A maximum-entropy model for predicting chromatin contacts

PLoS Comput Biol. 2018 Feb 5;14(2):e1005956. doi: 10.1371/journal.pcbi.1005956. eCollection 2018 Feb.

Abstract

The packaging of DNA inside a nucleus shows complex structure stabilized by a host of DNA-bound factors. Both the distribution of these factors and the contacts between different genomic locations of the DNA can now be measured on a genome-wide scale. This has advanced the development of models aimed at predicting the conformation of DNA given only the locations of bound factors-the chromatin folding problem. Here we present a maximum-entropy model that is able to predict a contact map representation of structure given a sequence of bound factors. Non-local effects due to the sequence neighborhood around contacting sites are found to be important for making accurate predictions. Lastly, we show that the model can be used to infer a sequence of bound factors given only a measurement of structure. This opens up the possibility for efficiently predicting sequence regions that may play a role in generating cell-type specific structural differences.

MeSH terms

  • Algorithms
  • Animals
  • Bayes Theorem
  • Chromatin / chemistry*
  • Cluster Analysis
  • DNA / chemistry*
  • Drosophila melanogaster / physiology*
  • Gene Expression Profiling
  • Genome
  • Models, Statistical
  • Mutation
  • Nucleic Acid Conformation
  • Polymers / chemistry
  • Probability
  • Protein Binding
  • Protein Folding
  • Proteins / chemistry

Substances

  • Chromatin
  • Polymers
  • Proteins
  • DNA

Grants and funding

The authors received no specific funding for this work.