A framework for summarizing chromatin state annotations within and identifying differential annotations across groups of samples

Abstract

MotivationGenome-wide maps of epigenetic modifications are powerful resources for non-coding genome annotation. Maps of multiple epigenetics marks have been integrated into cell or tissue type-specific chromatin state annotations for many cell or tissue types. With the increasing availability of multiple chromatin state maps for biologically similar samples, there is a need for methods that can effectively summarize the information about chromatin state annotations within groups of samples and identify differences across groups of samples at a high resolution. ResultsWe developed CSREP, which takes as input chromatin state annotations for a group of samples and then probabilistically estimates the state at each genomic position and derives a representative chromatin state map for the group. CSREP uses an ensemble of multi-class logistic regression classifiers to predict the chromatin state assignment of each sample given the state maps from all other samples. The difference of CSREPs probability assignments for two groups can be used to identify genomic locations with differential chromatin state patterns. Using groups of chromatin state maps of a diverse set of cell and tissue types, we demonstrate the advantages of using CSREP to summarize chromatin state maps and identify biologically relevant differences between groups at a high resolution. Availability and implementationThe CSREP source code is openly available under http://github.com/ernstlab/csrep. Contact: jason.ernst@ucla.edu