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, Walter Kolch, Olaf Wolkenhauer

Research output: Contribution to journalArticleResearchpeer-review

138 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)726-739
Number of pages14
JournalSimulation
Volume79
Issue number12
DOIs
Publication statusPublished - 1 Jan 2003
Externally publishedYes

Keywords

  • Experimental design
  • Mathematical modeling
  • Monte Carlo method
  • NF-κB
  • Parametric sensitivity
  • Signal transduction pathway
  • Systems biology
  • TNFα

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