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基于微阵列数据的网络鲁棒性和响应能力的新测量方法。

New measurement methods of network robustness and response ability via microarray data.

机构信息

Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan.

出版信息

PLoS One. 2013;8(1):e55230. doi: 10.1371/journal.pone.0055230. Epub 2013 Jan 28.

Abstract

"Robustness", the network ability to maintain systematic performance in the face of intrinsic perturbations, and "response ability", the network ability to respond to external stimuli or transduce them to downstream regulators, are two important complementary system characteristics that must be considered when discussing biological system performance. However, at present, these features cannot be measured directly for all network components in an experimental procedure. Therefore, we present two novel systematic measurement methods--Network Robustness Measurement (NRM) and Response Ability Measurement (RAM)--to estimate the network robustness and response ability of a gene regulatory network (GRN) or protein-protein interaction network (PPIN) based on the dynamic network model constructed by the corresponding microarray data. We demonstrate the efficiency of NRM and RAM in analyzing GRNs and PPINs, respectively, by considering aging- and cancer-related datasets. When applied to an aging-related GRN, our results indicate that such a network is more robust to intrinsic perturbations in the elderly than in the young, and is therefore less responsive to external stimuli. When applied to a PPIN of fibroblast and HeLa cells, we observe that the network of cancer cells possesses better robustness than that of normal cells. Moreover, the response ability of the PPIN calculated from the cancer cells is lower than that from healthy cells. Accordingly, we propose that generalized NRM and RAM methods represent effective tools for exploring and analyzing different systems-level dynamical properties via microarray data. Making use of such properties can facilitate prediction and application, providing useful information on clinical strategy, drug target selection, and design specifications of synthetic biology from a systems biology perspective.

摘要

“鲁棒性”是指网络在面对内在扰动时维持系统性能的能力,“响应能力”是指网络对外界刺激做出响应或将其转化为下游调节剂的能力,这是讨论生物系统性能时必须考虑的两个重要的互补系统特征。然而,目前,在实验过程中,无法直接测量所有网络组件的这两个特性。因此,我们提出了两种新的系统测量方法——网络鲁棒性测量(NRM)和响应能力测量(RAM)——来根据相应的微阵列数据构建的动态网络模型来估计基因调控网络(GRN)或蛋白质-蛋白质相互作用网络(PPIN)的网络鲁棒性和响应能力。我们通过考虑与衰老和癌症相关的数据集,分别展示了 NRM 和 RAM 在分析 GRN 和 PPIN 中的效率。当应用于与衰老相关的 GRN 时,我们的结果表明,与年轻人相比,老年人的网络对内在扰动更具鲁棒性,因此对外界刺激的响应能力较低。当应用于成纤维细胞和 HeLa 细胞的 PPIN 时,我们观察到癌细胞的网络比正常细胞具有更好的鲁棒性。此外,从癌细胞计算出的 PPIN 的响应能力低于从健康细胞计算出的响应能力。因此,我们提出了广义的 NRM 和 RAM 方法,这些方法代表了通过微阵列数据探索和分析不同系统级动态特性的有效工具。利用这些特性可以促进预测和应用,从系统生物学的角度为临床策略、药物靶点选择和合成生物学的设计规范提供有用的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5b3/3557243/4270ac6e1e43/pone.0055230.g001.jpg

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