Modular response analysis of cellular regulatory networks
Modular response analysis of cellular regulatory networks
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DOI：
10.1006/jtbi.2002.3096
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发表时间：
2002-10-21
影响因子：
2
通讯作者：
Kholodenko, BN
中科院分区：
文献类型：
--
作者：
Bruggeman, FJ;Westerhoff, HV;Kholodenko, BN
细胞内调控网络的绝对复杂性，涉及信号转导、代谢和遗传电路，阻碍了我们对其功能进行量化分析的能力。在这里，我们描述了一种方法，它通过利用此类网络的模块化组织极大地简化了此类分析。整个网络的稳态响应仅从模块间相互作用的角度考虑；在分析整个网络中的信号传输时，不需要考虑仅在模块内运行的过程。模块间的交互作用通过填充交互作用图(矩阵)的(本地)响应系数来量化。这个矩阵可以从构成调控网络的(宏观)分子相互作用的生化或分子生物学分析中获得。该方法通过两个例子来说明：(I)通过表皮生长因子受体网络中有丝分裂原激活的蛋白激酶级联传递有丝分裂信号；(Ii)调节大肠杆菌中的氨同化。(C)2002爱思唯尔科学有限公司。保留所有权利。
The sheer complexity of intracellular regulatory networks, which involve signal transducing, metabolic, and genetic circuits, hampers our ability to carry out a quantitative analysis of their functions. Here, we describe an approach that greatly simplifies this type of analysis by capitalizing on the modular organization of such networks. Steady-state responses of the network as a whole are accounted for in, terms of intermodular interactions between the modules alone; processes operating solely within modules need not be considered when analysing signal transfer through the entire network. The intermodular interactions are quantified through (local) response coefficients which populate an interaction map (matrix). This matrix can be derived from a biochemical or molecular biological analysis of (macro) molecular interactions that constitute the regulatory network. The approach is illustrated by two examples: (i) mitogenic signalling through the mitogen-activated protein kinase cascade in the epidermal growth factor receptor network and (ii) regulation of ammonium assimilation in Escherichia coli. (C) 2002 Elsevier Science Ltd. All rights reserved.