Sensitivity analysis and robust experimental design of a signal transduction pathway system

Hong Yue, Martin Brown, Fei He, Jianfang Jia, Douglas B. Kell

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Experimental design for cellular networks based on sensitivity analysis is studied in this work. Both optimal and robust experimental design strategies are developed for the IKB-NF-κB signal transduction model. Based on local sensitivity analysis, the initial IKK intensity is calculated using an optimal experimental design process, and several scalarization measures of the Fisher information matrix are compared. Global sensitivity analysis and robust experimental design techniques are then developed to consider parametric uncertainties in the model. The modified Morris method is employed in global sensitivity analysis, and a semidefinite Programm ing method is exploited to implement the robust experimental design for the problem of measurement set selection. The parametric impacts on the oscillatory behavior of NF-κB in the nucleus are also discussed.

Original languageEnglish
Pages (from-to)730-741
Number of pages12
JournalInternational Journal of Chemical Kinetics
Volume40
Issue number11
Early online date12 Sept 2008
DOIs
Publication statusPublished - 1 Nov 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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