Development and validation of a pipeline for the systematic search for new HLA alleles in WGS data

Background: Human leukocyte antigen (HLA) is a highly polymorphic locus in the human genome that also has high clinical significance. New alleles of HLA genes are constantly being discovered but mostly by HLA typing laboratories using field-specific protocols, such as enrichment of the HLA region in high-throughput sequencing data. Nevertheless, a vast amount of whole-genome sequencing (WGS) data has been accumulated over the past years. The main goal of our work was to develop and validate a pipeline specifically tailored toward the identification and characterization of new HLA alleles from 30x WGS sequencing. Results: ) typed by HLA-HD and discovered 17 potentially new HLA alleles with substitutions in exonic regions. We further validated five of these alleles using Sanger sequencing and submitted them to the IPD-IMGT/HLA database. Conclusion: HLAchecker is suitable for the identification of new HLA alleles in large WGS cohorts accumulated by the scientific community in recent years. HLAchecker is freely available at https://gitlab.com/EugeneA/hlachecker.