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

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arxiv 1010.1755 v1 pith:JCL6NWUH submitted 2010-10-08 q-bio.QM q-bio.MNq-bio.SC

classification q-bio.QMq-bio.MNq-bio.SC
keywords kappanetworkalphasignalingclusterscomputationaldifferentikk-nf-
verification ladder T0 review T1 audit T2 compute T3 formal
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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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