Neutral space analysis for a Boolean network model of the fission yeast cell cycle network

BACKGROUND: Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gen...

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Autores principales:	Ruz,Gonzalo A, Timmermann,Tania, Barrera,Javiera, Goles,Eric
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2014
Materias:	Neutral graph Boolean networks Evolution strategy Fission yeast cell cycle Attractors
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100058
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spelling	oai:scielo:S0716-976020140001000582015-10-30Neutral space analysis for a Boolean network model of the fission yeast cell cycle networkRuz,Gonzalo ATimmermann,TaniaBarrera,JavieraGoles,Eric Neutral graph Boolean networks Evolution strategy Fission yeast cell cycle Attractors BACKGROUND: Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle. RESULTS: Through simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G1 fixed point was found for deterministic updating schemes. CONCLUSIONS: In general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.47 20142014-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100058en10.1186/0717-6287-47-64
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Neutral graph Boolean networks Evolution strategy Fission yeast cell cycle Attractors
spellingShingle	Neutral graph Boolean networks Evolution strategy Fission yeast cell cycle Attractors Ruz,Gonzalo A Timmermann,Tania Barrera,Javiera Goles,Eric Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
description	BACKGROUND: Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle. RESULTS: Through simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G1 fixed point was found for deterministic updating schemes. CONCLUSIONS: In general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component.
author	Ruz,Gonzalo A Timmermann,Tania Barrera,Javiera Goles,Eric
author_facet	Ruz,Gonzalo A Timmermann,Tania Barrera,Javiera Goles,Eric
author_sort	Ruz,Gonzalo A
title	Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
title_short	Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
title_full	Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
title_fullStr	Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
title_full_unstemmed	Neutral space analysis for a Boolean network model of the fission yeast cell cycle network
title_sort	neutral space analysis for a boolean network model of the fission yeast cell cycle network
publisher	Sociedad de Biología de Chile
publishDate	2014
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100058
work_keys_str_mv	AT ruzgonzaloa neutralspaceanalysisforabooleannetworkmodelofthefissionyeastcellcyclenetwork AT timmermanntania neutralspaceanalysisforabooleannetworkmodelofthefissionyeastcellcyclenetwork AT barrerajaviera neutralspaceanalysisforabooleannetworkmodelofthefissionyeastcellcyclenetwork AT goleseric neutralspaceanalysisforabooleannetworkmodelofthefissionyeastcellcyclenetwork
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Neutral space analysis for a Boolean network model of the fission yeast cell cycle network

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