Babaei Sepideh, Mahfouz Ahmed, Hulsman Marc, Lelieveldt Boudewijn P F, de Ridder Jeroen, Reinders Marcel
Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands; Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
PLoS Comput Biol. 2015 May 12;11(5):e1004221. doi: 10.1371/journal.pcbi.1004221. eCollection 2015 May.
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).
基因组在细胞核中的三维构象影响着诸如基因表达调控等重要的生物学过程。最近的研究表明染色质相互作用与基因共表达之间存在很强的相关性。然而，从频繁的长程染色质相互作用预测基因共表达仍然具有挑战性。我们通过使用尺度感知拓扑度量来表征皮质染色质相互作用网络的拓扑结构来解决这个问题。我们证明，基于这些表征，可以准确预测小鼠皮质中基因之间的空间共表达。与之前的发现一致，我们发现基因对的染色质相互作用谱是其空间共表达的良好预测指标。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度量来描述染色质相互作用时，预测的准确性可以得到显著提高。我们得出结论，对于共表达预测，有必要考虑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）等不同水平的染色质相互作用。
