Integrating Hi-C and FISH Data for Modeling of the 3D Organization of Chromosomes




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Nature Publishing Group


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. © 2019, The Author(s).



Chromosomes, Gene expression, Polymers, Three-dimensional modeling, Chromatin, Finite element method, Fluorescence in situ hybridization, Three dimensional imaging, Cell lines, Computer simulation, Genetics, Human genome

This work was supported in part by the National Natural Science Foundation of China (61472205 and 81630103), State Key Research Development Program of China (2017YFA0505503), the National Natural Science Foundation of China under Grant (91729301, 31671383, 61475010, 61729501, and 11671005),


CC BY 4.0 (Attribution), ©2019 The Authors