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Briefings in Bioinformatics Advance Access originally published online on September 26, 2006
Briefings in Bioinformatics 2006 7(4):354-363; doi:10.1093/bib/bbl034
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© The Author 2006. Published by Oxford University Press. For Permissions, please email: journals.permissions@oxfordjournals.org

Strategies for dealing with incomplete information in the modeling of molecular interaction networks

Hidde de Jong and Delphine Ropers

Corresponding author. Hidde de Jong, INRIA Rhône-Alpes, 655 avenue de l’Europe, Montbonnot, 38334 Saint Ismier Cedex, France. E-mail: Hidde.de-Jong{at}inrialpes.fr

Modelers of molecular interaction networks encounter the paradoxical situation that while large amounts of data are available, these are often insufficient for the formulation and analysis of mathematical models describing the network dynamics. In particular, information on the reaction mechanisms and numerical values of kinetic parameters are usually not available for all but a few well-studied model systems. In this article we review two strategies that have been proposed for dealing with incomplete information in the study of molecular interaction networks: parameter sensitivity analysis and model simplification. These strategies are based on the biologically justified intuition that essential properties of the system dynamics are robust against moderate changes in the value of kinetic parameters or even in the rate laws describing the interactions. Although advanced measurement techniques can be expected to relieve the problem of incomplete information to some extent, the strategies discussed in this article will retain their interest as tools providing an initial characterization of essential properties of the network dynamics.

Keywords: molecular interaction networks, incomplete information, mathematical modeling and computer simulation, kinetic models, robustness, parameter sensitivity, model simplification, piecewise-linear differential equations, Boolean models


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