Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

PLoS Comput Biol. 2015 May 12;11(5):e1004221. doi: 10.1371/journal.pcbi.1004221. eCollection 2015 May.

Abstract

The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology*
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Chromatin / ultrastructure
  • Chromosomes
  • Gene Expression Regulation*
  • Genome
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Genetic
  • Structure-Activity Relationship

Substances

  • Chromatin

Grants and funding

This research has received partial funding from the Dutch Technology Foundation STW, as part of the STW project 12721 (“Genes in Space”) under the IMAGENE Perspective program, and from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 604102 (Human Brain Project). JdR is supported by the Netherlands Organisation for Scientific Research (NWO-Veni: 639.021.233). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.