TIgGER

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 V, D and 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 utilize previously undetected alleles, whose frequency in the population is unclear.

TIgGER is a computational method that significantly improves V(D)J allele assignments by first determining the complete set of gene segments carried by an individual (including novel alleles) from V(D)J-rearrange sequences. TIgGER can then infer a subject’s genotype from these sequences, and use this genotype to correct the initial V(D)J allele assignments.

The application of TIgGER continues to identify a surprisingly high frequency of novel alleles in humans, highlighting the critical need for this approach. (TIgGER, however, can and has been used with data from other species.)

Core Abilities

  • Detecting novel alleles
  • Inferring a subject’s genotype
  • Correcting preliminary allele calls

Required Input

  • A table of sequences from a single individual, with columns containing the following:
    • V(D)J-rearranged nucleotide sequence (in IMGT-gapped format)
    • Preliminary V allele calls
    • Preliminary J allele calls
    • Length of the junction region
  • Germline Ig sequences in IMGT-gapped fasta format (e.g., as those downloaded from IMGT/GENE-DB)

The former can be created through the use of IMGT/HighV-QUEST and Change-O.

Contact

For help, questions, or suggestions, please contact the Immcantation Group or use the issue tracker.

Dependencies

Depends: ggplot2
Imports: alakazam, tidyr, dplyr, doParallel, foreach, graphics, grid, iterators, lazyeval, parallel, stats
Suggests: knitr, testthat

Authors

Daniel Gadala-Maria (aut)
Jason Vander Heiden (ctb, cre)
Steven Kleinstein (aut, cph)

Citing

Gadala-Maria D, Yaari G, Uduman M and Kleinstein Ss (2015). “Automated analysis of high-throughput B cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles.” Proceedings of the National Academy of Sciency of the United States of America, pp. E862-70.

A BibTeX entry for LaTeX users is

@Article{, title = {Automated analysis of high-throughput B cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles.}, author = {Daniel Gadala-Maria and Gur Yaari and Mohamed Uduman and Steven H. steven.kleinstein@yale.edu Kleinstein}, year = {2015}, journal = {Proceedings of the National Academy of Sciency of the United States of America}, number = {122}, pages = {E862-70}, }