Robustness analysis and behavior discrimination in enzymatic reaction networks
| Autor: | Lucie M. Gattepaille, Eric Fanchon, Oded Maler, Philippe Tracqui, Alexandre Donzé |
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| Přispěvatelé: | VERIMAG (VERIMAG - IMAG), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Grenoble (INPG)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Dynamique Cellulaire et Tissulaire- Interdisciplinarité, Modèles & Microscopies (TIMC-IMAG-DyCTiM) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Boundary detection
Time Factors [SDV]Life Sciences [q-bio] Monte Carlo method lcsh:Medicine Model parameters Parameter space Bioinformatics Biochemistry MESH: Matrix Metalloproteinase 14 0302 clinical medicine Biochemical Simulations lcsh:Science MESH: Oscillometry Bifurcation 0303 health sciences Numerical Analysis Multidisciplinary Calculus Systems Biology Enzymes MESH: Systems Biology Matrix Metalloproteinase 2 Biological system Monte Carlo Method Algorithms Research Article Differential equation MESH: Cell Physiological Phenomena Systems biology High Level Languages MESH: Enzymes MESH: Algorithms MESH: Monte Carlo Method Models Biological Cell Physiological Phenomena 03 medical and health sciences Fuzzy Logic Oscillometry Differential Equations Matrix Metalloproteinase 14 Temporal logic Biology 030304 developmental biology Tissue Inhibitor of Metalloproteinase-2 Models Statistical MESH: Biochemistry lcsh:R MESH: Time Factors MESH: Models Biological Computational Biology Computing Methods MESH: Matrix Metalloproteinase 2 MESH: Tissue Inhibitor of Metalloproteinase-2 Nonlinear Dynamics Computer Science lcsh:Q Programming Languages 030217 neurology & neurosurgery Mathematics MESH: Models Statistical |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2011, 6 (9), pp.e24246. ⟨10.1371/journal.pone.0024246⟩ PLoS ONE, Vol 6, Iss 9, p e24246 (2011) |
| ISSN: | 1932-6203 |
| Popis: | International audience; Characterizing the behavior and robustness of enzymatic networks with numerous variables and unknown parameter values is a major challenge in biology, especially when some enzymes have counter-intuitive properties or switch-like behavior between activation and inhibition. In this paper, we propose new methodological and tool-supported contributions, based on the intuitive formalism of temporal logic, to express in a rigorous manner arbitrarily complex dynamical properties. Our multi-step analysis allows efficient sampling of the parameter space in order to define feasible regions in which the model exhibits imposed or experimentally observed behaviors. In a first step, an algorithmic methodology involving sensitivity analysis is conducted to determine bifurcation thresholds for a limited number of model parameters or initial conditions. In a second step, this boundary detection is supplemented by a global robustness analysis, based on quasi-Monte Carlo approach that takes into account all model parameters. We apply this method to a well-documented enzymatic reaction network describing collagen proteolysis by matrix metalloproteinase MMP2 and membrane type 1 metalloproteinase (MT1-MMP) in the presence of tissue inhibitor of metalloproteinase TIMP2. For this model, our method provides an extended analysis and quantification of network robustness toward paradoxical TIMP2 switching activity between activation or inhibition of MMP2 production. Further implication of our approach is illustrated by demonstrating and analyzing the possible existence of oscillatory behaviors when considering an extended open configuration of the enzymatic network. Notably, we construct bifurcation diagrams that specify key parameters values controlling the co-existence of stable steady and non-steady oscillatory proteolytic dynamics. |
| Databáze: | OpenAIRE |
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