Toward breaking the histone code: bayesian graphical models for histone modifications

Circ Cardiovasc Genet. 2013 Aug;6(4):419-26. doi: 10.1161/CIRCGENETICS.113.000100. Epub 2013 Jun 7.

Abstract

Background: Histones are proteins that wrap DNA around in small spherical structures called nucleosomes. Histone modifications (HMs) refer to the post-translational modifications to the histone tails. At a particular genomic locus, each of these HMs can either be present or absent, and the combinatory patterns of the presence or absence of multiple HMs, or the histone codes, are believed to coregulate important biological processes. We aim to use raw data on HM markers at different genomic loci to (1) decode the complex biological network of HMs in a single region, and (2) demonstrate how the HM networks differ in different regulatory regions. We suggest that these differences in network attributes form a significant link between histones and genomic functions.

Methods and results: We develop a powerful graphical model under the Bayesian paradigm. Posterior inference is fully probabilistic, allowing us to compute the probabilities of distinct dependence patterns of the HMs using graphs. Furthermore, our model-based framework allows for easy but important extensions for inference on differential networks under various conditions, such as the different annotations of the genomic locations (eg, promoters versus insulators). We applied these models to ChIP-Seq data based on CD4+ T lymphocytes. The results confirmed many existing findings and provided a unified tool to generate various promising hypotheses. Differential network analyses revealed new insights on coregulation of HMs of transcriptional activities in different genomic regions.

Conclusions: The use of Bayesian graphical models and borrowing strength across different conditions provide high power to infer histone networks and their differences.

Keywords: epigenomics; gene expression regulation; graph; models, statistical; network; nucleosomes; statistics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bayes Theorem
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Chromatin Immunoprecipitation
  • Epigenomics
  • Histone Code*
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Models, Statistical*
  • Sequence Analysis, DNA

Substances

  • Histones