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Sensitivity analysis of a computational model of the IKK-NF-κB-IκBα-A20 signal transduction network

The NF-κB signaling network plays an important role in many different compartments of the immune system during immune activation. Using a computational model of the NF-κB signaling network involving two negative regulators, IκBα 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-κB signaling response. We also present a classification of temporal response profiles of nuclear NF-κB 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-κB-IκBα-A20 signal transduction.

preprint2010arXivOpen access

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