Synchronization of stochastic genetic oscillator networks with time delays and Markovian jumping parameters

The official published version of the article can be found at the link below.Genetic oscillator networks (GONs) are inherently coupled complex systems where the nodes indicate the biochemicals and the couplings represent the biochemical interactions. This paper is concerned with the synchronization problem of a general class of stochastic GONs with time delays and Markovian jumping parameters, where the GONs are subject to both the stochastic disturbances and the Markovian parameter switching. The regulatory functions of the addressed GONs are described by the sector-like nonlinear functions. By applying up-to-date ‘delay-fractioning’ approach for achieving delay-dependent conditions, we construct novel matrix functional to derive the synchronization criteria for the GONs that are formulated in terms of linear matrix inequalities (LMIs). Note that LMIs are easily solvable by the Matlab toolbox. A simulation example is used to demonstrate the synchronization phenomena within biological organisms of a given GON and therefore shows the applicability of the obtained results.This work was supported in part by the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK under Grants BB/C506264/1 and 100/EGM17735, the Royal Society of the UK, the National Natural Science Foundation of China under Grant 60804028, the Teaching and Research Fund for Excellent Young Teachers at Southeast University of China, the International Science and Technology Cooperation Project of China under Grant 2009DFA32050, and the Alexander von Humboldt Foundation of Germany

Boolean Delay Equations: A simple way of looking at complex systems

Boolean Delay Equations (BDEs) are semi-discrete dynamical models with Boolean-valued variables that evolve in continuous time. Systems of BDEs can be classified into conservative or dissipative, in a manner that parallels the classification of ordinary or partial differential equations. Solutions to certain conservative BDEs exhibit growth of complexity in time. They represent therewith metaphors for biological evolution or human history. Dissipative BDEs are structurally stable and exhibit multiple equilibria and limit cycles, as well as more complex, fractal solution sets, such as Devil's staircases and ``fractal sunbursts``. All known solutions of dissipative BDEs have stationary variance. BDE systems of this type, both free and forced, have been used as highly idealized models of climate change on interannual, interdecadal and paleoclimatic time scales. BDEs are also being used as flexible, highly efficient models of colliding cascades in earthquake modeling and prediction, as well as in genetics. In this paper we review the theory of systems of BDEs and illustrate their applications to climatic and solid earth problems. The former have used small systems of BDEs, while the latter have used large networks of BDEs. We moreover introduce BDEs with an infinite number of variables distributed in space (``partial BDEs``) and discuss connections with other types of dynamical systems, including cellular automata and Boolean networks. This research-and-review paper concludes with a set of open questions.Comment: Latex, 67 pages with 15 eps figures. Revised version, in particular the discussion on partial BDEs is updated and enlarge

Oscillations and temporal signalling in cells

The development of new techniques to quantitatively measure gene expression in cells has shed light on a number of systems that display oscillations in protein concentration. Here we review the different mechanisms which can produce oscillations in gene expression or protein concentration, using a framework of simple mathematical models. We focus on three eukaryotic genetic regulatory networks which show "ultradian" oscillations, with time period of the order of hours, and involve, respectively, proteins important for development (Hes1), apoptosis (p53) and immune response (NFkB). We argue that underlying all three is a common design consisting of a negative feedback loop with time delay which is responsible for the oscillatory behaviour

Time-delayed models of gene regulatory networks

We discuss different mathematical models of gene regulatory networks as relevant to the onset and development of cancer. After discussion of alternativemodelling 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 some open problems

Oscillatory regulation of Hes1: discrete stochastic delay modelling and simulation

Discrete stochastic simulations are a powerful tool for understanding the dynamics of chemical kinetics when there are small-to-moderate numbers of certain molecular species. In this paper we introduce delays into the stochastic simulation algorithm, thus mimicking delays associated with transcription and translation. We then show that this process may well explain more faithfully than continuous deterministic models the observed sustained oscillations in expression levels of hes1 mRNA and Hes1 protein

Robust H∞ feedback control for uncertain stochastic delayed genetic regulatory networks with additive and multiplicative noise

The official published version can found at the link below.Noises are ubiquitous in genetic regulatory networks (GRNs). Gene regulation is inherently a stochastic process because of intrinsic and extrinsic noises that cause kinetic parameter variations and basal rate disturbance. Time delays are usually inevitable due to different biochemical reactions in such GRNs. In this paper, a delayed stochastic model with additive and multiplicative noises is utilized to describe stochastic GRNs. A feedback gene controller design scheme is proposed to guarantee that the GRN is mean-square asymptotically stable with noise attenuation, where the structure of the controllers can be specified according to engineering requirements. By applying control theory and mathematical tools, the analytical solution to the control design problem is given, which helps to provide some insight into synthetic biology and systems biology. The control scheme is employed in a three-gene network to illustrate the applicability and usefulness of the design.This work was funded by Royal Society of the U.K.; Foundation for the Author of National Excellent Doctoral Dissertation of China. Grant Number: 2007E4; Heilongjiang Outstanding Youth Science Fund of China. Grant Number: JC200809; Fok Ying Tung Education Foundation. Grant Number: 111064; International Science and Technology Cooperation Project of China. Grant Number: 2009DFA32050; University of Science and Technology of China Graduate Innovative Foundation

Synchronization of Coupled Nonidentical Genetic Oscillators

The study on the collective dynamics of synchronization among genetic oscillators is essential for the understanding of the rhythmic phenomena of living organisms at both molecular and cellular levels. Genetic oscillators are biochemical networks, which can generally be modelled as nonlinear dynamic systems. We show in this paper that many genetic oscillators can be transformed into Lur'e form by exploiting the special structure of biological systems. By using control theory approach, we provide a theoretical method for analyzing the synchronization of coupled nonidentical genetic oscillators. Sufficient conditions for the synchronization as well as the estimation of the bound of the synchronization error are also obtained. To demonstrate the effectiveness of our theoretical results, a population of genetic oscillators based on the Goodwin model are adopted as numerical examples.Comment: 16 pages, 3 figure