A unified framework for inferring the multi-scale organization of chromatin domains from Hi-C.

Autor: Bak JH; Korea Institute for Advanced Study, Seoul, Korea., Kim MH; Korea Institute for Advanced Study, Seoul, Korea., Liu L; Korea Institute for Advanced Study, Seoul, Korea.; Department of Physics, Zhejiang Sci-Tech University, Hangzhou, China., Hyeon C; Korea Institute for Advanced Study, Seoul, Korea.; Center for Artificial Intelligence and Natural Sciences, Korea Institute for Advanced Study, Seoul, Korea.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2021 Mar 16; Vol. 17 (3), pp. e1008834. Date of Electronic Publication: 2021 Mar 16 (Print Publication: 2021).
DOI: 10.1371/journal.pcbi.1008834
Abstrakt: Chromosomes are giant chain molecules organized into an ensemble of three-dimensional structures characterized with its genomic state and the corresponding biological functions. Despite the strong cell-to-cell heterogeneity, the cell-type specific pattern demonstrated in high-throughput chromosome conformation capture (Hi-C) data hints at a valuable link between structure and function, which makes inference of chromatin domains (CDs) from the pattern of Hi-C a central problem in genome research. Here we present a unified method for analyzing Hi-C data to determine spatial organization of CDs over multiple genomic scales. By applying statistical physics-based clustering analysis to a polymer physics model of the chromosome, our method identifies the CDs that best represent the global pattern of correlation manifested in Hi-C. The multi-scale intra-chromosomal structures compared across different cell types uncover the principles underlying the multi-scale organization of chromatin chain: (i) Sub-TADs, TADs, and meta-TADs constitute a robust hierarchical structure. (ii) The assemblies of compartments and TAD-based domains are governed by different organizational principles. (iii) Sub-TADs are the common building blocks of chromosome architecture. Our physically principled interpretation and analysis of Hi-C not only offer an accurate and quantitative view of multi-scale chromatin organization but also help decipher its connections with genome function.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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