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

Ruz, Gonzalo A.; Timmermann, Tania; Barrera, Javiera; Goles, Eric

Authors

Gonzalo A. Ruz

Tania Timmermann

Javiera Barrera

Eric Goles



Abstract

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.

Journal Article Type Article
Acceptance Date Nov 13, 2014
Publication Date Nov 25, 2014
Deposit Date Mar 5, 2020
Publicly Available Date Mar 5, 2020
Journal Biological Research
Electronic ISSN 0717-6287
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 47
Issue 1
DOI https://doi.org/10.1186/0717-6287-47-64
Public URL https://uwe-repository.worktribe.com/output/5608228

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Neutral space analysis for a Boolean network model of the fission yeast cell cycle network (2.3 Mb)
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http://creativecommons.org/licenses/by/4.0/

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Copyright 2014 Ruz et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.





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