19,652 research outputs found
Simulation of stochastic reaction-diffusion processes on unstructured meshes
Stochastic chemical systems with diffusion are modeled with a
reaction-diffusion master equation. On a macroscopic level, the governing
equation is a reaction-diffusion equation for the averages of the chemical
species. On a mesoscopic level, the master equation for a well stirred chemical
system is combined with Brownian motion in space to obtain the
reaction-diffusion master equation. The space is covered by an unstructured
mesh and the diffusion coefficients on the mesoscale are obtained from a finite
element discretization of the Laplace operator on the macroscale. The resulting
method is a flexible hybrid algorithm in that the diffusion can be handled
either on the meso- or on the macroscale level. The accuracy and the efficiency
of the method are illustrated in three numerical examples inspired by molecular
biology
The interplay between discrete noise and nonlinear chemical kinetics in a signal amplification cascade
We used various analytical and numerical techniques to elucidate signal
propagation in a small enzymatic cascade which is subjected to external and
internal noise. The nonlinear character of catalytic reactions, which underlie
protein signal transduction cascades, renders stochastic signaling dynamics in
cytosol biochemical networks distinct from the usual description of stochastic
dynamics in gene regulatory networks. For a simple 2-step enzymatic cascade
which underlies many important protein signaling pathways, we demonstrated that
the commonly used techniques such as the linear noise approximation and the
Langevin equation become inadequate when the number of proteins becomes too
low. Consequently, we developed a new analytical approximation, based on mixing
the generating function and distribution function approaches, to the solution
of the master equation that describes nonlinear chemical signaling kinetics for
this important class of biochemical reactions. Our techniques work in a much
wider range of protein number fluctuations than the methods used previously. We
found that under certain conditions the burst-phase noise may be injected into
the downstream signaling network dynamics, resulting possibly in unusually
large macroscopic fluctuations. In addition to computing first and second
moments, which is the goal of commonly used analytical techniques, our new
approach provides the full time-dependent probability distributions of the
colored non-Gaussian processes in a nonlinear signal transduction cascade.Comment: 16 pages, 9 figure
The stochastic quasi-steady-state assumption: Reducing the model but not the noise
Highly reactive species at small copy numbers play an important role in many biological reaction networks. We have described previously how these species can be removed from reaction networks using stochastic quasi-steady-state singular perturbation analysis (sQSPA). In this paper we apply sQSPA to three published biological models: the pap operon regulation, a biochemical oscillator, and an intracellular viral infection. These examples demonstrate three different potential benefits of sQSPA. First, rare state probabilities can be accurately estimated from simulation. Second, the method typically results in fewer and better scaled parameters that can be more readily estimated from experiments. Finally, the simulation time can be significantly reduced without sacrificing the accuracy of the solution
An Unstructured Mesh Convergent Reaction-Diffusion Master Equation for Reversible Reactions
The convergent reaction-diffusion master equation (CRDME) was recently
developed to provide a lattice particle-based stochastic reaction-diffusion
model that is a convergent approximation in the lattice spacing to an
underlying spatially-continuous particle dynamics model. The CRDME was designed
to be identical to the popular lattice reaction-diffusion master equation
(RDME) model for systems with only linear reactions, while overcoming the
RDME's loss of bimolecular reaction effects as the lattice spacing is taken to
zero. In our original work we developed the CRDME to handle bimolecular
association reactions on Cartesian grids. In this work we develop several
extensions to the CRDME to facilitate the modeling of cellular processes within
realistic biological domains. Foremost, we extend the CRDME to handle
reversible bimolecular reactions on unstructured grids. Here we develop a
generalized CRDME through discretization of the spatially continuous volume
reactivity model, extending the CRDME to encompass a larger variety of
particle-particle interactions. Finally, we conclude by examining several
numerical examples to demonstrate the convergence and accuracy of the CRDME in
approximating the volume reactivity model.Comment: 35 pages, 9 figures. Accepted, J. Comp. Phys. (2018
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
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
The pseudo-compartment method for coupling PDE and compartment-based models of diffusion
Spatial reaction-diffusion models have been employed to describe many
emergent phenomena in biological systems. The modelling technique most commonly
adopted in the literature implements systems of partial differential equations
(PDEs), which assumes there are sufficient densities of particles that a
continuum approximation is valid. However, due to recent advances in
computational power, the simulation, and therefore postulation, of
computationally intensive individual-based models has become a popular way to
investigate the effects of noise in reaction-diffusion systems in which regions
of low copy numbers exist.
The stochastic models with which we shall be concerned in this manuscript are
referred to as `compartment-based'. These models are characterised by a
discretisation of the computational domain into a grid/lattice of
`compartments'. Within each compartment particles are assumed to be well-mixed
and are permitted to react with other particles within their compartment or to
transfer between neighbouring compartments.
We develop two hybrid algorithms in which a PDE is coupled to a
compartment-based model. Rather than attempting to balance average fluxes, our
algorithms answer a more fundamental question: `how are individual particles
transported between the vastly different model descriptions?' First, we present
an algorithm derived by carefully re-defining the continuous PDE concentration
as a probability distribution. Whilst this first algorithm shows strong
convergence to analytic solutions of test problems, it can be cumbersome to
simulate. Our second algorithm is a simplified and more efficient
implementation of the first, it is derived in the continuum limit over the PDE
region alone. We test our hybrid methods for functionality and accuracy in a
variety of different scenarios by comparing the averaged simulations to
analytic solutions of PDEs for mean concentrations.Comment: MAIN - 24 pages, 10 figures, 1 supplementary file - 3 pages, 2
figure
Hybrid modelling of individual movement and collective behaviour
Mathematical models of dispersal in biological systems are often written in terms of partial differential equations (PDEs) which describe the time evolution of population-level variables (concentrations, densities). A more detailed modelling approach is given by individual-based (agent-based) models which describe the behaviour of each organism. In recent years, an intermediate modelling methodology – hybrid modelling – has been applied to a number of biological systems. These hybrid models couple an individual-based description of cells/animals with a PDEmodel of their environment. In this chapter, we overview hybrid models in the literature with the focus on the mathematical challenges of this modelling approach. The detailed analysis is presented using the example of chemotaxis, where cells move according to extracellular chemicals that can be altered by the cells themselves. In this case, individual-based models of cells are coupled with PDEs for extracellular chemical signals. Travelling waves in these hybrid models are investigated. In particular, we show that in contrary to the PDEs, hybrid chemotaxis models only develop a transient travelling wave
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