7,469 research outputs found
A finite state projection algorithm for the stationary solution of the chemical master equation
The chemical master equation (CME) is frequently used in systems biology to
quantify the effects of stochastic fluctuations that arise due to biomolecular
species with low copy numbers. The CME is a system of ordinary differential
equations that describes the evolution of probability density for each
population vector in the state-space of the stochastic reaction dynamics. For
many examples of interest, this state-space is infinite, making it difficult to
obtain exact solutions of the CME. To deal with this problem, the Finite State
Projection (FSP) algorithm was developed by Munsky and Khammash (Jour. Chem.
Phys. 2006), to provide approximate solutions to the CME by truncating the
state-space. The FSP works well for finite time-periods but it cannot be used
for estimating the stationary solutions of CMEs, which are often of interest in
systems biology. The aim of this paper is to develop a version of FSP which we
refer to as the stationary FSP (sFSP) that allows one to obtain accurate
approximations of the stationary solutions of a CME by solving a finite
linear-algebraic system that yields the stationary distribution of a
continuous-time Markov chain over the truncated state-space. We derive bounds
for the approximation error incurred by sFSP and we establish that under
certain stability conditions, these errors can be made arbitrarily small by
appropriately expanding the truncated state-space. We provide several examples
to illustrate our sFSP method and demonstrate its efficiency in estimating the
stationary distributions. In particular, we show that using a quantised tensor
train (QTT) implementation of our sFSP method, problems admitting more than 100
million states can be efficiently solved.Comment: 8 figure
A finite state projection algorithm for the stationary solution of the chemical master equation
The chemical master equation (CME) is frequently used in systems biology to
quantify the effects of stochastic fluctuations that arise due to biomolecular
species with low copy numbers. The CME is a system of ordinary differential
equations that describes the evolution of probability density for each
population vector in the state-space of the stochastic reaction dynamics. For
many examples of interest, this state-space is infinite, making it difficult to
obtain exact solutions of the CME. To deal with this problem, the Finite State
Projection (FSP) algorithm was developed by Munsky and Khammash (Jour. Chem.
Phys. 2006), to provide approximate solutions to the CME by truncating the
state-space. The FSP works well for finite time-periods but it cannot be used
for estimating the stationary solutions of CMEs, which are often of interest in
systems biology. The aim of this paper is to develop a version of FSP which we
refer to as the stationary FSP (sFSP) that allows one to obtain accurate
approximations of the stationary solutions of a CME by solving a finite
linear-algebraic system that yields the stationary distribution of a
continuous-time Markov chain over the truncated state-space. We derive bounds
for the approximation error incurred by sFSP and we establish that under
certain stability conditions, these errors can be made arbitrarily small by
appropriately expanding the truncated state-space. We provide several examples
to illustrate our sFSP method and demonstrate its efficiency in estimating the
stationary distributions. In particular, we show that using a quantised tensor
train (QTT) implementation of our sFSP method, problems admitting more than 100
million states can be efficiently solved.Comment: 8 figure
Context in Synthetic Biology: Memory Effects of Environments with Mono-molecular Reactions
Synthetic biology aims at designing modular genetic circuits that can be
assembled according to the desired function. When embedded in a cell, a circuit
module becomes a small subnetwork within a larger environmental network, and
its dynamics is therefore affected by potentially unknown interactions with the
environment. It is well-known that the presence of the environment not only
causes extrinsic noise but also memory effects, which means that the dynamics
of the subnetwork is affected by its past states via a memory function that is
characteristic of the environment. We study several generic scenarios for the
coupling between a small module and a larger environment, with the environment
consisting of a chain of mono-molecular reactions. By mapping the dynamics of
this coupled system onto random walks, we are able to give exact analytical
expressions for the arising memory functions. Hence, our results give insights
into the possible types of memory functions and thereby help to better predict
subnetwork dynamics.Comment: 14 pages, 6 figures Accepted Versio
Metastability in a stochastic neural network modeled as a velocity jump Markov process
One of the major challenges in neuroscience is to determine how noise that is
present at the molecular and cellular levels affects dynamics and information
processing at the macroscopic level of synaptically coupled neuronal
populations. Often noise is incorprated into deterministic network models using
extrinsic noise sources. An alternative approach is to assume that noise arises
intrinsically as a collective population effect, which has led to a master
equation formulation of stochastic neural networks. In this paper we extend the
master equation formulation by introducing a stochastic model of neural
population dynamics in the form of a velocity jump Markov process. The latter
has the advantage of keeping track of synaptic processing as well as spiking
activity, and reduces to the neural master equation in a particular limit. The
population synaptic variables evolve according to piecewise deterministic
dynamics, which depends on population spiking activity. The latter is
characterised by a set of discrete stochastic variables evolving according to a
jump Markov process, with transition rates that depend on the synaptic
variables. We consider the particular problem of rare transitions between
metastable states of a network operating in a bistable regime in the
deterministic limit. Assuming that the synaptic dynamics is much slower than
the transitions between discrete spiking states, we use a WKB approximation and
singular perturbation theory to determine the mean first passage time to cross
the separatrix between the two metastable states. Such an analysis can also be
applied to other velocity jump Markov processes, including stochastic
voltage-gated ion channels and stochastic gene networks
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