文档介绍：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
Kwang-Hyun Cho
Sung-Young Shin
School of Electrical Engineering
University of Ulsan
Ulsan, 680-749, Korea
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Walter Kolch
Beatson Institute for Cancer Research
Cancer Research UK
Beatson Laboratories
Switchback Road, Glasgow, G61 1BD, United Kingdom
Institute of Biomedical and Life Sciences
University of Glasgow
University Avenue, Glasgow, G12 8QQ, United Kingdom
Olaf Wolkenhauer
Department puter Science
University of Rostock, Albert Einstein Str. 21
18059 Rostock, Germany
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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 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 mod-
eling, parametric sensitivity, Monte Carlo method, TNFα, NF-κB
1. Introduction not due to particular biological breakt