EpiMix is an integrative tool for epigenomic subtyping using DNA methylation

DNA methylation (DNAme) is a major epigenetic factor influencing gene expression with alterations leading to cancer and immunological and cardiovascular diseases. Recent technological advances have enabled genome-wide profiling of DNAme in large human cohorts. There is a need for analytical methods that can more sensitively detect differential methylation profiles present in subsets of individuals from these heterogeneous, population-level datasets. We developed an end-to-end analytical framework named “EpiMix” for population-level analysis of DNAme and gene expression. Compared with existing methods, EpiMix showed higher sensitivity in detecting abnormal DNAme that was present in only small patient subsets. We extended the model-based analyses of EpiMix to cis-regulatory elements within protein-coding genes, distal enhancers, and genes encoding microRNAs and long non-coding RNAs (lncRNAs). Using cell-type-specific data from two separate studies, we discover epigenetic mechanisms underlying childhood food allergy and survival-associated, methylation-driven ncRNAs in non-small cell lung cancer.