Fig. 1

Overview of COCOA. a A regulatory signal may covary with the epigenetic signal in the genomic regions it regulates. b Covariation of the epigenetic signal in coregulated regions across individuals can be used to infer variation in the regulatory signal. c COCOA can be used with an unsupervised target variable (latent factor), or d with a supervised target variable (phenotype). e The first step is to quantify the relationship between the target variable and the epigenetic data at each locus, resulting in a score for each locus. f The second step is to annotate variation using a database of region sets. Each region set is scored to identify the region sets most associated with covariation between the epigenetic signal and the target variable. These top region sets can yield insight into the biological significance of the epigenetic variation