Human Leukocyte Antigen Genotyping and Expression Analysis with Nanopore Long-Read Sequencing

Human leukocyte antigen (HLA) typing plays a critical role in evaluating donor-recipient compatibility prior to hematopoietic cell transplantation (HCT) to minimize the risk of rejection and graft versus host disease (GVHD). Compared to traditional sequence-based methods for HLA typing, next-generation sequencing offers significant advantages in terms of accuracy, turnaround time, and cost. Here, we sought to evaluate the performance of nanopore long-read sequencing for HLA typing and HLA expression analysis, including the identification of HLA transcript isoforms. To that end, we used nanopore long-read sequencing to perform RNA-seq on primary lymphocytes isolated from peripheral blood from 12 human donors.