Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline

Abstract

Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci. BIGDAWG performs tests for Hardy-Weinberg equilibrium, calculates allele frequencies and bins low-frequency alleles for k×2 and 2×2 chi-squared tests, and calculates odds ratios, confidence intervals and p-values for each allele. When multi-locus genotype data are available, BIGDAWG estimates user-specified haplotypes and performs the same binning and statistical calculations for each haplotype. For the HLA loci, BIGDAWG performs the same analyses at the individual amino-acid level. Finally, BIGDAWG generates figures and tables for each of these comparisons. BIGDAWG obviates the error-prone reformatting needed to traffic data between multiple programs, and streamlines and standardizes the data-analysis process for case-control studies of highly polymorphic data. BIGDAWG has been implemented as the bigdawg R package and as a free web application at bigdawg.immunogenomics.org.

Keywords: Amino-acid analysis; BIGDAWG; Case-control analysis; HLA KIR data analysis; Haplotype analysis; Hardy–Weinberg testing; R package; Web app.

Figure 1. Summary Statistics and Hardy-Weinberg Equilibrium Analysis

Sig (significance) column. * indicates a significant p-value. These p-values have not been corrected for multiple comparisons.

Figure 2. Summarized Association Testing Results

Sig (significance) column. * indicates a significant p-value. These p-values have not been corrected for multiple comparisons. The Amino Acid Analysis results have been shorted for publication.