A long road/read to rapid high-resolution HLA typing: The nanopore perspective

Next-generation sequencing (NGS) has been widely adopted for clinical HLA typing and advanced immunogenetics researches. Current methodologies still face challenges in resolving cis-trans ambiguity involving distant variant positions, and the turnaround time is affected by testing volume and batching. Nanopore sequencing may become a promising addition to the existing options for HLA typing. The technology delivered by the MinION sequencer of Oxford Nanopore Technologies (ONT) can record the ionic current changes during the translocation of DNA/RNA strands through transmembrane pores and translate the signals to sequence reads. It features simple and flexible library preparations, long sequencing reads, portable and affordable sequencing devices, and rapid, real-time sequencing. However, the error rate of the sequencing reads is high and remains a hurdle for its broad application. This review article will provide a brief overview of this technology and then focus on the opportunities and challenges of using nanopore sequencing for high-resolution HLA typing and immunogenetics research.