Discrete time piecewise affine models of genetic regulatory networks

A mathematical model for a two-gene regulatory network is derived and several of their properties analyzed. Due to the presence of mixed continuous/discrete dynamics and hysteresis, we employ a hybrid systems model to capture the dynamics of the system. The proposed model incorporates binary hysteresis with different thresholds capturing the interaction between the genes. We analyze properties of the solutions and asymptotic stability of equilibria in the system as a function...

Modeling gene regulatory networks (GRNs) is an important topic in systems biology. Although there has been much work focusing on various specific systems, the generic behavior of GRNs with continuous variables is still elusive. In particular, it is not clear typically how attractors partition among the three types of orbits: steady state, periodic and chaotic, and how the dynamical properties change with network's topological characteristics. In this work, we first investigat...

The biologist Ren\'e Thomas conjectured, twenty years ago, that the presence of a negative feedback circuit in the interaction graph of a dynamical system is a necessary condition for this system to produce sustained oscillations. In this paper, we state and prove this conjecture for asynchronous automata networks, a class of discrete dynamical systems extensively used to model the behaviors of gene networks. As a corollary, we obtain the following fixed point theorem: given ...

Complex dynamical systems are often modeled as networks, with nodes representing dynamical units which interact through the network's links. Gene regulatory networks, responsible for the production of proteins inside a cell, are an example of system that can be described as a network of interacting genes. The behavior of a complex dynamical system is characterized by cooperativity of its units at various scales, leading to emergent dynamics which is related to the system's fu...

As a model for gene and protein interactions we study a set for molecular catalytic reactions. The model is based on experimentally motivated interaction network topologies, and is designed to capture some key statistics of gene expression statistics. We impose a non-linearity to the system by a boundary condition which guarantees non-negative concentrations of chemical concentrations and study the system stability quantified by maximum Lyapunov exponents. We find that the no...

The structure and dynamics of a typical biological system are complex due to strong and inhomogeneous interactions between its constituents. The investigation of such systems with classical mathematical tools, such as differential equations for their dynamics, is not always suitable. The graph theoretical models may serve as a rough but powerful tool in such cases. In this thesis, I first consider the network modeling for the representation of the biological systems. Both the...

We model intracellular regulatory dynamics with threshold-type state-dependent delay and investigate the effect of the state-dependent diffusion time. A general model which is an extension of the classic differential equation models with constant or zero time delays is developed to study the stability of steady state, the occurrence and stability of periodic oscillations in regulatory dynamics. Using the method of multiple time scales, we compute the normal form of the genera...

We study the dynamical properties of small regulatory networks treated as non autonomous dynamical systems called modules when working inside larger networks or, equivalently when subject to external signal inputs. Particular emphasis is put on the interplay between the internal properties of the open systems and the different possible inputs on them to deduce new functionalities of the modules. We use discrete-time, piecewise-affine and piecewise-contracting models with inte...

Genetic regulatory networks are defined by their topology and by a multitude of continuously adjustable parameters. Here we present a class of simple models within which the relative importance of topology vs. interaction strengths becomes a well-posed problem. We find that complexity - the ability of the network to adopt multiple stable states - is dominated by the adjustable parameters. We comment on the implications for real networks and their evolution.

We study the oscillatory behaviour of a gene regulatory network with interlinked positive and negative feedback loop. Frequency and amplitude are two important properties of oscillation. Studied network produces two different modes of oscillation. In one mode (mode 1) frequency remains constant over a wide range amplitude and in other mode (mode 2) the amplitude of oscillation remains constant over a wide range of frequency. Our study reproduces both features of oscillations ...