整合 Hi-C 和 FISH 数据以构建染色体的 3D 结构模型。
Integrating Hi-C and FISH data for modeling of the 3D organization of chromosomes.
机构信息
Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
出版信息
Nat Commun. 2019 May 3;10(1):2049. doi: 10.1038/s41467-019-10005-6.
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.
各种提供有关染色体空间构象的互补信息的实验技术的新进展激发了研究人员开发计算方法，以充分利用各个数据源的优点并将它们结合起来，从而改进染色体结构的建模。在这里，我们提出了 GEM-FISH 方法，该方法通过系统地将 Hi-C 和 FISH 数据与聚合物模型的先验生物物理知识相结合，来重建染色体的 3D 模型。在一组染色体上进行的综合测试，这些染色体均具有 Hi-C 和 FISH 数据，表明 GEM-FISH 可以胜过以前的染色体结构建模方法，并准确地捕获染色体构象的高级空间特征。此外，我们重建的染色体 3D 模型揭示了超级增强子的空间分布的有趣模式，这可以为理解这些超级增强子在基因调控中的功能作用提供有用的见解。
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