Emergence of switch-like behavior in a large family of simple biochemical networks.

Bistability plays a central role in the gene regulatory networks (GRNs) controlling many essential biological functions, including cellular differentiation and cell cycle control. However, establishing the network topologies that can exhibit bistability remains a challenge, in part due to the exceed...

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Autores principales:	Dan Siegal-Gaskins, Maria Katherine Mejia-Guerra, Gregory D Smith, Erich Grotewold
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4afa6bc3f26446fc82febb692eee5f02
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spelling	oai:doaj.org-article:4afa6bc3f26446fc82febb692eee5f022021-11-18T05:50:33ZEmergence of switch-like behavior in a large family of simple biochemical networks.1553-734X1553-735810.1371/journal.pcbi.1002039https://doaj.org/article/4afa6bc3f26446fc82febb692eee5f022011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21589886/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Bistability plays a central role in the gene regulatory networks (GRNs) controlling many essential biological functions, including cellular differentiation and cell cycle control. However, establishing the network topologies that can exhibit bistability remains a challenge, in part due to the exceedingly large variety of GRNs that exist for even a small number of components. We begin to address this problem by employing chemical reaction network theory in a comprehensive in silico survey to determine the capacity for bistability of more than 40,000 simple networks that can be formed by two transcription factor-coding genes and their associated proteins (assuming only the most elementary biochemical processes). We find that there exist reaction rate constants leading to bistability in ∼90% of these GRN models, including several circuits that do not contain any of the TF cooperativity commonly associated with bistable systems, and the majority of which could only be identified as bistable through an original subnetwork-based analysis. A topological sorting of the two-gene family of networks based on the presence or absence of biochemical reactions reveals eleven minimal bistable networks (i.e., bistable networks that do not contain within them a smaller bistable subnetwork). The large number of previously unknown bistable network topologies suggests that the capacity for switch-like behavior in GRNs arises with relative ease and is not easily lost through network evolution. To highlight the relevance of the systematic application of CRNT to bistable network identification in real biological systems, we integrated publicly available protein-protein interaction, protein-DNA interaction, and gene expression data from Saccharomyces cerevisiae, and identified several GRNs predicted to behave in a bistable fashion.Dan Siegal-GaskinsMaria Katherine Mejia-GuerraGregory D SmithErich GrotewoldPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 5, p e1002039 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Dan Siegal-Gaskins Maria Katherine Mejia-Guerra Gregory D Smith Erich Grotewold Emergence of switch-like behavior in a large family of simple biochemical networks.
description	Bistability plays a central role in the gene regulatory networks (GRNs) controlling many essential biological functions, including cellular differentiation and cell cycle control. However, establishing the network topologies that can exhibit bistability remains a challenge, in part due to the exceedingly large variety of GRNs that exist for even a small number of components. We begin to address this problem by employing chemical reaction network theory in a comprehensive in silico survey to determine the capacity for bistability of more than 40,000 simple networks that can be formed by two transcription factor-coding genes and their associated proteins (assuming only the most elementary biochemical processes). We find that there exist reaction rate constants leading to bistability in ∼90% of these GRN models, including several circuits that do not contain any of the TF cooperativity commonly associated with bistable systems, and the majority of which could only be identified as bistable through an original subnetwork-based analysis. A topological sorting of the two-gene family of networks based on the presence or absence of biochemical reactions reveals eleven minimal bistable networks (i.e., bistable networks that do not contain within them a smaller bistable subnetwork). The large number of previously unknown bistable network topologies suggests that the capacity for switch-like behavior in GRNs arises with relative ease and is not easily lost through network evolution. To highlight the relevance of the systematic application of CRNT to bistable network identification in real biological systems, we integrated publicly available protein-protein interaction, protein-DNA interaction, and gene expression data from Saccharomyces cerevisiae, and identified several GRNs predicted to behave in a bistable fashion.
format	article
author	Dan Siegal-Gaskins Maria Katherine Mejia-Guerra Gregory D Smith Erich Grotewold
author_facet	Dan Siegal-Gaskins Maria Katherine Mejia-Guerra Gregory D Smith Erich Grotewold
author_sort	Dan Siegal-Gaskins
title	Emergence of switch-like behavior in a large family of simple biochemical networks.
title_short	Emergence of switch-like behavior in a large family of simple biochemical networks.
title_full	Emergence of switch-like behavior in a large family of simple biochemical networks.
title_fullStr	Emergence of switch-like behavior in a large family of simple biochemical networks.
title_full_unstemmed	Emergence of switch-like behavior in a large family of simple biochemical networks.
title_sort	emergence of switch-like behavior in a large family of simple biochemical networks.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/4afa6bc3f26446fc82febb692eee5f02
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Emergence of switch-like behavior in a large family of simple biochemical networks.

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