MOCHI enables discovery of heterogeneous interactome modules in 3D nucleome

MOCHI enables discovery of heterogeneous interactome modules in 3D nucleome
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MOCHI 能够发现 3D 核组中的异质相互作用组模块

DOI:
10.1101/gr.250316.119
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发表时间:
2020
期刊:
影响因子:
7
通讯作者:
Ma, Jian
Ma, Jian
中科院分区:
生物学1区
文献类型:
--
作者:
Tian, Dechao;Zhang, Ruochi;Zhang, Yang;Zhu, Xiaopeng;Ma, Jian

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细胞核的组成是高度异质性的,不同的成分形成复杂的相互作用体。然而,这些相互交织的异质相互作用组的全球模式仍然知之甚少。在这里,我们专注于两个不同的相互作用组,染色质相互作用网络和基因调控网络,作为一个原则的证明,以确定异质性相互作用组模块(希姆斯),其中每一个代表了一个集群的基因位点,在空间上的接触比预期的更频繁,这是由同一组的转录因子调控。HIM整合了转录因子结合和3D基因组结构,以反映细胞核中的“转录生态位”。我们开发了一个新的算法,MOCHI,以促进发现希姆斯的基础上网络模体聚类异构相互作用组。通过将MOCHI应用于五种不同的细胞类型,我们发现希姆斯在细胞核内具有强烈的空间偏好,并显示出不同的功能特性。通过综合分析,这项工作显示了MOCHI识别希姆斯的实用性,这可能为转录调控和3D基因组组织之间的相互作用提供新的视角。
The composition of the cell nucleus is highly heterogeneous, with different constituents forming complex interactomes. However, the global patterns of these interwoven heterogeneous interactomes remain poorly understood. Here we focus on two different interactomes, chromatin interaction network and gene regulatory network, as a proof of principle to identify heterogeneous interactome modules (HIMs), each of which represents a cluster of gene loci that is in spatial contact more frequently than expected and that is regulated by the same group of transcription factors. HIM integrates transcription factor binding and 3D genome structure to reflect “transcriptional niche” in the nucleus. We develop a new algorithm, MOCHI, to facilitate the discovery of HIMs based on network motif clustering in heterogeneous interactomes. By applying MOCHI to five different cell types, we found that HIMs have strong spatial preference within the nucleus and show distinct functional properties. Through integrative analysis, this work shows the utility of MOCHI to identify HIMs, which may provide new perspectives on the interplay between transcriptional regulation and 3D genome organization.
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