Journal
SIMULATION-TRANSACTIONS OF THE SOCIETY FOR MODELING AND SIMULATION INTERNATIONAL
Volume 79, Issue 12, Pages 726-739Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0037549703040943
Keywords
systems biology; experimental design; signal transduction pathway; mathematical modeling; parametric sensitivity; Monte Carlo method; TNF alpha; NF-kappa B
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Mathematical modeling and dynamic simulation of signal transduction pathways is a central theme in systems biology and is increasingly attracting attention in the postgenomic era. The estimation of model parameters from experimental data remains a bottleneck for a major breakthrough in this area. This study's aim is to introduce a new strategy for experimental design based on parameter sensitivity analysis. The approach identifies key parameters/variables in a signal transduction pathway model and can thereby provide experimental biologists with guidance on which proteins to consider for measurement. The article focuses on applying this approach to the TNFalpha-mediated NF-kappaB pathway, which plays an important role in immunity and inflammation and in the control of cell proliferation, differentiation, and apoptosis. A mathematical model of this pathway is proposed, and the sensitivity analysis of model parameters is illustrated for this model by employing the Monte Carlo method over a broad range of parameter values.
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