Sensitivity Analysis of a Computational Model of the IKK-NF-kB-A20 Signal Transduction Network
J. Joo, S. J. Plimpton, S. Martin, L. Swiler, J. L. Faulon, Annals of the New York Acadamey of Sciences, Volume on Reverse Engineering Biological Networks, 1115, 221-239 (2007).
The NF-kB signaling network plays an important role in many different compartments of the immune system during immune activation. Using a computational model of the NF-kB signaling network involving two negative regulators, IkB 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-kB signaling response. We also present a classif ication of temporal-response profiles of nuclear NF-kB concentration into six clusters, which can be regrouped to three biologically relevant clusters. Last, we constructed a reduced network of the IKK-NF-kB-A20 signal transduction based on the ranking.
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