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信号网络进行的噪声处理

Noise-processing by signaling networks.

作者信息

Kontogeorgaki Styliani, Sánchez-García Rubén J, Ewing Rob M, Zygalakis Konstantinos C, MacArthur Ben D

机构信息

Mathematical Sciences, University of Southampton, SO17 1BJ, Southampton, UK.

Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.

出版信息

Sci Rep. 2017 Apr 3;7(1):532. doi: 10.1038/s41598-017-00659-x.

Abstract

Signaling networks mediate environmental information to the cell nucleus. To perform this task effectively they must be able to integrate multiple stimuli and distinguish persistent signals from transient environmental fluctuations. However, the ways in which signaling networks process environmental noise are not well understood. Here we outline a mathematical framework that relates a network's structure to its capacity to process noise, and use this framework to dissect the noise-processing ability of signaling networks. We find that complex networks that are dense in directed paths are poor noise processors, while those that are sparse and strongly directional process noise well. These results suggest that while cross-talk between signaling pathways may increase the ability of signaling networks to integrate multiple stimuli, too much cross-talk may compromise the ability of the network to distinguish signal from noise. To illustrate these general results we consider the structure of the signalling network that maintains pluripotency in mouse embryonic stem cells, and find an incoherent feedforward loop structure involving Stat3, Tfcp2l1, Esrrb, Klf2 and Klf4 is particularly important for noise-processing. Taken together these results suggest that noise-processing is an important function of signaling networks and they may be structured in part to optimize this task.

摘要

信号网络将环境信息传递至细胞核。为有效执行此任务,它们必须能够整合多种刺激,并区分持续信号与短暂的环境波动。然而,信号网络处理环境噪声的方式尚不清楚。在此,我们概述了一个将网络结构与其处理噪声的能力相关联的数学框架,并使用该框架剖析信号网络的噪声处理能力。我们发现,有向路径密集的复杂网络是较差的噪声处理器,而稀疏且具有强方向性的网络则能很好地处理噪声。这些结果表明,虽然信号通路之间的串扰可能会增强信号网络整合多种刺激的能力,但过多的串扰可能会损害网络区分信号与噪声的能力。为说明这些一般性结果,我们考虑了维持小鼠胚胎干细胞多能性的信号网络结构,发现涉及Stat3、Tfcp2l1、Esrrb、Klf2和Klf4的非相干前馈环结构对于噪声处理尤为重要。综合这些结果表明,噪声处理是信号网络的一项重要功能,并且它们的结构可能部分是为了优化此任务。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2d1/5428852/831c0ae04a4d/41598_2017_659_Fig1_HTML.jpg

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