3,851 research outputs found
Marginal process framework: A model reduction tool for Markov jump processes
Markov jump process models have many applications across science. Often,
these models are defined on a state-space of product form and only one of the
components of the process is of direct interest. In this paper, we extend the
marginal process framework, which provides a marginal description of the
component of interest, to the case of fully coupled processes. We use entropic
matching to obtain a finite-dimensional approximation of the filtering
equation, which governs the transition rates of the marginal process. The
resulting equations can be seen as a combination of two projection operations
applied to the full master equation, so that we obtain a principled model
reduction framework. We demonstrate the resulting reduced description on the
totally asymmetric exclusion process. An important class of Markov jump
processes are stochastic reaction networks, which have applications in chemical
and biomolecular kinetics, ecological models and models of social networks. We
obtain a particularly simple instantiation of the marginal process framework
for mass-action systems by using product-Poisson distributions for the
approximate solution of the filtering equation. We investigate the resulting
approximate marginal process analytically and numerically.Comment: 16 pages, 5 figures; accepted for publication in Physical Review
Uncoupled Analysis of Stochastic Reaction Networks in Fluctuating Environments
The dynamics of stochastic reaction networks within cells are inevitably
modulated by factors considered extrinsic to the network such as for instance
the fluctuations in ribsome copy numbers for a gene regulatory network. While
several recent studies demonstrate the importance of accounting for such
extrinsic components, the resulting models are typically hard to analyze. In
this work we develop a general mathematical framework that allows to uncouple
the network from its dynamic environment by incorporating only the
environment's effect onto the network into a new model. More technically, we
show how such fluctuating extrinsic components (e.g., chemical species) can be
marginalized in order to obtain this decoupled model. We derive its
corresponding process- and master equations and show how stochastic simulations
can be performed. Using several case studies, we demonstrate the significance
of the approach. For instance, we exemplarily formulate and solve a marginal
master equation describing the protein translation and degradation in a
fluctuating environment.Comment: 7 pages, 4 figures, Appendix attached as SI.pdf, under submissio
Approximation and inference methods for stochastic biochemical kinetics-a tutorial review
Stochastic fluctuations of molecule numbers are ubiquitous in biological systems. Important examples include gene expression and enzymatic processes in living cells. Such systems are typically modelled as chemical reaction networks whose dynamics are governed by the chemical master equation. Despite its simple structure, no analytic solutions to the chemical master equation are known for most systems. Moreover, stochastic simulations are computationally expensive, making systematic analysis and statistical inference a challenging task. Consequently, significant effort has been spent in recent decades on the development of efficient approximation and inference methods. This article gives an introduction to basic modelling concepts as well as an overview of state of the art methods. First, we motivate and introduce deterministic and stochastic methods for modelling chemical networks, and give an overview of simulation and exact solution methods. Next, we discuss several approximation methods, including the chemical Langevin equation, the system size expansion, moment closure approximations, time-scale separation approximations and hybrid methods. We discuss their various properties and review recent advances and remaining challenges for these methods. We present a comparison of several of these methods by means of a numerical case study and highlight some of their respective advantages and disadvantages. Finally, we discuss the problem of inference from experimental data in the Bayesian framework and review recent methods developed the literature. In summary, this review gives a self-contained introduction to modelling, approximations and inference methods for stochastic chemical kinetics
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
Mean-Field approximation and Quasi-Equilibrium reduction of Markov Population Models
Markov Population Model is a commonly used framework to describe stochastic
systems. Their exact analysis is unfeasible in most cases because of the state
space explosion. Approximations are usually sought, often with the goal of
reducing the number of variables. Among them, the mean field limit and the
quasi-equilibrium approximations stand out. We view them as techniques that are
rooted in independent basic principles. At the basis of the mean field limit is
the law of large numbers. The principle of the quasi-equilibrium reduction is
the separation of temporal scales. It is common practice to apply both limits
to an MPM yielding a fully reduced model. Although the two limits should be
viewed as completely independent options, they are applied almost invariably in
a fixed sequence: MF limit first, QE-reduction second. We present a framework
that makes explicit the distinction of the two reductions, and allows an
arbitrary order of their application. By inverting the sequence, we show that
the double limit does not commute in general: the mean field limit of a
time-scale reduced model is not the same as the time-scale reduced limit of a
mean field model. An example is provided to demonstrate this phenomenon.
Sufficient conditions for the two operations to be freely exchangeable are also
provided
Entropy: The Markov Ordering Approach
The focus of this article is on entropy and Markov processes. We study the
properties of functionals which are invariant with respect to monotonic
transformations and analyze two invariant "additivity" properties: (i)
existence of a monotonic transformation which makes the functional additive
with respect to the joining of independent systems and (ii) existence of a
monotonic transformation which makes the functional additive with respect to
the partitioning of the space of states. All Lyapunov functionals for Markov
chains which have properties (i) and (ii) are derived. We describe the most
general ordering of the distribution space, with respect to which all
continuous-time Markov processes are monotonic (the {\em Markov order}). The
solution differs significantly from the ordering given by the inequality of
entropy growth. For inference, this approach results in a convex compact set of
conditionally "most random" distributions.Comment: 50 pages, 4 figures, Postprint version. More detailed discussion of
the various entropy additivity properties and separation of variables for
independent subsystems in MaxEnt problem is added in Section 4.2.
Bibliography is extende
Markovian Dynamics on Complex Reaction Networks
Complex networks, comprised of individual elements that interact with each
other through reaction channels, are ubiquitous across many scientific and
engineering disciplines. Examples include biochemical, pharmacokinetic,
epidemiological, ecological, social, neural, and multi-agent networks. A common
approach to modeling such networks is by a master equation that governs the
dynamic evolution of the joint probability mass function of the underling
population process and naturally leads to Markovian dynamics for such process.
Due however to the nonlinear nature of most reactions, the computation and
analysis of the resulting stochastic population dynamics is a difficult task.
This review article provides a coherent and comprehensive coverage of recently
developed approaches and methods to tackle this problem. After reviewing a
general framework for modeling Markovian reaction networks and giving specific
examples, the authors present numerical and computational techniques capable of
evaluating or approximating the solution of the master equation, discuss a
recently developed approach for studying the stationary behavior of Markovian
reaction networks using a potential energy landscape perspective, and provide
an introduction to the emerging theory of thermodynamic analysis of such
networks. Three representative problems of opinion formation, transcription
regulation, and neural network dynamics are used as illustrative examples.Comment: 52 pages, 11 figures, for freely available MATLAB software, see
http://www.cis.jhu.edu/~goutsias/CSS%20lab/software.htm
Linear mapping approximation of gene regulatory networks with stochastic dynamics
The intractability of most stochastic models of gene regulatory networks (GRNs) limits their utility. Here, the authors present a linear-mapping approximation mapping models onto simpler ones, giving approximate but accurate analytic or semi- analytic solutions for a wide range of model GRNs
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