Topological analysis of mass-balanced signaling networks: a framework to obtain network properties including crosstalk
Topological analysis of mass-balanced signaling networks: a framework to obtain network properties including crosstalk
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DOI：
10.1016/j.jtbi.2003.11.016
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发表时间：
2004-03-21
影响因子：
2
通讯作者：
Palsson, BO
中科院分区：
文献类型：
--
作者：
Papin, JA;Palsson, BO
信号转导网络只在小规模上进行了研究，因为大规模的重建和合适的计算机分析方法还没有。由于大型信令网络的重建进展顺利，现在需要开发一个框架来分析信令网络的结构特性。一个这样的框架是在这里，一个是基于系统独立的途径和信号事件的质量平衡表示。这种方法被应用于原型信令网络，并且它允许：（1）所有可能的输入/输出关系的系统分析，（2）网络串扰或系统独立通路的互连性的定量评估，（3）信号网络中冗余的测量，（4）信号通路中反应的参与，（5）关联反应集的计算。这些性质来自网络结构，只能在定义的数学框架内推导和研究。所提出的计算是信号网络的第一次，而类似的分析已经广泛地用于原型和基因组规模的代谢网络。这一方法尚未考虑到动态浓度分布。到期对于所使用的化学计量形式的可缩放性，一旦完成了大型信令网络的重构，就可以获得针对原型信令网络呈现的结果。(C)2003爱思唯尔有限公司。保留所有权利。
Signal transduction networks have only been studied at a small scale because large-scale reconstructions and suitable in silico analysis methods have not been available. Since reconstructions of large signaling networks are progressing well there is now a need to develop a framework for analysing structural properties of signaling networks. One such framework is presented here, one that is based on systemically independent pathways and a mass-balanced representation of signaling events. This approach was applied to a prototypic signaling network and it allowed for: (1) a systemic analysis of all possible input/output relationships, (2) a quantitative evaluation of network crosstalk, or the interconnectivity of systemically independent pathways, (3) a measure of the redundancy in the signaling network, (4) the participation of reactions in signaling pathways, and (5) the calculation of correlated reaction sets. These properties emerge from network structure and can only be derived and studied within a defined mathematical framework. The calculations presented are the first of their kind for a signaling network, while similar analysis has been extensively performed for prototypic and genome-scale metabolic networks. This approach does not yet account for dynamic concentration profiles. Due. to the scalability of the stoichiometric formalism used, the results presented for the prototypic signaling network can be obtained for large signaling networks once their reconstruction is completed. (C) 2003 Elsevier Ltd. All rights reserved.