Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex.

Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex.
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HI-C染色质相互作用网络预测小鼠皮质中的共表达。

DOI:
10.1371/journal.pcbi.1004221
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发表时间:
2015-05
影响因子:
4.3
通讯作者:
Reinders M
Reinders M
中科院分区:
生物学2区
文献类型:
--
作者:
Babaei S;Mahfouz A;Hulsman M;Lelieveldt BP;de Ridder J;Reinders M

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细胞核中基因组的三维构象影响重要的生物学过程,如基因表达调控。最近的研究表明,染色质相互作用和基因共表达之间有很强的相关性。然而,从频繁的长距离染色质相互作用预测基因共表达仍然具有挑战性。我们解决这一问题的特征的皮质染色质相互作用网络的拓扑结构,使用尺度感知的拓扑措施。我们证明,基于这些特征,它是可能的,以准确地预测小鼠大脑皮层中的基因之间的空间共表达。与以前的研究结果一致,我们发现,染色质相互作用的基因对是一个很好的预测其空间共表达。然而,当使用多分辨率染色质相互作用网络的尺度感知拓扑测量来描述染色质相互作用时,预测的准确性可以得到实质性的提高。我们的结论是,对于共表达预测,有必要考虑不同水平的染色质相互作用,从基因之间的直接相互作用(即小规模)到染色质区室相互作用(即大规模)。调控元件可以通过长距离染色质相互作用靶向大基因组距离的基因。这些相互作用是由于细胞核中染色体的三维(3D)构象而产生的。这种3D构象也可以导致共调节基因的共定位。为了研究这一点,我们询问了全基因组染色质相互作用是否可以预测基因的共表达模式。为了解决这个问题,我们通过一个称为染色质相互作用网络(CIN)的网络表征了Hi-C测量捕获的基因之间的3D相互作用。我们将尺度感知拓扑度量应用于网络,以全面表征不同尺度下的染色质相互作用,从基因对之间的直接相互作用到染色质区室相互作用。然后,我们使用多尺度染色质相互作用来预测小鼠皮层中的空间共表达模式。结果表明,当使用多分辨率染色质相互作用网络的尺度感知拓扑测度时,预测性能得到改善。
The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale). Regulatory elements can target genes over large genomic distances through long-range chromatin interactions. These interactions arise as a result of the three-dimensional (3D) conformation of chromosomes in the cell nucleus. This 3D conformation can also result in the co-localization of co-regulated genes. To investigate this, we asked whether genome-wide chromatin interactions can predict co-expression patterns of genes. To address this question, we characterized 3D interactions between genes, captured by Hi-C measurements, by a network, termed chromatin interaction network (CIN). We applied scale-aware topological measures to the network to comprehensively characterize the chromatin interactions at different scales, ranging from direct interaction between gene pairs to chromatin compartment interactions. We then used multi-scale chromatin interactions to predict spatial co-expression patterns in the mouse cortex. The results show that the prediction performance improves when scale-aware topological measures of the multi-resolution chromatin interaction network are used.
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