Easy-HLA: a validated web application suite to reveal the full details of HLA typing

Motivation: The HLA system plays a pivotal role in both clinical applications and immunology research. Typing HLA genes in patient and donor is indeed required in hematopoietic stem cell and solid-organ transplantation, and the histocompatibility complex region exhibits countless genetic associations with immune-related pathologies. Since the discovery of HLA antigens, the HLA system nomenclature and typing methods have constantly evolved, which leads to difficulties in using data generated with older methodologies. Results: Here, we present Easy-HLA, a web-based software suite designed to facilitate analysis and gain knowledge from HLA typing, regardless of nomenclature or typing method. Easy-HLA implements a computational and statistical method of HLA haplotypes inference based on published reference populations containing over 600 000 haplotypes to upgrade missing or partial HLA information: 'HLA-Upgrade' tool infers high-resolution HLA typing and 'HLA-2-Haplo' imputes haplotype pairs and provides additional functional annotations (e.g. amino acids and KIR ligands). We validated both tools using two independent cohorts (total n=2500). For HLA-Upgrade, we reached a prediction accuracy of 92% from low- to high-resolution of European genotypes. We observed a 96% call rate and 76% accuracy with HLA-2-Haplo European haplotype pairs prediction. In conclusion, Easy-HLA tools facilitate large-scale immunogenetic analysis and promotes the multi-faceted HLA expertise beyond allelic associations by providing new functional immunogenomics parameters.