Personalized HLA typing leads to the discovery of novel HLA alleles and tumor‐specific HLA variants

Abstract

Funding information Norges ForskningsrådAccurate and full-length typing of the HLA region is important in many clinical and research settings. With the advent of next generation sequencing (NGS), several HLA typing algorithms have been developed, including many that are applicable to whole exome sequencing (WES). However, most of these solutions operate by providing the closest-matched HLA allele among the known alleles in IPD-IMGT/HLA Database. These database-matching approaches have demonstrated very high performance when typing well characterized HLA alleles. However, as they rely on the completeness of the HLA database, they are not optimal for detecting novel or less well characterized alleles. Furthermore, the database-matching approaches are also not adequate

A pan-MHC reference graph with 246 fully contiguous phased sequences

“…The IMGT/HLA database 17 , a public repository for known HLA allele sequences, can be used as a reference for HLA genotyping; however, a pre-existent database of alleles might not always allow the discovery of new alleles, nor can it easily identify haplotypes or intergenic variation. Custom bioinformatic methods exist to discover novel HLA alleles using short reads 27,28 , but throughput and phasing remain challenging. To solve the problem of phasing, dense genotyping arrays have been used to construct large population-specific reference panels and quantify LD 29,30 , but this approach is expensive and only applicable to one population at a time.…”