HLA typing using targeted third-generation sequencing methods

Abstract

Detailed typing of the extremely variable human leukocyte antigens (HLA) is necessary to check for transplantation compatibility and to investigate auto-immune disorders. Nanopore sequencing allows detailed typing with reduced levels of sequencing artefacts, costs, and workload. The longer reads also reduce the complexity of the downstream data analysis. On top of that, targeted sequencing strategies for nanopore sequencing allows specific enrichment of long reads in the different HLA regions without using PCR. Two approaches of targeted sequencing were demonstrated to yield major advantages for HLA typing: CRISPR/Cas9 enrichment and adaptive sampling.