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HiTAD: detecting the structural and functional hierarchies of topologically associating domains from chromatin interactions
- Source :
- Nucleic Acids Research
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- A current question in the high-order organization of chromatin is whether topologically associating domains (TADs) are distinct from other hierarchical chromatin domains. However, due to the unclear TAD definition in tradition, the structural and functional uniqueness of TAD is not well studied. In this work, we refined TAD definition by further constraining TADs to the optimal separation on global intra-chromosomal interactions. Inspired by this constraint, we developed a novel method, called HiTAD, to detect hierarchical TADs from Hi-C chromatin interactions. HiTAD performs well in domain sensitivity, replicate reproducibility and inter cell-type conservation. With a novel domain-based alignment proposed by us, we defined several types of hierarchical TAD changes which were not systematically studied previously, and subsequently used them to reveal that TADs and sub-TADs differed statistically in correlating chromosomal compartment, replication timing and gene transcription. Finally, our work also has the implication that the refinement of TAD definition could be achieved by only utilizing chromatin interactions, at least in part. HiTAD is freely available online.
- Subjects :
- 0301 basic medicine
Computational biology
Biology
Cell Line
Domain (software engineering)
03 medical and health sciences
0302 clinical medicine
Dna genetics
Genetics
Animals
Humans
Compartment (development)
Replication timing
Genome
Computational Biology
Reproducibility of Results
DNA
Chromatin Assembly and Disassembly
Chromatin
DNA metabolism
030104 developmental biology
Methods Online
K562 Cells
Algorithms
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....27bffedda4176ea930a7bfb6c8c327c0