Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 227, Issue 2, Pages 283-297Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2003.11.016
Keywords
signal transduction; network-based pathways; constraint-based modeling; extreme pathways; crosstalk
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Funding
- NIGMS NIH HHS [GM068837] Funding Source: Medline
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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.
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