  The V(D)J recombination forms the immunoglobulin genes by joining the
variable (V), diversity (D), and joining (J) germline genes. Since variations
in germline genes have been linked to various diseases, personalized
immunogenomics aims at finding alleles of germline genes across various
patients. Although recent studies described algorithms for de novo inference of
V and J genes from immunosequencing data, they stopped short of solving a more
difficult problem of reconstructing D genes that form the highly divergent CDR3
regions and provide the most important contribution to the antigen binding. We
present the IgScout algorithm for de novo D gene reconstruction and apply it to
reveal new alleles of human D genes and previously unknown D genes in camel, an
important model organism in immunology. We further analyze non-canonical V(DD)J
recombination that results in unusually long tandem CDR3s and thus expands the
diversity of the antibody repertoires. We demonstrate that tandem CDR3s
represent a consistent and functional feature of all analyzed immunosequencing
datasets, reveal ultra-long tandem CDR3s, and shed light on the mechanism
responsible for their formation.
