Reduction of a stochastic hybrid model of gene expression using Large deviations theory

Date/heure
10 juin 2021
10:45 - 11:45

Lieu
Teams

Oratrice ou orateur
Elias Ventre (LBMC, ENS Lyon)

Catégorie d'évènement
Séminaire Probabilités et Statistique


Résumé

Differentiation is the process whereby a cell acquires a specific phenotype, by differential gene expression as a function of time. This is thought to result from the dynamical functioning of an underlying Gene Regulatory Network (GRN). The precise path from the stochastic GRN behavior to the resulting cell state is still an open question. In this presentation, we detail a methodology to reduce a mechanistic model characterizing the evolution of a cell by a system of piecewise deterministic Markov processes (PDMP), to a discrete coarse-grained model on a limited number of cell types, defined as the basins of attraction of the deterministic limit. The transitions between the basins in the weak noise limit can be determined by the unique solution of an Hamilton-Jacobi equation under a particular constraint, which corresponds to the rate function associated to a Large Deviations Principle for the PDMP. We develop a numerical method for approximating the coarse-grained model parameters, and show its accuracy for a toggle-switch network. We deduce from the reduced model an analytical approximation of the stationary distribution of the PDMP system, which appears as a Beta mixture.