HLA-Resolve: High-Resolution HLA Haplotyping Using Long-Read Hybrid Capture
Glasenapp, M. R.; Yee, M.-C.; Symons, A. E.; Cornejo, O. E.; Garcia, O. A.
Show abstract
Accurate HLA typing is critical for transplantation, pharmacogenomics, and disease risk prediction, yet short-read approaches cannot resolve the HLA region's extreme polymorphism. Long-read sequencing improves resolution, but its adoption has been limited by higher cost, reduced base accuracy, limited throughput, and reliance on long-range PCR. To overcome these limitations, we present a multiplexed long-read hybrid capture workflow for PacBio and Oxford Nanopore sequencing that enriches all classical HLA loci and the complete HLA Class III region. A single-step enzymatic fragmentation and barcoding strategy enables automated library prep. We also introduce HLA-Resolve, an HLA typing program optimized for HiFi reads, and validate workflow performance against the Genome in a Bottle, Human Pangenome Reference Consortium, and International Histocompatibility Working Group benchmarks using 32 geographically diverse samples. These advances offer a cost-effective approach for high-resolution HLA typing with clinical applicability and enable investigation of the role of HLA Class III variation in disease.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.