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Chromatin-state discovery and genome annotation with ChromHMM


Noncoding DNA regions have central roles in human biology, evolution, and disease. ChromHMM helps to annotate the noncoding genome using epigenomic information across one or multiple cell types. It combines multiple genome-wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer a complete annotation for each cell type. ChromHMM learns chromatin-state signatures using a multivariate hidden Markov model (HMM) that explicitly models the combinatorial presence or absence of each mark. ChromHMM uses these signatures to generate a genome-wide annotation for each cell type by calculating the most probable state for each genomic segment. ChromHMM provides an automated enrichment analysis of the resulting annotations to facilitate the functional interpretations of each chromatin state. ChromHMM is distinguished by its modeling emphasis on combinations of marks, its tight integration with downstream functional enrichment analyses, its speed, and its ease of use. Chromatin states are learned, annotations are produced, and enrichments are computed within 1 d.

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Figure 1: Overview of ChromHMM.
Figure 2: Overview of different options for handling multiple cell types in ChromHMM.
Figure 3: Example webpage screenshots.


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We acknowledge the ENCODE and Roadmap Epigenomics consortia for generation and processing of data to which we have previously applied ChromHMM. We acknowledge the users of ChromHMM who have provided useful feedback on the software. We acknowledge funding from U.S. National Institutes of Health grants U54HG004570, RC1HG005334 (M.K.), R01ES024995, U01HG007912 and U01MH105578 (J.E.); a U.S. National Science Foundation Postdoctoral Fellowship (0905968) and CAREER Award 1254200 (J.E.); and an Alfred P. Sloan Fellowship (J.E.).

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J.E. and M.K. wrote this protocol and previously developed ChromHMM.

Corresponding authors

Correspondence to Jason Ernst or Manolis Kellis.

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The authors declare no competing financial interests.

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Ernst, J., Kellis, M. Chromatin-state discovery and genome annotation with ChromHMM. Nat Protoc 12, 2478–2492 (2017).

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