2 samples was sequenced with the PacBio +<a href="https://www.pacb.com/technology/kinnex/" target="_blank">Kinnex</a> +protocol. For each sample, transcripts were assembled and annotated against that +sample's own two haplotype assemblies rather than against GRCh38, giving 412 +per-haplotype transcript annotations. Each transcript was compared to the +reference annotation lifted onto the haplotype with +<a href="https://github.com/agshumate/Liftoff" target="_blank">Liftoff</a> and +classified with +<a href="https://ccb.jhu.edu/software/stringtie/gffcompare.shtml" target="_blank">gffcompare</a>, +and coding potential was assessed with +<a href="https://github.com/alevar/ORFanage" target="_blank">ORFanage</a>. +Transcripts that diverged from the reference annotation were kept as RDTs. The +RDT sequences from all haplotypes were then clustered at 99% sequence identity +and 99% coverage, and one representative sequence per cluster was aligned back +to GRCh38 to produce this track. The per-haplotype annotations themselves, which +carry the gene assignment, gffcompare class code, read support and ORF calls for +every transcript, are available as a track hub on the individual HPRC assemblies +(see the repository linked below). +</p> + +<p> +The alignment file was downloaded from +<a href="https://github.com/maxgmarin/hprc-r2-rdt-testhub" target="_blank">https://github.com/maxgmarin/hprc-r2-rdt-testhub</a>, +file <tt>Data/HPRC.PanTx.ClusteredRDTsRepSeqs.SID99C99.AlnToHG38.bb</tt>. At +UCSC it was converted back to text, checked against the GRCh38 chromosome sizes, +and rebuilt as a bigBed with an index on the transcript name so that names can be +searched. No alignments were added or dropped: the 180,464 alignments in the +source file are all present in the track. Note that the source file records no +mismatch counts, so the per-alignment details page reports every alignment as +100% identity regardless of how much the transcript actually diverges from +GRCh38. The commands used are in the +<a href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/hprcRdt.txt" target="_blank">makeDoc</a>, +and the build script is in the +<a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/scripts/hprcRdt" target="_blank">kent source tree</a>. +</p> + +<h2>Data Access</h2> + +<p> +The data can be explored interactively in table format with the +<a href="../cgi-bin/hgTables">Table Browser</a> or the +<a href="../cgi-bin/hgIntegrator">Data Integrator</a> and exported from there to +spreadsheet or tab-sep tables. From scripts, the data can be accessed through our +<a href="https://api.genome.ucsc.edu">API</a>, track=<i>hprcRdt</i>. +</p> + +<p> +For automated download and analysis, the genome annotation is stored in a bigBed +file that can be downloaded from +<a href="http://hgdownload.soe.ucsc.edu/gbdb/hg38/hprcRdt/" target="_blank">our +download server</a>. The file for this track is called <tt>hprcRdt.bb</tt>. +Individual regions or the whole genome annotation can be obtained using our tool +<tt>bigBedToBed</tt>, which can be compiled from the source code or downloaded as +a precompiled binary for your system. Instructions for downloading source code and +binaries can be found +<a href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads">here</a>. +The tool can also be used to obtain features within a given range, e.g. +<tt>bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/hprcRdt/hprcRdt.bb -chrom=chr21 -start=0 -end=100000000 stdout</tt> +</p> + +<p> +The original annotation source data can be downloaded from +<a href="https://github.com/maxgmarin/hprc-r2-rdt-testhub" target="_blank">https://github.com/maxgmarin/hprc-r2-rdt-testhub</a>. +</p> + +<h2>Credits</h2> + +<p> +Thanks to Max Marin at the Dana-Farber Cancer Institute for producing this +annotation and making it available, and to the +<a href="https://humanpangenome.org/" target="_blank">Human Pangenome Reference +Consortium</a> for the assemblies and the sequencing data. +</p>