Stochastic Representations of Ion Channel Kinetics and Exact Stochastic Simulation of Neuronal Dynamics

In this paper we provide two representations for stochastic ion channel kinetics, and compare the performance of exact simulation with a commonly used numerical approximation strategy. The first representation we present is a random time change representation, popularized by Thomas Kurtz, with the second being analogous to a "Gillespie" representation. Exact stochastic algorithms are provided for the different representations, which are preferable to either (a) fixed time step or (b) piecewise constant propensity algorithms, which still appear in the literature. As examples, we provide versions of the exact algorithms for the Morris-Lecar conductance based model, and detail the error induced, both in a weak and a strong sense, by the use of approximate algorithms on this model. We include ready-to-use implementations of the random time change algorithm in both XPP and Matlab. Finally, through the consideration of parametric sensitivity analysis, we show how the representations presented here are useful in the development of further computational methods. The general representations and simulation strategies provided here are known in other parts of the sciences, but less so in the present setting.Comment: 39 pages, 6 figures, appendix with XPP and Matlab cod

p-Safe analysis of stochastic hybrid processes

We develop a method for determining whether a stochastic system is safe, i.e., whether its trajectories reach unsafe states. Specifically, we define and solve a probabilistic safety problem for Markov processes. Based on the knowledge of the extended generator, we are able to develop an evolution equation, as a system of integral equations, describing the connection between unsafe and initial states. Subsequently, using the moment method, we approximate the infinite-dimensional optimization problem searching for the largest set of safe states by a finite-dimensional polynomial optimization problem. In particular, we address the above safety problem to a special class of stochastic hybrid processes, namely piecewise-deterministic Markov processes. These are characterized by deterministic dynamics and stochastic jumps, where both the time and the destination of the jumps are stochastic. In addition, the jumps can be both spontaneous (in the style of a Poisson process) and forced (governed by guards). In this case, the extended generator of this process and its corresponding martingale problem turn out to be defined on a rather restricted domain. To circumvent this difficulty, we bring the generalized differential formula of this process into the evolution equation and, subsequently, formulate a polynomial optimization

Piecewise deterministic Markov processes in biological models

We present a short introduction into the framework of piecewise deterministic Markov processes. We illustrate the abstract mathematical setting with a series of examples related to dispersal of biological systems, cell cycle models, gene expression, physiologically structured populations, as well as neural activity. General results concerning asymptotic properties of stochastic semigroups induced by such Markov processes are applied to specific examples.Comment: in: Semigroup of Operators - Theory and Applications, J. Banasiak et al. (eds.), Springer Proceedings in Mathematics & Statistics 113, (2015), pp. 235-25

Adiabatic reduction of models of stochastic gene expression with bursting

This paper considers adiabatic reduction in both discrete and continuous models of stochastic gene expression. In gene expression models, the concept of bursting is a production of several molecules simultaneously and is generally represented as a compound Poisson process of random size. In a general two-dimensional birth and death discrete model, we prove that under specific assumptions and scaling (that are characteristics of the mRNA-protein system) an adiabatic reduction leads to a one-dimensional discrete-state space model with bursting production. The burst term appears through the reduction of the first variable. In a two-dimensional continuous model, we also prove that an adiabatic reduction can be performed in a stochastic slow/fast system. In this gene expression model, the production of mRNA (the fast variable) is assumed to be bursty and the production of protein (the slow variable) is linear as a function of mRNA. When the dynamics of mRNA is assumed to be faster than the protein dynamics (due to a mRNA degradation rate larger than for the protein) we prove that, with the appropriate scaling, the bursting phenomena can be transmitted to the slow variable. We show that the reduced equation is either a stochastic differential equation with a jump Markov process or a deterministic ordinary differential equation depending on the scaling that is appropriate. These results are significant because adiabatic reduction techniques seem to have not been applied to a stochastic differential system containing a jump Markov process. Last but not least, for our particular system, the adiabatic reduction allows us to understand what are the necessary conditions for the bursting production-like of protein to occur.Comment: 24 page