Introduction - tigger (original) (raw)

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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.

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

Dependencies¶

Depends: ggplot2
Imports: alakazam, dplyr, doParallel, foreach, graphics, gridExtra, gtools, iterators, lazyeval, parallel, rlang, stats, stringi, tidyr, utils
Suggests: knitr, rmarkdown, testthat

Daniel Gadala-Maria (aut)
Susanna Marquez (aut, cre)
Moriah Cohen (aut)
Jason Vander Heiden (aut)
Gur Yaari (aut)
Steven Kleinstein (aut, cph)

Citing¶

Gadala-Maria D, Yaari G, Uduman M, Kleinstein S (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, E862-70. doi:10.1073/pnas.1417683112https://doi.org/10.1073/pnas.1417683112.

Gadala-Maria D, Gidoni M, Marquez S, Vander Heiden J, Kos J, Watson C, O’connor K, Yaari G, Kleinstein S (2019). “Identification of Subject-Specific Immunoglobulin Alleles From Expressed Repertoire Sequencing Data.” Frontiers in Immunology, 129. doi:10.3389/fimmu.2019.00129https://doi.org/10.3389/fimmu.2019.00129.

License¶

AGPL-3