HiHMM: Bayesian non-parametric joint inference of chromatin state maps

Abstract

Motivation: Genome-wide mapping of chromatin states is essential for defining regulatory elements and inferring their activities in eukaryotic genomes. A number of hidden Markov model (HMM)-based methods have been developed to infer chromatin state maps from genome-wide histone modification data for an individual genome. To perform a principled comparison of evolutionarily distant epigenomes, we must consider species-specific biases such as differences in genome size, strength of signal enrichment and co-occurrence patterns of histone modifications. Results: Here, we present a new Bayesian non-parametric method called hierarchically linked infinite HMM (hiHMM) to jointly infer chromatin state maps in multiple genomes (different species, cell types and developmental stages) using genome-wide histone modification data. This flexible framework provides a new way to learn a consistent definition of chromatin states across multiple genomes, thus facilitating a direct comparison among them. We demonstrate the utility of this method using synthetic data as well as multiple modENCODE ChIP-seq datasets. Conclusion: The hierarchical and Bayesian non-parametric formulation in our approach is an important extension to the current set of methodologies for comparative chromatin landscape analysis. Availability and implementation: Source codes are available at https://github.com/kasohn/hiHMM. Chromatin data are available at http://encode-x.med.harvard.edu/data-sets/chromatin/.