Discrete time piecewise affine models of genetic regulatory networks

In this paper, a novel computational technique for finite discrete approximation of continuous dynamical systems suitable for a significant class of biochemical dynamical systems is introduced. The method is parameterized in order to affect the imposed level of approximation provided that with increasing parameter value the approximation converges to the original continuous system. By employing this approximation technique, we present algorithms solving the reachability probl...

This paper (parts I and II) provides an expository introduction to monotone and near-monotone dynamical systems associated to biochemical networks, those whose graphs are consistent or near-consistent. Many conclusions can be drawn from signed network structure, associated to purely stoichiometric information and ignoring fluxes. In particular, monotone systems respond in a predictable fashion to perturbations and have robust and ordered dynamical characteristics, making them...

A great part of the effort in the study of coarse grained models of transcription networks is directed to the analysis of their dynamical features. In this letter, we consider the \emph{equilibrium} properties of such systems, showing that the logic backbone underlying all dynamic descriptions has the structure of a computational optimization problem. It involves variables, which correspond to gene expression levels, and constraints, which describe the effect of \emph{cis-}re...

This work gives a mathematical foundation for bifurcation from a stable equilibrium in the genome. We construct idealized dynamics associated with the genome. For this dynamics we investigate the two main bifurcations from a stable equilibrium. Finally, we give a mathematical framework for the Repressilator and the Toggle gene circuits.

We consider biochemical systems associated with a generalised class of Petri nets with possibly negative token numbers. We show that the existence of a structural polyhedral Lyapunov function for the biochemical system is equivalent to the boundedness of the associated Petri net evolution or, equivalently, to the finiteness of the number of states reachable from each initial condition. For networks that do not admit a polyhedral Lyapunov function, we investigate whether it is...

In this paper a novel computational technique for finite discrete approximation of continuous dynamical systems suitable for a significant class of biochemical dynamical systems is introduced. The method is parameterized in order to affect the imposed level of approximation provided that with increasing parameter value the approximation converges to the original continuous system. By employing this approximation technique, we present algorithms solving the reachability proble...

In this review we discuss different mathematical models of gene regulatory networks as relevant to the onset and development of cancer. After discussion of alternative modelling approaches, we use a paradigmatic two-gene network to focus on the role played by time delays in the dynamics of gene regulatory networks. We contrast the dynamics of the reduced model arising in the limit of fast mRNA dynamics with that of the full model. The review concludes with the discussion of s...

We consider two mathematical dynamical models of gene regulatory networks (GRNs) and obtain results on robust synchronization on these dynamical models based on the existing theoretical results in the coupled cell network formalism. We also explore the concepts of quotient networks and network lifting in the context of GRNs which are related to the process of gene duplication and the phenomenon of genetic redundancy.

In this review, we give an introduction to the structural and functional properties of the biological networks. We focus on three major themes: topology of complex biological networks like the metabolic and protein-protein interaction networks, nonlinear dynamics in gene regulatory networks and in particular the design of synthetic genetic networks using the concepts and techniques of nonlinear physics and lastly the effect of stochasticity on the dynamics. The examples chose...

In 2000, Elowitz and Leibler introduced the repressilator--a synthetic gene circuit with three genes that cyclically repress transcription of the next gene--as well as a corresponding mathematical model. Experimental data and model simulations exhibited oscillations in the protein concentrations across generations. In 2006, M\"{u}ller \textit{et al.}\ generalized the model to an arbitrary number of genes and analyzed the resulting dynamics. Their new model arose from five key...