This track shows gene annotations mapped onto this Human Pangenome Reference Consortium (HPRC) Release 2 assembly with Liftoff. Genes are the stretches of DNA that are copied into RNA and, for most of them, translated into protein. Liftoff takes an existing, curated set of genes from a reference genome and finds the matching location of each one in the new assembly, so that familiar RefSeq gene models can be viewed directly in each individual's genome. Because it maps genes one by one rather than re-predicting them, Liftoff is well suited to transferring a trusted reference annotation with its original names and identifiers.
Genes follow the standard UCSC gene display: boxes are exons, connecting lines are introns, and arrows on the introns show the direction of transcription. Thicker boxes mark the coding portion (CDS) and thinner boxes the untranslated regions. When zoomed in, the amino-acid translation and the underlying bases can be shown. Items are labeled by gene name; the transcript accession (a RefSeq NM_, NR_, XM_ or XR_ identifier) and the gene and transcript biotypes appear on the details page. Gene name and transcript accession are both searchable. Liftoff can place more than one copy of a gene, so some genes appear as several models. The accession of a transcript sometimes carries a trailing _1 or similar suffix, which Liftoff and the source annotation use to keep the identifiers of such repeated placements distinct.
Liftoff aligns the transcript sequences of a reference annotation to the target assembly with minimap2 and then chooses, for each gene, the mapping that best preserves its exon-intron structure, optionally identifying additional gene copies. See the reference below for details. For the HPRC pangenome, the human RefSeq annotation (via the CHM13 reference) was lifted onto each assembly.
The annotation files were obtained from the HPRC Release 2 data collection on the public s3://human-pangenomics bucket, indexed at the hprc_intermediate_assembly data tables. Each per-assembly GFF3 was converted to a UCSC bigGenePred file. The Liftoff GFF3 does not record CDS phase, so the phase of each coding exon was recomputed before conversion with gff3ToGenePred and genePredToBigGenePred. The steps are described in the -makeDoc, +makeDoc, the build scripts are in the kent source tree, and the track configuration is in trackDb/contrib/hprc2annot. Roughly one transcript in ten thousand is missing from the track. These are models whose exons Liftoff placed at coordinates that contradict each other, for example a transcript whose recorded start lies after its recorded end, or exons that overlap one another. Such a model cannot be expressed as a gene prediction and is dropped rather than repaired; the counts are recorded per assembly in the build log.
For automated analysis, the annotation is stored in a bigBed-format file (liftoffGenes.bb) that can be read with the UCSC tool bigBedToBed, which can be compiled from source or downloaded as a precompiled binary. It can also extract features for a region. The original annotation files are available from the HPRC S3 bucket linked above.
Annotations were generated by the Human Pangenome Reference Consortium. Thanks to the HPRC production team for making these data available.
Shumate A, Salzberg SL. Liftoff: accurate mapping of gene annotations. Bioinformatics. 2021 Jul 19;37(12):1639-1643. PMID: 33320174; PMC: PMC8289374