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Detection and Analysis of Mammalian Immunoglobulin Genes

  • Author(s): Sirupurapu, Vikram
  • Advisor(s): Pevnzer, Pavel
  • et al.

The V(D)J recombination process selects and rearranges the variable (V), diversity (D), and joining (J) genes in the immunoglobulin loci (IG) and generates antibody repertoires which are responsible for the adaptive immune systems of an organism. Sequencing and annotation of the highly repetitive IG loci across various species and predicting the V, D, and J genes (IG genes) is critical for antibody engineering and analyzing the evolution of the adaptive immune system. However, since the standard gene finding algorithms are not suitable for predicting IG genes, they have been semi-manually annotated in very few model species, with accurate annotations limited to human, mouse, and cow genomes. Moreover, it remains unclear what regulatory signals trigger the highly uneven usage of various IG genes in antibody repertoires.

I developed the IGDetective algorithm for finding and annotating IG genes, benchmarked it on the three well-annotated IG loci, and applied it to mammalian species with the recently assembled IG loci sourced from the Vertebrate Genome Project (VGP) consortium. This analysis resulted in the first large collection of predicted IG genes across many species and enabled their biological analysis. I also addressed the problem of explaining what drives the usage of the IG genes by revealing the recombinant signal sequences that trigger the high/low usage of these genes.

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