May 3, 2005
We introduce simple models of genetic regulatory networks and we proceed to the mathematical analysis of their dynamics. The models are discrete time dynamical systems generated by piecewise affine contracting mappings whose variables represent gene expression levels. When compared to other models of regulatory networks, these models have an additional parameter which is identified as quantifying interaction delays. In spite of their simplicity, their dynamics presents a rich variety of behaviours. This phenomenology is not limited to piecewise affine model but extends to smooth nonlinear discrete time models of regulatory networks. In a first step, our analysis concerns general properties of networks on arbitrary graphs (characterisation of the attractor, symbolic dynamics, Lyapunov stability, structural stability, symmetries, etc). In a second step, focus is made on simple circuits for which the attractor and its changes with parameters are described. In the negative circuit of 2 genes, a thorough study is presented which concern stable (quasi-)periodic oscillations governed by rotations on the unit circle -- with a rotation number depending continuously and monotonically on threshold parameters. These regular oscillations exist in negative circuits with arbitrary number of genes where they are most likely to be observed in genetic systems with non-negligible delay effects.
Similar papers 1
November 8, 2006
In this paper the existence and unicity of a stable periodic orbit is proven, for a class of piecewise affine differential equations in dimension 3 or more, provided their interaction structure is a negative feedback loop. It is also shown that the same systems converge toward a unique stable equilibrium point in dimension 2. This extends a theorem of Snoussi, which showed the existence of these orbits only. The considered class of equations is usually studied as a model of g...
December 2, 2009
Hybrid systems, and especially piecewise affine (PWA) systems, are often used to model gene regulatory networks. In this paper we elaborate on previous work about control problems for this class of models, using also some recent results guaranteeing the existence and uniqueness of limit cycles, based solely on a discrete abstraction of the system and its interaction structure. Our aim is to control the transition graph of the PWA system to obtain an oscillatory behaviour, whi...
December 27, 2012
This paper is concerned with conditions for the existence of oscillations in gene regulatory networks with negative cyclic feedback, where time delays in transcription, translation and translocation process are explicitly considered. The primary goal of this paper is to propose systematic analysis tools that are useful for a broad class of cyclic gene regulatory networks, and to provide novel biological insights. To this end, we adopt a simplified model that is suitable for c...
March 11, 2009
In this paper we consider piecewise affine differential equations modeling gene networks. We work with arbitrary decay rates, and under a local hypothesis expressed as an alignment condition of successive focal points. The interaction graph of the system may be rather complex (multiple intricate loops of any sign, multiple thresholds...). Our main result is an alternative theorem showing that, if a sequence of region is periodically visited by trajectories, then under our hyp...
September 7, 2005
Genetic regulatory networks are usually modeled by systems of coupled differential equations and by finite state models, better known as logical networks, are also used. In this paper we consider a class of models of regulatory networks which present both discrete and continuous aspects. Our models consist of a network of units, whose states are quantified by a continuous real variable. The state of each unit in the network evolves according to a contractive transformation ch...
June 28, 2019
In this work we addressed the problem of stability analysis for an uncertain piecewise affine model of a genetic regulatory network. In particular we considered polytopic parameter uncertainties on the proteins production rate functions, giving conditions for the existence of a piecewise quadratic Lyapunov function for any possible realization of the system. In the spirit of other works in literature, the resulting conditions will be given on the vertices of the parameter pol...
May 7, 2010
Linearized catalytic reaction equations modeling e.g. the dynamics of genetic regulatory networks under the constraint that expression levels, i.e. molecular concentrations of nucleic material are positive, exhibit nontrivial dynamical properties, which depend on the average connectivity of the reaction network. In these systems the inflation of the edge of chaos and multi-stability have been demonstrated to exist. The positivity constraint introduces a nonlinearity which mak...
March 31, 2021
In this paper we investigate equilibria of continuous differential equation models of network dynamics. The motivation comes from gene regulatory networks where each directed edge represents either down- or up-regulation, and is modeled by a sigmoidal nonlinear function. We show that the existence and stability of equilibria of a sigmoidal system is determined by a combinatorial analysis of the limiting switching system with piece-wise constant non-linearities. In addition, w...
October 14, 2005
We consider some mathematical issues raised by the modelling of gene networks. The expression of genes is governed by a complex set of regulations, which is often described symbolically by interaction graphs. Once such a graph has been established, there remains the difficult task to decide which dynamical properties of the gene network can be inferred from it, in the absence of precise quantitative data about their regulation. In this paper we discuss a rule proposed by R.Th...
February 28, 2007
The switch-like character of gene regulation has motivated the use of hybrid, discrete-continuous models of genetic regulatory networks. While powerful techniques for the analysis, verification, and control of hybrid systems have been developed, the specificities of the biological application domain pose a number of challenges, notably the absence of quantitative information on parameter values and the size and complexity of networks of biological interest. We introduce a met...