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Yeast Systems Biology pp 365–385Cite as

Advanced Modeling of Cellular Proliferation: Toward a Multi-scale Framework Coupling Cell Cycle to Metabolism by Integrating Logical and Constraint-Based Models

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2049))

Abstract

Biological functions require a coherent cross talk among multiple layers of regulation within the cell. Computational efforts that aim to understand how these layers are integrated across spatial, temporal, and functional scales represent a challenge in Systems Biology. We have developed a computational, multi-scale framework that couples cell cycle and metabolism networks in the budding yeast cell. Here we describe the methodology at the basis of this framework, which integrates on off-the-shelf logical (Boolean) models of a minimal yeast cell cycle with a constraint-based model of metabolism (i.e., the Yeast 7 metabolic network reconstruction). Models are implemented in Python code using the BooleanNet and COBRApy packages, respectively, and are connected through the Boolean logic. The methodology allows for incorporation of interaction data, and validation through –omics data. Furthermore, evolutionary strategies may be incorporated to explore regulatory structures underlying coherent cross talks among regulatory layers.

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Acknowledgments

This work was supported by the Systems Biology Grant of the University of Surrey to M.B., and by the SILS Starting Grant of the University of Amsterdam (UvA) and by the UvA-Systems Biology Research Priority Area Grant to M.B.

Author contribution: M.B. conceived the idea and designed the study. L.v.d.Z. and M.B. designed the computational analyses. L.v.d.Z. programmed the source code and performed the simulations. L.v.d.Z. and M.B. analyzed the data. L.v.d.Z. and M.B. wrote the chapter. M.B. provided scientific leadership and supervised the study.

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Authors and Affiliations

  1. Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

    Lucas van der Zee & Matteo Barberis

  2. Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

    Lucas van der Zee & Matteo Barberis

Authors
  1. Lucas van der Zee
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  2. Matteo Barberis
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Corresponding author

Correspondence to Matteo Barberis .

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Editors and Affiliations

  1. Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK

    Stephen G. Oliver

  2. Genetadi Biotech, Parque Tecnológico de Bizkaia, Biscay, Spain

    Juan I. Castrillo

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van der Zee, L., Barberis, M. (2019). Advanced Modeling of Cellular Proliferation: Toward a Multi-scale Framework Coupling Cell Cycle to Metabolism by Integrating Logical and Constraint-Based Models. In: Oliver, S.G., Castrillo, J.I. (eds) Yeast Systems Biology. Methods in Molecular Biology, vol 2049. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9736-7_21

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  • DOI: https://doi.org/10.1007/978-1-4939-9736-7_21

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9735-0

  • Online ISBN: 978-1-4939-9736-7

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