Sensitivity analysis of a computational model of the IKK NF-kappaB IkappaBalpha A20 signal transduction network.

The NF-kappaB signaling network plays an important role in many different compartments of the immune system during immune activation. Using a computational model of the NF-kappaB signaling network involving two negative regulators, IkappaBalpha 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-kappaB signaling response. We also present a classification of temporal-response profiles of nuclear NF-kappaB concentration into six clusters, which can be regrouped to three biologically relevant clusters. Last, we constructed a reduced network of the IKK-NF-kappaB-IkappaBalpha-A20 signal transduction based on the ranking.