2019/01/08 by Yana Safonova, Pavel A. Pevzner, Safonova, Yana +1
Immunology and Microbiology · Medicine · #T-cell and B-cell Immunology #Monoclonal and Polyclonal Antibodies Research #Immune Cell Function and Interaction
paper · pdf · doi:10.48550/arxiv.1901.02483
The V(D)J recombination forms the immunoglobulin genes by joining the\nvariable (V), diversity (D), and joining (J) germline genes. Since variations\nin germline genes have been linked to various diseases, personalized\nimmunogenomics aims at finding alleles of germline genes across various\npatients. Although recent studies described algorithms for de novo inference of\nV and J genes from immunosequencing data, they stopped short of solving a more\ndifficult problem of reconstructing D genes that form the highly divergent CDR3\nregions and provide the most important contribution to the antigen binding. We\npresent the IgScout algorithm for de novo D gene reconstruction and apply it to\nreveal new alleles of human D genes and previously unknown D genes in camel, an\nimportant model organism in immunology. We further analyze non-canonical V(DD)J\nrecombination that results in unusually long tandem CDR3s and thus expands the\ndiversity of the antibody repertoires. We demonstrate that tandem CDR3s\nrepresent a consistent and functional feature of all analyzed immunosequencing\ndatasets, reveal ultra-long tandem CDR3s, and shed light on the mechanism\nresponsible for their formation.\n