Case-Control Analysis of Multi-Allelic Loci

Data sets and functions for chi-squared Hardy-Weinberg and case-control association tests of highly polymorphic genetic data [e.g., human leukocyte antigen (HLA) data]. Performs association tests at multiple levels of polymorphism (haplotype, locus and HLA amino-acids) as described in Pappas DJ, Marin W, Hollenbach JA, Mack SJ (2016) . Combines rare variants to a common class to account for sparse cells in tables as described by Hollenbach JA, Mack SJ, Thomson G, Gourraud PA (2012) .


BIGDAWG v1.16 (Release date: 2017-09-05) Derek Pappas [email protected]

  • Some code re-structuring.
  • Added parameter check function.
  • Updated bundled IMGT/HLA amino acid exon alignment to latest release (Release, 2017-08-18).

BIGDAWG v1.15.3 (Release date: 2017-08-07) Derek Pappas [email protected]

  • Now Data argument accepts properly formatted R dataframes (Data=foo).

BIGDAWG v1.15.2 (Release date: 2017-08-07) Derek Pappas [email protected]

  • Release v1.15.1 restricted to internal releases.
  • Fixed miscellaneous bugs specific to HLA data processing.
  • Now allows for .1, .2, _1, and _2 in column names.
  • Updates to vignette.

BIGDAWG v1.15 (Release date: 2017-08-02) Derek Pappas [email protected]

  • Fixed miscellaneous bugs specific to HLA data processing.
  • Minor adjustments to code for organization and clarity.

BIGDAWG v1.14.2 (Release date: 2017-07-18) Derek Pappas [email protected]

  • Fixed bug where allele names with '00' would be eroneously changed.

BIGDAWG v1.14.1 (Release date: 2017-07-10) Derek Pappas [email protected]

  • Minor adjustments to code for organization and clarity.
  • Fixed bug where sample IDs were not exporting with subject haplotypes. However, they were reported in the same order as the source data.

BIGDAWG v1.14 (Release date: 2017-07-09) Derek Pappas [email protected]

  • Adjusted maximum multi-core allowance to 90% of available processor cores.

BIGDAWG v1.13 (Release date: 2017-07-07) Derek Pappas [email protected]


  • Submission to CRAN
  • Minor vignette updates.

BIGDAWG v1.12 (Release date: 2017-06-21) Derek Pappas [email protected]


  • BIGDAWG v1.10 and v1.11 restricted to internal releases.
  • Transferred github repository location to
  • Added multi-core capabilities to haplotype analysis to speed up pairwise analysis. Useful for large datasets.
  • Update to haplotype output files.
  • Analysis results can be merged into single files with Merge.Output=T. Not recommend for very large datasets and running all pairwise combinations in the haplotype analysis.
  • Updated bundled IMGT/HLA amino acid exon alignment to latest release (Release 3.28.0, 2017-04-13)

BIGDAWG v1.9 (Release date: 2017-01-20) Derek Pappas [email protected]


  • Added warning that when All.Pairwise=T or the locus or amino acid tests are run with multiple sets, there will be duplication of analyses and results when sets contain overlapping loci.
  • When All.Pairwise=T, only pairwise combinations are run in the haplotype analysis.
  • Changes to output list structure when Return=T.
  • Updated bundled IMGT/HLA amino acid exon alignment to latest release (Release 3.27.0, 2017-01-20)

BIGDAWG v1.8.4 (Release date: 2017-01-12) Derek Pappas [email protected]


  • Naming update to haplotype output files. Haplotype loci will no longer be appended to the filename. When All.Pairwise=T, the filename will be appended with "PairwiseSet" and the set number. A file will also be written to indicate which pairwise set corresponds to which haplotypes.

BIGDAWG v1.8.3 (Release date: 2016-12-26) Derek Pappas [email protected]


  • Updated vignette

BIGDAWG v1.8.2 (Release date: 2016-12-14) Derek Pappas [email protected]


  • Small adjustments to console output for clarity and grammar.
  • Moved knitr and rmarkdown from Suggests to Imports.

BIGDAWG v1.8.1 (Release date: 2016-12-13) Derek Pappas [email protected]


  • Adjustment to data output merging function.
  • Small fix to 'A' analysis when output to object.

BIGDAWG v1.8 (Release date: 2016-12-10) Derek Pappas [email protected]


  • Added output of merged analyses to main output folder (only when Output = T).

BIGDAWG v1.7 (Release date: 2016-12-08) Derek Pappas [email protected]


  • Adjusted function for counting missing alleles to avoid memory limitations. Ported from haplo.stats.

BIGDAWG v1.6 (Release date: 2016-12-02) Derek Pappas [email protected]


  • Update bundled IMGT/HLA amino acid exon alignment to latest release (
  • Update to URL for downloading *_prot.txt alignment files
  • Small fixes to UpdateRelease code when downloading alignment files from IMGT.

BIGDAWG v1.5.8 (Release date: 2016-12-02) Derek Pappas [email protected]


  • Fix bug that may be encountered when specifying a set of loci to run.

BIGDAWG v1.5.7 (Release date: 2016-10-05) Derek Pappas [email protected]


  • Pandoc requirement for installing from GitHub without RStudio. Thanks to Hugh Salamon.

BIGDAWG v1.5.6 (Release date: 2016-09-14) Derek Pappas [email protected]


  • URL change for 'hla_nom_p.txt' download. Thanks to Hugh Salamon.

