Abstract

BackgroundIdentification and analysis of recurrent combinatorial patterns of multiple chromatin modifications provide invaluable information for understanding epigenetic regulations. Furthermore, as more data becomes available, it is computationally expensive and unnecessary to study combinatorial patterns of all modifications.MethodsA novel framework is proposed to investigate recurrent combinatorial patterns of a subset of quantitatively selected chromatin modifications. The framework is based on heirarchical clustering and selects subsets of chromatin modifications that form distinct recurrent patterns at regulatory regions. The identified recurrent combinatorial patterns can be further utilized to discover novel regulatory regions. Data is in the form of genome wide maps of histone acetylations, methylations, and histone variant of human skeletal muscular and B-lymphocyte cells both derived from the ENCODE project.ResultsA case study conducted at promoter regions is presented: four out of twelve chromatin modifications were selected, eight different promoter states were identified and the identified patterns of active promoters were further utilized to discover novel promoter regions. Several previously un-annotated promoters were discovered, further investigations confirm their promoter functions.ConclusionsThis framework is approproiately general and could lead to better understanding of epigenetic regulations by discovering previously unknown regulatory regions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1346-5) contains supplementary material, which is available to authorized users.

Highlights

  • Identification and analysis of recurrent combinatorial patterns of multiple chromatin modifications provide invaluable information for understanding epigenetic regulations

  • Affinity matrix of chromatin modifications was generated for each cell line individually

  • The hypothesis is that the distribution of one chromatin modification mark could be expressed as a weighted sum of few related others

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Summary

Introduction

Identification and analysis of recurrent combinatorial patterns of multiple chromatin modifications provide invaluable information for understanding epigenetic regulations. As more data becomes available, it is computationally expensive and unnecessary to study combinatorial patterns of all modifications. Much attention has been spent on investigating recurrent patterns of chromatin modifications [1, 2, 6,7,8,9,10,11,12,13,14,15,16,17]. We propose to analyze a quantitatively selected subset of chromatin modifications. It could simplify the analysis and provide guidance for future experimental design at the same time

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