Article

Ernst J, Kellis M.ChromHMM: automating chromatin-state discovery and characterization. Nat Methods 9:215-216

1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA. [3] Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California, USA.
Nature Methods (Impact Factor: 32.07). 02/2012; 9(3):215-6. DOI: 10.1038/nmeth.1906
Source: PubMed

ABSTRACT

To the Editor:
Chromatin-state annotation using combinations of chromatin modification patterns has emerged as a powerful approach for discovering regulatory regions and their cell type–specific activity patterns and for interpreting disease-association studies1, 2, 3, 4, 5. However, the computational challenge of learning chromatin-state models from large numbers of chromatin modification datasets in multiple cell types still requires extensive bioinformatics expertise. To address this challenge, we developed ChromHMM, an automated computational system for learning chromatin states, characterizing their biological functions and correlations with large-scale functional datasets and visualizing the resulting genome-wide maps of chromatin-state annotations.

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    • "The input information used to segment the genome into different chromatin states was that derived from the three cytosine modifications, the 13 histone marks, and the insulator protein CTCF—which has been previously shown to define a particular chromatin state per se (Ernst and Kellis, 2010). We used the ChromHmm software (Ernst and Kellis, 2012; v1.03) to define a 20-chromatin- states model consistent with prior knowledge regarding the function of these features (Figure S3). Only intervals with a probability higher than 0.95 were considered for further analysis. "
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    • "The two CpGs highlighted are located in intron 1 which is an active regulatory region according to ENCODE[27]. This region is a 4 kb promoter-associated region surrounding the transcription start site (TSS) of CPT1A in the HepG2 cell line ( " Active TSS " according to chromHMM)[28]. There are several transcription factor binding sites near our highlighted CpGs. "
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    • "mouse limb (Visel et al. 2007); and TSAR.1586, expression in e14.5 brain (Shen et al. 2012). Using ENCODE data, chromHMM (Ernst and Kellis 2012) predicted that eight others are also enhancers. While both Lhx1 and Mrm1 are widely expressed, the LIM-homeodomain transcription factors are important for mammalspecific forebrain development and many of them are expressed together in specific subregions (Abellan et al. 2010). "
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