Sensitivity Analysis of a Computational Model of the IKK–NF-κB–IκBα–A20 Signal Transduction Network

Abstract

Abstract: 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. Last, we constructed a reduced network of the IKK–NF-κB–IκBα–A20 signal transduction based on the ranking.