Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles
Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles
Significance High-throughput sequencing of B-cell immunoglobulin receptors is providing unprecedented insight into adaptive immunity. A key step in analyzing these data involves assignment of the germline variable (V), diversity (D), and joining (J) gene-segment alleles that comprise each immunoglobulin sequence by matching them against a database of known V(D)J alleles. However, this process will fail for sequences that use previously undetected alleles, whose frequency in the population is unclear. Here we describe TIgGER, a computational method that significantly improves V(D)J allele assignments by first determining the complete set of gene segments carried by a subject, including novel alleles. The application of TIgGER identifies a surprisingly high frequency of novel alleles, highlighting the critical need for this approach.
- Yale University United States
- Bar-Ilan University Israel
B-Lymphocytes, Polymorphism, Genetic, Base Sequence, Genes, Immunoglobulin, Genotype, Immunoglobulin Variable Region, High-Throughput Nucleotide Sequencing, V(D)J Recombination, Automation, Mutation Rate, Databases, Genetic, Mutation, Humans, Gene Rearrangement, B-Lymphocyte, Alleles, Software
B-Lymphocytes, Polymorphism, Genetic, Base Sequence, Genes, Immunoglobulin, Genotype, Immunoglobulin Variable Region, High-Throughput Nucleotide Sequencing, V(D)J Recombination, Automation, Mutation Rate, Databases, Genetic, Mutation, Humans, Gene Rearrangement, B-Lymphocyte, Alleles, Software
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