Resolving HLA haplotypes with long-read capture

At PacBio PRISM, Dr. Omar Cornejo of UC Santa Cruz details an efficient long-read hybrid capture method designed to resolve complex Human Leukocyte Antigen (HLA) haplotypes. This approach addresses the significant challenges posed by the extreme polymorphism and structural complexity of the HLA region, which have traditionally hindered accurate characterization with short-read technologies.

Dr. Cornejo explains how this method, developed with Twist Bioscience, enables comprehensive analysis of the entire HLA region, including the often-neglected class three genes. The presentation highlights key performance metrics using PacBio long reads, demonstrating high on-target enrichment and excellent genotype concordance, with over 99% accuracy for SNVs. This high-fidelity data allows for the assembly of complete and accurate haplotypes, overcoming issues like reference bias. To fully leverage these results, the team developed HLA-Resolve, a new tool for correctly assigning allele nomenclature from long-read data. Dr. Cornejo concludes by outlining a path to increase the method's affordability, enhancing its utility for large-scale studies.

00:00 Introduction
01:21 The importance of the HLA region
03:42 Polymorphism and sequencing challenges
07:46 The evolutionary complexity of HLA genes
10:18 A new long-read capture method
12:16 Method performance: coverage and read length
15:50 Genotype and haplotype accuracy with PacBio
18:34 Identifying alleles and the need for new tools
21:02 HLA-Resolve: a tool for long-read haplotypes
21:25 Future directions and cost reduction

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