Experimental Design In Systems Biology, Based On Parameter Sensitivity Analysis Using A Monte Carlo Method: A Case Study For The Tnfa-Mediated NF-?b Signal Transduction Pathway  

Oleh:

Cho, Kwang-Hyun ; Shin, Sung-Young ; Kolch, Walter ; Wolkenhauer, Olaf

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Simulation vol. 79 no. 12 (Dec. 2003), page 726-739.
Topik: Systems biology; experimental design; signal transduction pathway; mathematical modeling; parametric sensitivity; Monte Carlo method; TNFa; NF-?B
Fulltext: 726.pdf (811.34KB)

Isi artikel

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 TNFa-mediated NF-?B 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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