Journal
ALGORITHMS FOR MOLECULAR BIOLOGY
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1748-7188-9-14
Keywords
Alternative topological domains; Chromatin conformation capture; Dynamic programming
Categories
Funding
- National Science Foundation [CCF-1256087, CCF-1053918, EF-0849899]
- National Institutes of Health [R21AI085376, R01HG007104]
- NIH as part of the HHMI-NIBIB Interfaces Initiative [T32 EB009403]
- Division of Computing and Communication Foundations
- Direct For Computer & Info Scie & Enginr [1319998] Funding Source: National Science Foundation
- Division of Computing and Communication Foundations
- Direct For Computer & Info Scie & Enginr [1256087] Funding Source: National Science Foundation
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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.
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