Formulas for intrinsic noise evaluation in oscillatory genetic networks

The linear noise approximation is a useful method for stochastic noise evaluations in genetic regulatory networks, where the covariance equation described as a Lyapunov equation plays a central role. We discuss the linear noise approximation method for evaluations of an intrinsic noise in autonomously oscillatory genetic networks; in such oscillatory networks, the covariance equation becomes a periodic differential equation that provides generally an unbounded covariance matrix, so that the standard method of noise evaluation based on the covariance matrix cannot be adopted directly. In this paper, we develop a new method of noise evaluation in oscillatory genetic networks; first, we investigate structural properties, e.g., orbital stability and periodicity, of the solutions to the covariance equation given as a periodic Lyapunov differential equation by using the Floquet-Lyapunov theory, and propose a global measure for evaluating stochastic amplitude fluctuations on the periodic trajectory; we also derive an evaluation formula for the period fluctuation. Finally, we apply our method to a model of circadian oscillations based on negative auto-regulation of gene expression, and show validity of our method by comparing the evaluation results with stochastic simulations.     

Global robust power-rate stability of delayed genetic regulatory networks with noise perturbations

In this paper, by using the Lyapunov method, Itô’s differential formula and linear matrix inequality (LMI) approach, the global robust power-rate stability in mean square is discussed for genetic regulatory networks with unbounded time-varying delay, noise perturbations and parameter uncertainties. Sufficient conditions are given to ensure the robust power-rate stability (in mean square) of the genetic regulatory networks. Meanwhile, the criteria ensuring global power-rate stability in mean square are a byproduct of the criteria guaranteeing global robust power-rate stability in mean square. The obtained conditions are derived in terms of linear matrix inequalities (LMIs) which are easy to be verified via the LMI toolbox. An illustrative example is given to show the effectiveness of the obtained result.     

On multistability of delayed genetic regulatory networks with multivariable regulation functions

Many genetic regulatory networks (GRNs) have the capacity to reach different stable states. This capacity is defined as multistability which is an important regulation mechanism. Multiple time delays and multivariable regulation functions are usually inevitable in such GRNs. In this paper, multistability of GRNs is analyzed by applying the control theory and mathematical tools. This study is to provide a theoretical tool to facilitate the design of synthetic gene circuit with multistability in the perspective of control theory. By transforming such GRNs into a new and uniform mathematical formulation, we put forward a general sector-like regulation function that is capable of quantifying the regulation effects in a more precise way. By resorting to up-to-date techniques, a novel Lyapunov-Krasovskii functional (LKF) is introduced for achieving delay dependence to ensure less conservatism. New conditions are then proposed to ensure the multistability of a GRN in the form of linear matrix inequalities (LMIs) that are dependent on the delays. Our multistability conditions are applicable to several frequently used regulation functions especially the multivariable ones. Two examples are employed to illustrate the applicability and usefulness of the developed theoretical results.     

Unconditional global exponential stability in Lagrange sense of genetic regulatory networks with SUM regulatory logic

In this paper, the global exponential stability in Lagrange sense for genetic regulatory networks (GRNs) with SUM regulatory logic is firstly studied. By constructing appropriate Lyapunov-like functions, several criteria are presented for the boundedness, ultimate boundedness and global exponential attractivity of GRNs. It can be obtained that GRNs with SUM regulatory logic are unconditionally globally exponentially stable in Lagrange sense. These results can be applied to analyze monostable as well as multistable networks. Furthermore, to analyze the stability for GRNs more comprehensively, the existence of equilibrium point of GRNs is proved, and some sufficient conditions of the global exponential stability in Lyapunov sense for GRNs are derived. Finally two numerical examples are given to illustrate the application of the obtained results.