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The V(D)J recombination forms the immunoglobulin genes by joining thevariable (V), diversity (D), and joining (J) germline genes. Since variationsin germline genes have been linked to various diseases, personalizedimmunogenomics aims at finding alleles of germline genes across variouspatients. Although recent studies described algorithms for de novo inference ofV and J genes from immunosequencing data, they stopped short of solving a moredifficult problem of reconstructing D genes that form the highly divergent CDR3regions and provide the most important contribution to the antigen binding. Wepresent the IgScout algorithm for de novo D gene reconstruction and apply it toreveal new alleles of human D genes and previously unknown D genes in camel, animportant model organism in immunology. We further analyze non-canonical V(DD)Jrecombination that results in unusually long tandem CDR3s and thus expands thediversity of the antibody repertoires. We demonstrate that tandem CDR3srepresent a consistent and functional feature of all analyzed immunosequencingdatasets, reveal ultra-long tandem CDR3s, and shed light on the mechanismresponsible for their formation.

De novo inference of diversity genes and analysis of non-canonical V(DD)J recombination in immunoglobulins