Identification of hierarchical chromatin domains
#MMPMID26315910
Weinreb C
; Raphael BJ
Bioinformatics
2016[Jun]; 32
(11
): 1601-9
PMID26315910
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MOTIVATION: The three-dimensional structure of the genome is an important
regulator of many cellular processes including differentiation and gene
regulation. Recently, technologies such as Hi-C that combine proximity ligation
with high-throughput sequencing have revealed domains of self-interacting
chromatin, called topologically associating domains (TADs), in many organisms.
Current methods for identifying TADs using Hi-C data assume that TADs are
non-overlapping, despite evidence for a nested structure in which TADs and
sub-TADs form a complex hierarchy. RESULTS: We introduce a model for
decomposition of contact frequencies into a hierarchy of nested TADs. This model
is based on empirical distributions of contact frequencies within TADs, where
positions that are far apart have a greater enrichment of contacts than positions
that are close together. We find that the increase in contact enrichment with
distance is stronger for the inner TAD than for the outer TAD in a TAD/sub-TAD
pair. Using this model, we develop the TADtree algorithm for detecting
hierarchies of nested TADs. TADtree compares favorably with previous methods,
finding TADs with a greater enrichment of chromatin marks such as CTCF at their
boundaries. AVAILABILITY AND IMPLEMENTATION: A python implementation of TADtree
is available at http://compbio.cs.brown.edu/software/ CONTACT:
braphael@cs.brown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available
at Bioinformatics online.
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