SHazaM

SHazaM is part of the Immcantation analysis framework for Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) and provides tools for advanced analysis of somatic hypermutation (SHM) in immunoglobulin (Ig) sequences. Shazam focuses on the following
analysis topics:

  1. Quantification of mutational load
    SHazaM includes methods for determine the rate of observed and expected mutations under various criteria. Mutational profiling criteria include rates under SHM targeting models, mutations specific to CDR and FWR regions, and physicochemical property dependent substitution rates.
  2. Statistical models of SHM targeting patterns
    Models of SHM may be divided into two independent components: (a) a mutability model that defines where mutations occur and (b) a nucleotide substitution model that defines the resulting mutation. Collectively these two components define an SHM targeting model. SHazaM provides empirically derived SHM 5-mer context mutation models for both humans and mice, as well tools to build SHM targeting models from data.
  3. Analysis of selection pressure using BASELINe
    The Bayesian Estimation of Antigen-driven Selection in Ig Sequences (BASELINe) method is a novel method for quantifying antigen-driven selection in high-throughput Ig sequence data. BASELINe uses SHM targeting models can be used to estimate the null distribution of expected mutation frequencies, and provide measures of selection pressure informed by known AID targeting biases.
  4. Model-dependent distance calculations
    SHazaM provides methods to compute evolutionary distances between sequences or set of sequences based on SHM targeting models. This information is particularly useful in understanding and defining clonal relationships.

Contact

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

Dependencies

Depends: ggplot2
Imports: alakazam, ape, diptest, doParallel, dplyr, foreach, graphics, grid, igraph, iterators, KernSmooth, lazyeval, MASS, methods, parallel, progress, rlang, scales, seqinr, stats, stringi, tidyr, tidyselect, utils
Suggests: knitr, rmarkdown, testthat

Authors

Mohamed Uduman (aut)
Namita Gupta (aut)
Susanna Marquez (aut, cre)
Julian Zhou (aut)
Nima Nouri (aut)
Noah Yann Lee (aut)
Ang Cui (ctb)
Jason Vander Heiden (aut)
Gur Yaari (aut)
Steven Kleinstein (aut, cph)

Citing

To cite the SHazaM package in publications, please use:

Gupta N, Vander Heiden J, Uduman M, Gadala-Maria D, Yaari G, Kleinstein S (2015). “Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data.” Bioinformatics, 1-3. doi:10.1093/bioinformatics/btv359 https://doi.org/10.1093/bioinformatics/btv359.

To cite the selection analysis methods, please use:

Yaari G, Uduman M, Kleinstein S (2012). “Quantifying selection in high-throughput Immunoglobulin sequencing data sets.” Nucleic acids research, 40(17), e134. doi:10.1093/nar/gks457 https://doi.org/10.1093/nar/gks457.

To cite the HH_S5F model and the targeting model generation methods, please use:

Yaari G, Vander Heiden J, Uduman M, Gadala-Maria D, Gupta N, Stern J, O’Connor K, Hafler D, Lasserson U, Vigneault F, Kleinstein S (2013). “Models of somatic hypermutation targeting and substitution based on synonymous mutations from high-throughput immunoglobulin sequencing data.” Frontiers in Immunology, 4(358), 1-11. doi:10.3389/fimmu.2013.00358 https://doi.org/10.3389/fimmu.2013.00358.

To cite the HKL_S1F, HKL_S5F, MK_RS1NF, and MK_RS5NF models, please use:

Cui A, Di Niro R, Vander Heiden J, Briggs A, Adams K, Gilbert T, O’Connor K, Vigneault F, Shlomchik M, Kleinstein S (2016). “A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data.” The Journal of Immunology, 197(9), 3566-3574. doi:10.4049/jimmunol.1502263 https://doi.org/10.4049/jimmunol.1502263.

License

AGPL-3