Topological analysis of mass-balanced signaling networks: A framework to obtain network properties including crosstalk

Jason A. Papin, Bernhard O. Palsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)283-297
Number of pages15
JournalJournal of Theoretical Biology
Volume227
Issue number2
DOIs
Publication statusPublished - 21 Mar 2004

Bibliographical note

Funding Information:
We thank Shankar Subramaniam for a critical reading of the manuscript. We also acknowledge financial support from the National Institutes of Health (GM 068837) and the Whitaker Foundation (Graduate Research Fellowship to JP).

Other keywords

  • Constraint-based modeling
  • Crosstalk
  • Extreme pathways
  • Network-based pathways
  • Signal transduction

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