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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Autores principales:	Bree B Aldridge, Julio Saez-Rodriguez, Jeremy L Muhlich, Peter K Sorger, Douglas A Lauffenburger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/34f6dc7f8af2479fa4f3cfbd328bbd55
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spelling	oai:doaj.org-article:34f6dc7f8af2479fa4f3cfbd328bbd552021-11-25T05:41:45ZFuzzy logic analysis of kinase pathway crosstalk in TNF/EGF/insulin-induced signaling.1553-734X1553-735810.1371/journal.pcbi.1000340https://doaj.org/article/34f6dc7f8af2479fa4f3cfbd328bbd552009-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19343194/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358When 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.Bree B AldridgeJulio Saez-RodriguezJeremy L MuhlichPeter K SorgerDouglas A LauffenburgerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 4, p e1000340 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Bree B Aldridge Julio Saez-Rodriguez Jeremy L Muhlich Peter K Sorger Douglas A Lauffenburger Fuzzy logic analysis of kinase pathway crosstalk in TNF/EGF/insulin-induced signaling.
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.
format	article
author	Bree B Aldridge Julio Saez-Rodriguez Jeremy L Muhlich Peter K Sorger Douglas A Lauffenburger
author_facet	Bree B Aldridge Julio Saez-Rodriguez Jeremy L Muhlich Peter K Sorger Douglas A Lauffenburger
author_sort	Bree B Aldridge
title	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_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_sort	fuzzy logic analysis of kinase pathway crosstalk in tnf/egf/insulin-induced signaling.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/34f6dc7f8af2479fa4f3cfbd328bbd55
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Fuzzy logic analysis of kinase pathway crosstalk in TNF/EGF/insulin-induced signaling.

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