title: Sensitivity analysis of a computational model of the IKK NF-kappaB IkappaBalpha A20 signal transduction network.
abstract: 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.
authors.affiliation: Department of Computational Biosciences, Sandia National Laboratories, P.O. Box 5800 Albuquerque, NM 87185-1413, USA. jjoo@sandia.gov
authors.forename: Jaewook
authors.initials: J
authors.lastname: Joo
authors.forename: Steve
authors.initials: S
authors.lastname: Plimpton
authors.forename: Shawn
authors.initials: S
authors.lastname: Martin
authors.forename: Laura
authors.initials: L
authors.lastname: Swiler
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Faulon
mesh_terms: D000465:Algorithms; D002352:Carrier Proteins / Q000276:immunology*; D003198:Computer Simulation; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000276:immunology; D020672:I-kappa B Proteins / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D018448:Models, Immunological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000276:immunology*; D035602:Transcriptional Elongation Factors; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C114720:Elp1 protein, human; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D035602:Transcriptional Elongation Factors; D000072000:NF-KappaB Inhibitor alpha; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3