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Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling

When modeling cell signaling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply a fuzzy logic framework to the analysis of a large, systematic dataset describing the dynamics of cell signaling downstream of TNF, EGF, and insulin receptors...

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Detalles Bibliográficos
Autores principales: Aldridge, Bree B., Saez-Rodriguez, Julio, Muhlich, Jeremy L., Sorger, Peter K., Lauffenburger, Douglas A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663056/
https://www.ncbi.nlm.nih.gov/pubmed/19343194
http://dx.doi.org/10.1371/journal.pcbi.1000340
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author Aldridge, Bree B.
Saez-Rodriguez, Julio
Muhlich, Jeremy L.
Sorger, Peter K.
Lauffenburger, Douglas A.
author_facet Aldridge, Bree B.
Saez-Rodriguez, Julio
Muhlich, Jeremy L.
Sorger, Peter K.
Lauffenburger, Douglas A.
author_sort Aldridge, Bree B.
collection PubMed
description When modeling cell signaling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply a fuzzy logic framework to the analysis of a large, systematic dataset describing the dynamics of cell signaling downstream of TNF, EGF, and insulin receptors in human colon carcinoma cells. Simulations based on fuzzy logic recapitulate most features of the data and generate several predictions involving pathway crosstalk and regulation. We uncover a relationship between MK2 and ERK pathways that might account for the previously identified pro-survival influence of MK2. We also find unexpected inhibition of IKK following EGF treatment, possibly due to down-regulation of autocrine signaling. More generally, fuzzy logic models are flexible, able to incorporate qualitative and noisy data, and powerful enough to produce quantitative predictions and new biological insights about the operation of signaling networks.
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spelling pubmed-26630562009-04-03 Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling Aldridge, Bree B. Saez-Rodriguez, Julio Muhlich, Jeremy L. Sorger, Peter K. Lauffenburger, Douglas A. PLoS Comput Biol Research Article When modeling cell signaling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply a fuzzy logic framework to the analysis of a large, systematic dataset describing the dynamics of cell signaling downstream of TNF, EGF, and insulin receptors in human colon carcinoma cells. Simulations based on fuzzy logic recapitulate most features of the data and generate several predictions involving pathway crosstalk and regulation. We uncover a relationship between MK2 and ERK pathways that might account for the previously identified pro-survival influence of MK2. We also find unexpected inhibition of IKK following EGF treatment, possibly due to down-regulation of autocrine signaling. More generally, fuzzy logic models are flexible, able to incorporate qualitative and noisy data, and powerful enough to produce quantitative predictions and new biological insights about the operation of signaling networks. Public Library of Science 2009-04-03 /pmc/articles/PMC2663056/ /pubmed/19343194 http://dx.doi.org/10.1371/journal.pcbi.1000340 Text en Aldridge et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Aldridge, Bree B.
Saez-Rodriguez, Julio
Muhlich, Jeremy L.
Sorger, Peter K.
Lauffenburger, Douglas A.
Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
title Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
title_full Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
title_fullStr Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
title_full_unstemmed Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
title_short Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
title_sort fuzzy logic analysis of kinase pathway crosstalk in tnf/egf/insulin-induced signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663056/
https://www.ncbi.nlm.nih.gov/pubmed/19343194
http://dx.doi.org/10.1371/journal.pcbi.1000340
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