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

被引:50
作者
Abbas, Ahmed [1 ]
He, Xuan [1 ]
Niu, Jing [2 ]
Zhou, Bin [3 ]
Zhu, Guangxiang [1 ]
Ma, Tszshan [2 ]
Song, Jiangpeikun [3 ]
Gao, Juntao [4 ,5 ,6 ,7 ]
Zhang, Michael Q. [2 ,4 ,5 ,6 ,7 ,8 ]
Zeng, Jianyang [1 ,4 ,5 ,6 ,7 ]
机构
[1] Tsinghua Univ, Inst Interdisciplinary Informat Sci, Beijing 100084, Peoples R China
[2] Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China
[3] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
[4] Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China
[5] Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, BNRist, Beijing 100084, Peoples R China
[6] Tsinghua Univ, Dept Automat, Beijing 100084, Peoples R China
[7] Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China
[8] Univ Texas Dallas, Ctr Syst Biol, Dept Biol Sci, Richardson, TX 75080 USA
基金
中国国家自然科学基金;
关键词
SPATIAL-ORGANIZATION; GENOME; REVEALS; PRINCIPLES; TRANSCRIPTION; CONFORMATION; PREDICTION; DOMAINS;
D O I
10.1038/s41467-019-10005-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:14
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