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Nat Commun. 2019 May 3;10(1):2049. doi: 10.1038/s41467-019-10005-6.

Integrating Hi-C and FISH data for modeling of the 3D organization of chromosomes.

Author information

1
Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China.
2
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
3
School of Life Science, Tsinghua University, Beijing, 100084, China.
4
MOE Key Laboratory of Bioinformatics; Bioinformatics Division, Center for Synthetic and Systems Biology, BNRist; Department of Automation, Tsinghua University; Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China.
5
Department of Biological Sciences, Center for Systems Biology, the University of Texas at Dallas, Richardson, TX, 75080-3021, USA.
6
Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China. zengjy321@tsinghua.edu.cn.
7
MOE Key Laboratory of Bioinformatics; Bioinformatics Division, Center for Synthetic and Systems Biology, BNRist; Department of Automation, Tsinghua University; Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China. zengjy321@tsinghua.edu.cn.

Abstract

The new advances in various experimental techniques that provide complementary information about the spatial conformations of chromosomes have inspired researchers to develop computational methods to fully exploit the merits of individual data sources and combine them to improve the modeling of chromosome structure. Here we propose GEM-FISH, a method for reconstructing the 3D models of chromosomes through systematically integrating both Hi-C and FISH data with the prior biophysical knowledge of a polymer model. Comprehensive tests on a set of chromosomes, for which both Hi-C and FISH data are available, demonstrate that GEM-FISH can outperform previous chromosome structure modeling methods and accurately capture the higher order spatial features of chromosome conformations. Moreover, our reconstructed 3D models of chromosomes revealed interesting patterns of spatial distributions of super-enhancers which can provide useful insights into understanding the functional roles of these super-enhancers in gene regulation.

PMID:
31053705
PMCID:
PMC6499832
DOI:
10.1038/s41467-019-10005-6
[Indexed for MEDLINE]
Free PMC Article

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