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

Ann N Y Acad Sci. 2007 Dec;1115:221-39. doi: 10.1196/annals.1407.014. Epub 2007 Oct 12.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Carrier Proteins / immunology*
  • Computer Simulation
  • DNA-Binding Proteins
  • Gene Expression / immunology
  • I-kappa B Proteins / immunology*
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Models, Immunological*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / immunology*
  • Nuclear Proteins / immunology*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Signal Transduction / immunology*
  • Transcriptional Elongation Factors
  • Tumor Necrosis Factor alpha-Induced Protein 3


  • Carrier Proteins
  • DNA-Binding Proteins
  • Elp1 protein, human
  • I-kappa B Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nuclear Proteins
  • Transcriptional Elongation Factors
  • NF-KappaB Inhibitor alpha
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3