HTRX: an R package for learning non-contiguous haplotypes associated with a phenotype

SUMMARY: Haplotype Trend Regression with eXtra flexibility (HTRX) is an R package to learn sets of interacting features that explain variance in a phenotype. Genome-wide association studies (GWAS) have identified thousands of single nucleotide polymorphisms (SNPs) associated with complex traits and diseases, but finding the true causal signal from a high linkage disequilibrium block is challenging. We focus on the simpler task of quantifying the total variance explainable not just with main effects but also interactions and tagging, using haplotype-based associations. HTRX identifies haplotypes composed of non-contiguous SNPs associated with a phenotype and can naturally be performed on regions with a GWAS hit before or after fine-mapping. To reduce the space and computational complexity when investigating many features, we constrain the search by growing good feature sets using ‘Cumulative HTRX’, and limit the maximum complexity of a feature set. As the computational time scales linearly with the number of SNPs, HTRX has the potential to be applied to large chromosome regions. AVAILABILITY AND IMPLEMENTATION: HTRX is implemented in R and is available under GPL-3 licence from CRAN (https://cran.r-project.org/web/packages/HTRX/readme/README.html). The development version is maintained on GitHub (https://github.com/YaolingYang/HTRX). CONTACT: yaoling.yang@bristol.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics Advances online.