Combinatorial epigenetic patterns as quantitative predictors of chromatin biology

BMC Genomics
Marcin Cieślik, Stefan Bekiranov

Abstract

Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) is the most widely used method for characterizing the epigenetic states of chromatin on a genomic scale. With the recent availability of large genome-wide data sets, often comprising several epigenetic marks, novel approaches are required to explore functionally relevant interactions between histone modifications. Computational discovery of "chromatin states" defined by such combinatorial interactions enabled descriptive annotations of genomes, but more quantitative approaches are needed to progress towards predictive models. We propose non-negative matrix factorization (NMF) as a new unsupervised method to discover combinatorial patterns of epigenetic marks that frequently co-occur in subsets of genomic regions. We show that this small set of combinatorial "codes" can be effectively displayed and interpreted. NMF codes enable dimensionality reduction and have desirable statistical properties for regression and classification tasks. We demonstrate the utility of codes in the quantitative prediction of Pol2-binding and the discrimination between Pol2-bound promoters and enhancers. Finally, we show that specific codes can be linked to molecular pathways and targ...Continue Reading

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Citations

Dec 1, 2015·BioData Mining·Marcin Cieślik, Stefan Bekiranov
Mar 27, 2015·Bioinformatics·Michiaki HamadaKiyoshi Asai
May 19, 2017·Epigenetics & Chromatin·Francesco Gandolfi, Anna Tramontano
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Sep 5, 2018·BMC Bioinformatics·Hani Z GirgisZachary E Reyes

Related Concepts

Chromatin
Histone H7
Early Promoters, Genetic
Plasma Protein Binding Capacity
Receiver Operating Characteristic
Virtual Systems
Area Under Curve
Twitter Messaging
Principal Component Analysis
Chromatin Immunoprecipitation

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