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Author (up) Ruz, G.A.; Timmermann, T.; Barrera, J.; Goles, E. pdf  doi
  Title Neutral space analysis for a Boolean network model of the fission yeast cell cycle network Type
  Year 2014 Publication Biological Research Abbreviated Journal Biol. Res.  
  Volume 47 Issue Pages 12 pp  
  Keywords Neutral graph; Boolean networks; Evolution strategy; Fission yeast cell cycle; Attractors  
  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 G(1) 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.  
  Address [Ruz, Gonzalo A.; Timmermann, Tania; Barrera, Javiera; Goles, Eric] Univ Adolfo Ibanez, Fac Ingn & Ciencias, Santiago, Chile, Email:  
  Corporate Author Thesis  
  Publisher Soc Biolgia Chile Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0716-9760 ISBN Medium  
  Area Expedition Conference  
  Notes WOS:000348529400004 Approved  
  Call Number UAI @ eduardo.moreno @ Serial 440  
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