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Algorithms Mol Biol. 2014 May 3;9:14. doi: 10.1186/1748-7188-9-14. eCollection 2014.

Identification of alternative topological domains in chromatin.

Author information

1
Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh PA, USA.
2
Joint Carnegie Mellon University - University of Pittsburgh Ph.D. Program in Computational Biology, Pittsburgh PA, USA.
#
Contributed equally

Abstract

Chromosome conformation capture experiments have led to the discovery of dense, contiguous, megabase-sized topological domains that are similar across cell types and conserved across species. These domains are strongly correlated with a number of chromatin markers and have since been included in a number of analyses. However, functionally-relevant domains may exist at multiple length scales. We introduce a new and efficient algorithm that is able to capture persistent domains across various resolutions by adjusting a single scale parameter. The ensemble of domains we identify allows us to quantify the degree to which the domain structure is hierarchical as opposed to overlapping, and our analysis reveals a pronounced hierarchical structure in which larger stable domains tend to completely contain smaller domains. The identified novel domains are substantially different from domains reported previously and are highly enriched for insulating factor CTCF binding and histone marks at the boundaries.

KEYWORDS:

Alternative topological domains; Chromatin conformation capture; Dynamic programming

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