GenomeDISCO: A concordance score for chromosome conformation capture experiments using random walks on contact map graphs

Oana Ursu, Nathan Boley, Maryna Taranova, Y. X.Rachel Wang, Galip Gurkan Yardimci, William Stafford Noble, Anshul Kundaje

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Motivation: The three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments such as Hi-C are used to obtain genome-wide maps of three-dimensional chromatin contacts. However, robust estimation of data quality and systematic comparison of these contact maps is challenging due to the multi-scale, hierarchical structure of chromatin contacts and the resulting properties of experimental noise in the data. Measuring concordance of contact maps is important for assessing reproducibility of replicate experiments and for modeling variation between different cellular contexts. Results: We introduce a concordance measure called DIfferences between Smoothed COntact maps (GenomeDISCO) for assessing the similarity of a pair of contact maps obtained from chromosome conformation capture experiments. The key idea is to smooth contact maps using random walks on the contact map graph, before estimating concordance. We use simulated datasets to benchmark GenomeDISCO's sensitivity to different types of noise that affect chromatin contact maps. When applied to a large collection of Hi-C datasets, GenomeDISCO accurately distinguishes biological replicates from samples obtained from different cell types. GenomeDISCO also generalizes to other chromosome conformation capture assays, such as HiChIP.

Original languageEnglish (US)
Pages (from-to)2701-2707
Number of pages7
JournalBioinformatics
Volume34
Issue number16
DOIs
StatePublished - Aug 15 2018
Externally publishedYes

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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