Geometric analysis of pathways dynamics: application to versatility of TGF-β receptors - Inria - Institut national de recherche en sciences et technologies du numérique Accéder directement au contenu
Article Dans Une Revue BioSystems Année : 2016

Geometric analysis of pathways dynamics: application to versatility of TGF-β receptors

Résumé

We propose a new geometric approach to describe the qualitative dynamics of chemical reactions networks. By this method we identify metastable regimes, defined as low dimensional regions of the phase space close to which the dynamics is much slower compared to the rest of the phase space. These metastable regimes depend on the network topology and on the orders of magnitude of the kinetic parameters. Benchmarking of the method on a computational biology model repository suggests that the number of metastable regimes is sub-exponential in the number of variables and equations. The dynamics of the network can be described as a sequence of jumps from one metastable regime to another. We show that a geometrically computed con-nectivity graph restricts the set of possible jumps. We also provide finite state machine (Markov chain) models for such dynamic changes. Applied to signal transduction models, our approach unravels dynamical and functional * corresponding author capacities of signalling pathways, as well as parameters responsible for speci-ficity of the pathway response. In particular, for a model of TGFβ signalling, we find that the ratio of TGFBR2 to TGFBR1 receptors concentrations can be used to discriminate between metastable regimes. Using expression data from the NCI60 panel of human tumor cell lines, we show that aggressive and non-aggressive tumour cell lines function in different metastable regimes and can be distinguished by measuring the relative concentrations of receptors of the two types.
Fichier principal
Vignette du fichier
Samal_et_al_Biosystems_final.pdf (756.03 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01379033 , version 1 (11-10-2016)

Identifiants

Citer

Satya Swarup Samal, Aurélien Naldi, Dima Grigoriev, Andreas Weber, Nathalie Théret, et al.. Geometric analysis of pathways dynamics: application to versatility of TGF-β receptors. BioSystems, 2016, 149, pp.3-14. ⟨10.1016/j.biosystems.2016.07.004⟩. ⟨hal-01379033⟩
413 Consultations
174 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More