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Retroactivity as a Criterion to Define Modules in Signaling Networks

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Design and Analysis of Biomolecular Circuits

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Abstract

The concept of modularity has been widely studied in the context of molecular biology. Since engineering sciences are used to work in a modular manner, it is tempting to approach the definition of biological modules from an engineering perspective. From a system-theoretical point of view an interesting criterion might be the definition of modules where both the input signals and the output signals are unidirectional, that is, there is no retroactivity. In this chapter, we review the applicability of this concept to biological networks. We start describing which biochemical situations can lead to absence of retroactivity. Then, we show how this concept can be automatized into an algorithm to decompose biochemical networks into modules so that the retroactivity among the modules is minimized. This decomposition facilitates the analysis of complex models because the modules can, to some degree, be studied separately. We complement this analysis with a consideration of retroactivity in signal transduction processes using a domain-oriented description. Finally, we explore the interplay between retroactivity and thermodynamics in the domain-oriented description, and show how the binding site phosphorylation is a mechanism that is able to realize unidirectional signal transduction.

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Notes

  1. 1.

    We coined the term retroactivity in [22, 23] as a translation of the German word Rückwirkung, that can be more accurately translated by the longer expression ‘backwards effect’.

  2. 2.

    This section summarizes the work described in [23, 24]. Some portions of the text and figures are reproduced, with permission from Elsevier and Oxford University Press, respectively.

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Acknowledgments

We thank Eduardo Sontag for useful discussions. The work described here was supported by DFG (FOR521) and the German Ministry of Research and Education BMBF (SysTec Initative, HepatoSys, DYNAMO Consortium).

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Authors and Affiliations

  1. Genome Biology Unit, European Bioinformatics Institute (EMBL-EBI) and EMBL-Heidelberg, Wellcome Trust Genome Campus, Cambridge, CB10 1SD, UK

    Julio Saez-Rodriguez

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  1. Julio Saez-Rodriguez
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  2. Holger Conzelmann
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  3. Michael Ederer
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  4. Ernst Dieter Gilles
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Corresponding author

Correspondence to Julio Saez-Rodriguez .

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Editors and Affiliations

  1. , Automatic Control Laboratory, ETH Zurich, Physikstrasse 3, Zurich, 8092, Switzerland

    Heinz Koeppl

  2. ARCES, Università di Bologna, Via Toffano 2/2, Bologna, 40125, Italy

    Gianluca Setti

  3. Università di Napoli Federico II, Via Claudio 21, Napoli, 80125, Italy

    Mario di Bernardo

  4. , Department of Electrical and Computer En, Boston University, Saint Mary's St. 8, Boston, 02446, Massachusetts, USA

    Douglas Densmore

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Saez-Rodriguez, J., Conzelmann, H., Ederer, M., Gilles, E.D. (2011). Retroactivity as a Criterion to Define Modules in Signaling Networks. In: Koeppl, H., Setti, G., di Bernardo, M., Densmore, D. (eds) Design and Analysis of Biomolecular Circuits. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6766-4_7

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  • DOI: https://doi.org/10.1007/978-1-4419-6766-4_7

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