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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Algorithms*
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Carrier Proteins / immunology*
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Computer Simulation
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DNA-Binding Proteins
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Gene Expression / immunology
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I-kappa B Proteins / immunology*
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Intracellular Signaling Peptides and Proteins / immunology*
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Models, Immunological*
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NF-KappaB Inhibitor alpha
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NF-kappa B / immunology*
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Nuclear Proteins / immunology*
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Reproducibility of Results
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Sensitivity and Specificity
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Signal Transduction / immunology*
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Transcriptional Elongation Factors
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Tumor Necrosis Factor alpha-Induced Protein 3
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Elp1 protein, human
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I-kappa B Proteins
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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NFKBIA protein, human
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Nuclear Proteins
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Transcriptional Elongation Factors
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NF-KappaB Inhibitor alpha
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TNFAIP3 protein, human
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Tumor Necrosis Factor alpha-Induced Protein 3