Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR

• DOI: 10.1101/gr.278775.123
• Publication Date: 2024-10-21T20:10:12Z
• Authors: Artem Mikelov; George Nefediev; Alexander Tashkeev; Oscar L. Rodriguez; Diego Aguilar Ort...; Valeriia Skatova; Mark Izraelson; Alexey N. Davydov; Stanislav Poslavsky; Souad Rahmouni; Corey T. Watson; Dmitriy Chudakov; Scott D. Boyd; Dmitry Bolotin
• Keywords: Methods; 3. Good health

Allelic variability in the adaptive immune receptor loci, which harbor gene segments that encode B cell and T receptors (BCR/TCR), is of critical importance for responses to pathogens vaccines. Adaptive repertoire sequencing (AIRR-seq) has become widespread immunology research making it most readily available source information about allelic diversity immunoglobulin (IG) (TR) loci. Here we present a novel algorithm extra-sensitive specific variable (V) joining (J) allele inference, allowing reconstruction individual high-quality segment libraries. The approach can be applied inferring variants from peripheral blood lymphocyte BCR TCR data, including hypermutated isotype-switched sequences, thus high-throughput discovery wide variety existing datasets. developed part MiXCR software. We demonstrate accuracy this using AIRR-seq paired with long-read genomic comparing widely used algorithm, TIgGER. large set IG heavy chain ( IGH ) data 450 donors ancestrally diverse population groups, largest reported full-length alpha beta (TRA; TRB) dataset, representing 134 individuals. This allowed us assess genetic within , TRA TRB loci different populations establish database alleles V J genes inferred their frequencies free public access through an online database.