To identify patterns of coordinated changes of histone marks over enhancers during heart muscle development, we compared ESCs, Mesendoderm cells, and Left Ventricle tissue56. We identified relevant enhancers as those that show changes in at least one histone mark between a specific cell type cluster (heart muscle in our case) and other cell types using LIMMA (Linear Model for Microarray Analysis). We applied FDR corrected P-value significance threshold of 0.05 to obtain cluster-specific enhancers. For each tissue type (heart muscle in our case) we then clustered the enhancers into five clusters (C1-C5) based on their multi-mark epigenomic profiles using the k-means algorithm implemented in the Spark tool (Fig. 4i). The tools used to generate Fig. 4i are integrated into the Epigenomic Toolset within the Genboree Workbench and are accessible for online use at www.genboree.org.
