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Kwang-Hyun Cho, Sung-Young Shin, Walter Kolch, Olaf Wokenhauer: Experimental Design in Systems Biology, Based on Parameter Sensitivity Analysis Using a Monte Carlo Method: a Case Study for the TNFα-Mediated NF-κB Signal Transduction Pathway.

From: SIMULATION, Vol. 79, Issue 12, December 2003.

Abstract: 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 TNFα-mediated NF-κB 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.

Keywords: Systems biology, experimental design, signal transduction pathway, mathematical modeling, parametric sensitivity, Monte Carlo method, TNFα, NF-κB

The article can be downloaded from cho04a-sensitivity

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