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Sensitivity analysis of a computational model of the IKK-NF-{\kappa}B-I{\kappa}B{\alpha}-A20 signal transduction network

Authors
  • Joo, Jaewook
  • Plimpton, Steve
  • Martin, Shawn
  • Swiler, Laura
  • Faulon, Jean-Loup
Type
Published Article
Publication Date
Oct 08, 2010
Submission Date
Oct 08, 2010
Identifiers
DOI: 10.1196/annals.1407.014
Source
arXiv
License
Yellow
External links

Abstract

The NF-{\kappa}B signaling network plays an important role in many different compartments of the immune system during immune activation. Using a computational model of the NF-{\kappa}B signaling network involving two negative regulators, I{\kappa}B{\alpha} and A20, we performed sensitivity analyses with three different sampling methods and present a ranking of the kinetic rate variables by the strength of their influence on the NF-{\kappa}B signaling response. We also present a classification of temporal response profiles of nuclear NF-{\kappa}B concentration into six clusters, which can be regrouped to three biologically relevant clusters. Lastly, based upon the ranking, we constructed a reduced network of the IKK-NF-{\kappa}B-I{\kappa}B{\alpha}-A20 signal transduction.

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