Global sensitivity analysis of cell signaling transduction networks based on latin hypercube sampling method

J.F. Jia; H. Yue; T.Y. Liu; H. Wang

Global sensitivity analysis of cell signaling transduction networks based on latin hypercube sampling method

J.F. Jia, H. Yue, T.Y. Liu, H. Wang

Electronic And Electrical Engineering

Research output: Contribution to conference › Paper › peer-review

Abstract

The dynamic behavior of a cell model is affected by its structural complexity and parametric uncertainties. Two important issues in systems biology are how to quantitatively determine the relationship between system behaviors and parameter
variations, and how to study the interactions between parameters. Using an NF-κB signaling pathway model as an example, and assuming that the parameters of this model are independent of each other and obey the identical uniform distribution in the
range of variations, the global sensitivity analysis on the system output of NF-κB in the nucleus with respect to parameters is studied by means of the Latin hypercube sampling method. Simulation results demonstrate that the oscillation behavior of the concentration of NF-κB in the nucleus is sensitive to 6 key rate constants, which relates to reactions of IκBα mRNA degradation, IκBα inducible mRNA synthesis, IKK adaption, constitutive IκBα mRNA translation, IKK-IκBα NF-κB association, and IκBβ mRNA degradation, respectively.

Original language	English
Pages	434-437
Number of pages	4
Publication status	Published - 2007
Event	The 1st International Conference on Bioinformatics and Biomedical Engineering - Wuhan, China Duration: 6 Jul 2007 → 8 Jul 2007

Conference

Conference	The 1st International Conference on Bioinformatics and Biomedical Engineering
Country	China
City	Wuhan
Period	6/07/07 → 8/07/07

Keywords

cell signaling transduction
latin hypercube sampling
global sensitivity

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@conference{77f3b246addc47fbb308b3f908943682,

title = "Global sensitivity analysis of cell signaling transduction networks based on latin hypercube sampling method",

abstract = "The dynamic behavior of a cell model is affected by its structural complexity and parametric uncertainties. Two important issues in systems biology are how to quantitatively determine the relationship between system behaviors and parametervariations, and how to study the interactions between parameters. Using an NF-κB signaling pathway model as an example, and assuming that the parameters of this model are independent of each other and obey the identical uniform distribution in therange of variations, the global sensitivity analysis on the system output of NF-κB in the nucleus with respect to parameters is studied by means of the Latin hypercube sampling method. Simulation results demonstrate that the oscillation behavior of the concentration of NF-κB in the nucleus is sensitive to 6 key rate constants, which relates to reactions of IκBα mRNA degradation, IκBα inducible mRNA synthesis, IKK adaption, constitutive IκBα mRNA translation, IKK-IκBα NF-κB association, and IκBβ mRNA degradation, respectively.",

keywords = "cell signaling transduction, latin hypercube sampling, global sensitivity",

author = "J.F. Jia and H. Yue and T.Y. Liu and H. Wang",

year = "2007",

language = "English",

pages = "434--437",

note = "The 1st International Conference on Bioinformatics and Biomedical Engineering ; Conference date: 06-07-2007 Through 08-07-2007",

}

TY - CONF

T1 - Global sensitivity analysis of cell signaling transduction networks based on latin hypercube sampling method

AU - Jia, J.F.

AU - Yue, H.

AU - Liu, T.Y.

AU - Wang, H.

PY - 2007

Y1 - 2007

N2 - The dynamic behavior of a cell model is affected by its structural complexity and parametric uncertainties. Two important issues in systems biology are how to quantitatively determine the relationship between system behaviors and parametervariations, and how to study the interactions between parameters. Using an NF-κB signaling pathway model as an example, and assuming that the parameters of this model are independent of each other and obey the identical uniform distribution in therange of variations, the global sensitivity analysis on the system output of NF-κB in the nucleus with respect to parameters is studied by means of the Latin hypercube sampling method. Simulation results demonstrate that the oscillation behavior of the concentration of NF-κB in the nucleus is sensitive to 6 key rate constants, which relates to reactions of IκBα mRNA degradation, IκBα inducible mRNA synthesis, IKK adaption, constitutive IκBα mRNA translation, IKK-IκBα NF-κB association, and IκBβ mRNA degradation, respectively.

AB - The dynamic behavior of a cell model is affected by its structural complexity and parametric uncertainties. Two important issues in systems biology are how to quantitatively determine the relationship between system behaviors and parametervariations, and how to study the interactions between parameters. Using an NF-κB signaling pathway model as an example, and assuming that the parameters of this model are independent of each other and obey the identical uniform distribution in therange of variations, the global sensitivity analysis on the system output of NF-κB in the nucleus with respect to parameters is studied by means of the Latin hypercube sampling method. Simulation results demonstrate that the oscillation behavior of the concentration of NF-κB in the nucleus is sensitive to 6 key rate constants, which relates to reactions of IκBα mRNA degradation, IκBα inducible mRNA synthesis, IKK adaption, constitutive IκBα mRNA translation, IKK-IκBα NF-κB association, and IκBβ mRNA degradation, respectively.

KW - cell signaling transduction

KW - latin hypercube sampling

KW - global sensitivity

M3 - Paper

SP - 434

EP - 437

T2 - The 1st International Conference on Bioinformatics and Biomedical Engineering

Y2 - 6 July 2007 through 8 July 2007

ER -