Decoding topologically associating domains with ultra-low resolution Hi-C data by graph structural entropy.

Decoding topologically associating domains with ultra-low resolution Hi-C data by graph structural entropy.
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通过图结构熵解码具有超低分辨率 Hi-C 数据的拓扑关联域

DOI:
10.1038/s41467-018-05691-7
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发表时间:
2018-08-15
影响因子:
16.6
通讯作者:
Zhang Z
Zhang Z
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li A;Yin X;Xu B;Wang D;Han J;Wei Y;Deng Y;Xiong Y;Zhang Z

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在高通量染色质相互作用数据(Hi-C)中观察到亚兆酶大小的拓扑相关结构域(TAD)。然而,TADs的准确检测依赖于超深度测序和复杂的归一化程序。本文提出了一种基于结构信息理论的快速、无归一化的染色体域解码方法(deDoc)。通过将Hi-C接触矩阵作为图的表示,deDoc将图划分为结构熵最小的段。我们表明,结构熵也可以用来确定适当的桶大小的Hi-C数据。通过将deDoc应用于来自10个单细胞的池化Hi-C数据,我们检测到兆级大小的类tad结构域。这一结果表明,基因组空间组织的模块化结构可能是基本的,甚至一个小队列的单细胞。我们的算法可能有助于在更大的范围内对染色体结构域进行系统的研究。TADs的准确检测需要超深测序和复杂的归一化程序,这限制了对Hi-C数据的分析。在这里,作者开发了一种无归一化的方法来解码染色体结构域(deDoc),该方法利用结构熵来预测具有超低测序数据的tad。
Submegabase-size topologically associating domains (TAD) have been observed in high-throughput chromatin interaction data (Hi-C). However, accurate detection of TADs depends on ultra-deep sequencing and sophisticated normalization procedures. Here we propose a fast and normalization-free method to decode the domains of chromosomes (deDoc) that utilizes structural information theory. By treating Hi-C contact matrix as a representation of a graph, deDoc partitions the graph into segments with minimal structural entropy. We show that structural entropy can also be used to determine the proper bin size of the Hi-C data. By applying deDoc to pooled Hi-C data from 10 single cells, we detect megabase-size TAD-like domains. This result implies that the modular structure of the genome spatial organization may be fundamental to even a small cohort of single cells. Our algorithms may facilitate systematic investigations of chromosomal domains on a larger scale than hitherto have been possible. Accurate detection of TADs requires ultra-deep sequencing and sophisticated normalisation procedures, which limits the analysis of Hi-C data. Here the authors develop a normalisation-free method to decode the domains of chromosomes (deDoc) that utilizes structural entropy to predict TADs with ultra-low sequencing data.
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