IGHV allele similarity clustering improves genotype inference from adaptive immune receptor repertoire sequencing data

Abstract

In adaptive immune receptor repertoire analysis, determining the germline variable (V) allele associated with each T- and B-cell receptor sequence is a crucial step. This process is highly impacted by allele annotations. Aligning sequences, assigning them to specific germline alleles, and inferring individual genotypes are challenging when the repertoire is highly mutated, or sequence reads do not cover the whole V region. Here, we propose an alternative naming scheme for the V alleles as well as a novel method to infer individual genotypes. We demonstrate the strength of the two by comparing their outcomes to other genotype inference methods and validated the genotype approach with independent genomic long read data. The naming scheme is compatible with current annotation tools and pipelines. Analysis results can be converted from the proposed naming scheme to the nomenclature determined by the International Union of Immunological Societies (IUIS). Both the naming scheme and the genotype procedure are implemented in a freely available R package (PIgLET). To allow researchers to explore further the approach on real data and to adapt it for their future uses, we also created an interactive website (https://yaarilab.github.io/IGHV_reference_book).