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Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

Authors: Daniel, Gadala-Maria; Gur, Yaari; Mohamed, Uduman; Steven H, Kleinstein;

Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

Abstract

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.

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Keywords

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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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    191
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
191
Top 1%
Top 10%
Top 1%
bronze