Guarnera Enrico, Tan Zhen Wah, Berezovsky Igor N
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 30 Biopolis Street, #07-01, Matrix, Singapore 138671, Singapore.
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A(∗)STAR), 30 Biopolis Street, #07-01, Matrix, Singapore 138671, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 8 Medical Drive, Singapore 117597, Singapore.
Structure. 2021 Jun 3;29(6):622-634.e3. doi: 10.1016/j.str.2021.01.008. Epub 2021 Feb 9.
We propose a comprehensive method for reconstructing the whole-genome chromatin ensemble from the Hi-C data. The procedure starts from Markov state modeling (MSM), delineating the structural hierarchy of chromatin organization with partitioning and effective interactions archetypal for corresponding levels of hierarchy. The stochastic embedding procedure introduced in this work provides the 3D ensemble reconstruction, using effective interactions obtained by the MSM as the input. As a result, we obtain the structural ensemble of a genome, allowing one to model the functional and the cell-type variability in the chromatin structure. The whole-genome reconstructions performed on the human B lymphoblastoid (GM12878) and lung fibroblast (IMR90) Hi-C data unravel distinctions in their morphologies and in the spatial arrangement of intermingling chromosomal territories, paving the way to studies of chromatin dynamics, developmental changes, and conformational transitions taking place in normal cells and during potential pathological developments.
我们提出了一种从Hi-C数据重建全基因组染色质整体结构的综合方法。该过程从马尔可夫状态建模（MSM）开始，通过划分和对应层次结构水平的有效相互作用原型来描绘染色质组织的结构层次。本工作中引入的随机嵌入过程利用MSM获得的有效相互作用作为输入，提供三维整体结构重建。结果，我们获得了基因组的结构整体，从而能够对染色质结构中的功能和细胞类型变异性进行建模。对人类B淋巴母细胞（GM12878）和肺成纤维细胞（IMR90）的Hi-C数据进行的全基因组重建揭示了它们形态以及相互交织的染色体区域空间排列上的差异，为研究正常细胞以及潜在病理发展过程中发生的染色质动力学、发育变化和构象转变铺平了道路。