BIGDAWG v1.5.5 (Release date: 2016-08-29) Derek Pappas [email protected]


  • Bug fixed - accidently introduced in v1.5.4 that would cause 'A' test failure

BIGDAWG v1.5.4 (Release date: 2016-08-26) Derek Pappas [email protected]


  • Small changes in code organization.
  • Update bundled IMGT/HLA amino acid exon alignment to latest release (3.25.0)

BIGDAWG v1.5.3 (Release date: 2016-08-25) Derek Pappas [email protected]


  • Fix bug in UpdateRelease() on some installations.

BIGDAWG v1.5.2 (Release date: 2016-08-03) Derek Pappas [email protected]


  • Fix for an incorrect error message wording. Thanks to Farrel Buchinsky.
  • Fix for data read-in when 1-Field resolution. Thanks to Farrel Buchinsky.

BIGDAWG v1.5.1 (Release date: 2016-06-20) Derek Pappas [email protected]


  • Bug fix in output list.

BIGDAWG v1.5.0 (Release date: 2016-06-15) Derek Pappas [email protected]


  • BIGDAWG can now return results as list with parameter Return=T.
  • Minimize console output with Verbose=F.
  • Turn off write results to file with Output=F.
  • Bug fix for DRB3/4/5 parsing with NA's.

BIGDAWG v1.4.0 (Release date: 2016-05-12) Derek Pappas [email protected]


  • Version change, submission to CRAN.

BIGDAWG v1.3.9 (Release date: 2016-05-11) Derek Pappas [email protected]


  • Vignette link modifications.
  • Bug fix for UpdateRelease() when there is no internet connection.

BIGDAWG v1.3.8 (Release date: 2016-05-04) Derek Pappas [email protected]


  • Error message for allele formatting imbalance across loci when HLA=T.

BIGDAWG v1.3.7 (Release date: 2016-04-29) Derek Pappas [email protected]


  • Bug fix for CheckRelease() when there is no internet connection.
  • Bug fix when setting Output=F, for testing only.
  • Bug fix HWE displaying control analysis twice.
  • Minor changes to vignette.
  • Adjust Errors to only print out when Output=T.

BIGDAWG v1.3.6 (Release date: 2016-04-26) Derek Pappas [email protected]


  • Added function to check BIGDAWG version and IMGT/HLA version simultaneously using CheckRelease().
  • Removed UpdateRelease(GetRelease). See vignette.
  • Vignette update to reflect changes.

BIGDAWG v1.3.5 (Release date: 2016-04-20) Derek Pappas [email protected]


  • Minor wording change to vignette to enhance clarity and reflect GitHub availability.
  • Added function to check release BIGDAWG uses for IMGT/HLA database. See vignette.
  • Added Hardy Weinberg Equilibrium testing for cases. Useful when employing other binary phenotypes.
  • Update bundled IMGT/HLA amino acid exon alignment to latest release (3.24.0)

BIGDAWG v1.3.4 (Release date: 2016-04-08) Derek Pappas [email protected]


  • Added output of subject haplotypes to file when running haplotype analysis.
  • Bug fix in haplotype generation and outputs.
  • Bug fix in when locus has only a single allele. Thanks go to Antoine Lizee.
  • Other minor improvements to enhance data processing.
  • Minor wording change to vignette to enhance clarity.
  • Updated Human Immunology paper to BIGDAWG.

BIGDAWG v1.3.1 - v1.3.3 (Internal Releases) Derek Pappas [email protected]


  • Added ability to read in HLA data when DRB3, DRB4, and DRB5 are collapsed to a single column. DR haplotypes are parsed accordingly. See vignette for details.
  • Added output of Sample IDs removed due to missing alleles exceeding set threshold.
  • Adjusted Missing default to 2.
  • When running multiple locus sets the for haplotype analysis, now displays which haplotype is being run.

BIGDAWG v1.2.8 (Release date: 2016-02-28) Derek Pappas [email protected]


  • Bug fix.

BIGDAWG v1.2.7 (Release date: 2016-02-27) Derek Pappas [email protected]


  • Bug fix for chi square output using some data sets.

BIGDAWG v1.2.6 (Release date: 2016-02-19) Derek Pappas [email protected]


  • BIDAWG v1.2.1 - v1.2.5 unreleased internal versions.
  • Bug fix when removing missing data as set by 'Missing' parameter. Thanks go to Arun Khattri.
  • Added reference to BIGDAWG publication in DESCRIPTION and vignette.
  • Update bundled IMGT/HLA amino acid exon alignment to latest release (3.23.0)

BIGDAWG v1.2.1 (Release date: 2015-11-09) Derek Pappas [email protected]


  • Added NEWS file to document BIGDAWG releases.
  • Bug fix when EVS.rm was set to TRUE.
  • Precheck.txt renamed to Data_Summary.txt.
  • Distinction between Run parameters and Set parameters.
  • Run Parameters generated and written to file earlier in script.
  • Added section delimiter for 'Data Processing And Checks' in console output.
  • Changes in wording for select BIGDAWG error messages.
  • Update to Hardy-Weinberg test.
  • Update bundled IMGT/HLA amino acid exon alignment to latest release (3.22.0)

Reference manual

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2.1 by Steve Mack, 4 months ago,

Report a bug at

Browse source code at

Authors: Derek Pappas <[email protected]>, Steve Mack <[email protected]>, Jill Hollenbach <[email protected]>

Documentation:   PDF Manual  

GPL (>= 3) license

Imports XML, httr, haplo.stats, parallel, knitr, rmarkdown

See at CRAN