bioRxiv Science⌕ Search

Biology subjects

Albracht, D.

Publications and source records attributed to Albracht, D..

2 recordsLinked to original sources
bioRxiv2026

HPRC2: A human pangenome reference with near-complete coverage of common genetic variation

A pangenome reference overcomes the inherent limitation of any individual reference genome by integrating the variation present in a population. We present the Human Pangenome Reference Consortiums (HPRC) Release 2 (HPRC2), an openly available, second phase pangenome that is an approximately fivefold expansion in genome number over HPRC Release 1 (HPRC1) and measurable improvement in genome completeness, contiguity, and accuracy. Selecting samples with a principled algorithm prioritising common variant coverage, HPRC2 contributes 460 haplotypes that together capture over 99% of common variation observed in the All of Us Research Program v8 cohort. Combining high-coverage long and ultra-long reads with modern assemblers and polishers, we produce thousands of telomere-to-telomere (T2T) chromosomes, and relative to HPRC1 halve the number of structurally unreliable regions as well as individual base errors per haplotype. We complement the assemblies with whole genome multiple alignments and gene annotations, and derive formal pangenome coordinate systems for addressing off-reference variation, demonstrating that individual human genomes contain more than one hundred thousand variants not succinctly described with respect to existing reference genomes. We also present the first matched long-read backed pantranscriptome and panepigenome at this scale, provide continuous local-ancestry estimates spanning every genome, and outline a host of new tools and applications that leverage the pangenome resource for improved genomics analysis.

genomics↗
bioRxiv2026

Leveraging Human Pangenome for Improved Somatic Variant Detection

Somatic variant detection is technically challenging due to low variant allele fractions, the confounding presence of germline variation, and reference bias. Linear references such as GRCh38 miss sample-specific variation, causing misalignments and incorrect variant calls. Although telomere-to-telomere donor-specific assemblies (DSAs) accurately represent individual genomes, their application is limited by cost and technical barriers. Alternatively, the graph-based human pangenome provides a scalable framework to improve read alignment and perform genome inference. Here, we benchmarked somatic variant detection using GRCh38, graph-based pangenomes, and pangenome-inferred DSAs with a HapMap mixture dataset and the COLO829 melanoma cell line. Pangenome-guided alignment improves read mapping and somatic variant calling accuracy. Furthermore, personalized pangenomes partially reconstruct donor-specific genomic content, improving accuracy, reducing germline contamination, and enabling detection of events in loci absent or poorly represented in GRCh38. These findings demonstrate that graph-based and personalized pangenomes are effective strategies for enhancing somatic variant detection compared with GRCh38.

genomics↗