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Briefings in Bioinformatics Advance Access published online on September 26, 2006
Briefings in Bioinformatics, 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
Received June 19, 2006
Accepted August 29, 2006

Original papers

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

Hidde de Jong * and Delphine Ropers

* To whom correspondence should be addressed.
Hidde de Jong, E-mail: Hidde.de-Jong{at}inrialpes.fr


  Abstract

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.

Hidde de Jong obtained MSc degrees in computer science, philosophy of science and management science from the University of Twente (the Netherlands) and completed his PhD thesis in computer science at the same university. He joined INRIA in 1998, and is currently a senior research scientist in the Helix bioinformatics group at INRIA Rhône-Alpes (Grenoble).

Delphine Ropers obtained an MSc degree in microbiology and enzymology from the Henri Poincaré University in Nancy (France). After completing a PhD thesis in structural, cellular, and molecular biology in 2003, she joined the Helix bioinformatics group at INRIA Rhône-Alpes as a post-doctoral fellow. She is currently a research scientist in the same group.


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