Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.

Physicochemical models of signaling pathways are characterized by high levels of structural and parametric uncertainty, reflecting both incomplete knowledge about signal transduction and the intrinsic variability of cellular processes. As a result, these models try to predict the dynamics of systems...

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Autores principales:	Liang Qiao, Robert B Nachbar, Ioannis G Kevrekidis, Stanislav Y Shvartsman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bfb39b0aeb3444ffa4ca80d07d39c2c3
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spelling	oai:doaj.org-article:bfb39b0aeb3444ffa4ca80d07d39c2c32021-11-25T05:41:06ZBistability and oscillations in the Huang-Ferrell model of MAPK signaling.1553-734X1553-735810.1371/journal.pcbi.0030184https://doaj.org/article/bfb39b0aeb3444ffa4ca80d07d39c2c32007-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.0030184https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Physicochemical models of signaling pathways are characterized by high levels of structural and parametric uncertainty, reflecting both incomplete knowledge about signal transduction and the intrinsic variability of cellular processes. As a result, these models try to predict the dynamics of systems with tens or even hundreds of free parameters. At this level of uncertainty, model analysis should emphasize statistics of systems-level properties, rather than the detailed structure of solutions or boundaries separating different dynamic regimes. Based on the combination of random parameter search and continuation algorithms, we developed a methodology for the statistical analysis of mechanistic signaling models. In applying it to the well-studied MAPK cascade model, we discovered a large region of oscillations and explained their emergence from single-stage bistability. The surprising abundance of strongly nonlinear (oscillatory and bistable) input/output maps revealed by our analysis may be one of the reasons why the MAPK cascade in vivo is embedded in more complex regulatory structures. We argue that this type of analysis should accompany nonlinear multiparameter studies of stationary as well as transient features in network dynamics.Liang QiaoRobert B NachbarIoannis G KevrekidisStanislav Y ShvartsmanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 3, Iss 9, Pp 1819-1826 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Liang Qiao Robert B Nachbar Ioannis G Kevrekidis Stanislav Y Shvartsman Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.
description	Physicochemical models of signaling pathways are characterized by high levels of structural and parametric uncertainty, reflecting both incomplete knowledge about signal transduction and the intrinsic variability of cellular processes. As a result, these models try to predict the dynamics of systems with tens or even hundreds of free parameters. At this level of uncertainty, model analysis should emphasize statistics of systems-level properties, rather than the detailed structure of solutions or boundaries separating different dynamic regimes. Based on the combination of random parameter search and continuation algorithms, we developed a methodology for the statistical analysis of mechanistic signaling models. In applying it to the well-studied MAPK cascade model, we discovered a large region of oscillations and explained their emergence from single-stage bistability. The surprising abundance of strongly nonlinear (oscillatory and bistable) input/output maps revealed by our analysis may be one of the reasons why the MAPK cascade in vivo is embedded in more complex regulatory structures. We argue that this type of analysis should accompany nonlinear multiparameter studies of stationary as well as transient features in network dynamics.
format	article
author	Liang Qiao Robert B Nachbar Ioannis G Kevrekidis Stanislav Y Shvartsman
author_facet	Liang Qiao Robert B Nachbar Ioannis G Kevrekidis Stanislav Y Shvartsman
author_sort	Liang Qiao
title	Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.
title_short	Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.
title_full	Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.
title_fullStr	Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.
title_full_unstemmed	Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.
title_sort	bistability and oscillations in the huang-ferrell model of mapk signaling.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/bfb39b0aeb3444ffa4ca80d07d39c2c3
work_keys_str_mv	AT liangqiao bistabilityandoscillationsinthehuangferrellmodelofmapksignaling AT robertbnachbar bistabilityandoscillationsinthehuangferrellmodelofmapksignaling AT ioannisgkevrekidis bistabilityandoscillationsinthehuangferrellmodelofmapksignaling AT stanislavyshvartsman bistabilityandoscillationsinthehuangferrellmodelofmapksignaling
_version_	1718414541579091968

Bistability and oscillations in the Huang-Ferrell model of MAPK signaling.

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