2,359 research outputs found
Simulation and inference algorithms for stochastic biochemical reaction networks: from basic concepts to state-of-the-art
Stochasticity is a key characteristic of intracellular processes such as gene
regulation and chemical signalling. Therefore, characterising stochastic
effects in biochemical systems is essential to understand the complex dynamics
of living things. Mathematical idealisations of biochemically reacting systems
must be able to capture stochastic phenomena. While robust theory exists to
describe such stochastic models, the computational challenges in exploring
these models can be a significant burden in practice since realistic models are
analytically intractable. Determining the expected behaviour and variability of
a stochastic biochemical reaction network requires many probabilistic
simulations of its evolution. Using a biochemical reaction network model to
assist in the interpretation of time course data from a biological experiment
is an even greater challenge due to the intractability of the likelihood
function for determining observation probabilities. These computational
challenges have been subjects of active research for over four decades. In this
review, we present an accessible discussion of the major historical
developments and state-of-the-art computational techniques relevant to
simulation and inference problems for stochastic biochemical reaction network
models. Detailed algorithms for particularly important methods are described
and complemented with MATLAB implementations. As a result, this review provides
a practical and accessible introduction to computational methods for stochastic
models within the life sciences community
Scalable Inference for Markov Processes with Intractable Likelihoods
Bayesian inference for Markov processes has become increasingly relevant in
recent years. Problems of this type often have intractable likelihoods and
prior knowledge about model rate parameters is often poor. Markov Chain Monte
Carlo (MCMC) techniques can lead to exact inference in such models but in
practice can suffer performance issues including long burn-in periods and poor
mixing. On the other hand approximate Bayesian computation techniques can allow
rapid exploration of a large parameter space but yield only approximate
posterior distributions. Here we consider the combined use of approximate
Bayesian computation (ABC) and MCMC techniques for improved computational
efficiency while retaining exact inference on parallel hardware
Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems
Approximate Bayesian computation methods can be used to evaluate posterior
distributions without having to calculate likelihoods. In this paper we discuss
and apply an approximate Bayesian computation (ABC) method based on sequential
Monte Carlo (SMC) to estimate parameters of dynamical models. We show that ABC
SMC gives information about the inferability of parameters and model
sensitivity to changes in parameters, and tends to perform better than other
ABC approaches. The algorithm is applied to several well known biological
systems, for which parameters and their credible intervals are inferred.
Moreover, we develop ABC SMC as a tool for model selection; given a range of
different mathematical descriptions, ABC SMC is able to choose the best model
using the standard Bayesian model selection apparatus.Comment: 26 pages, 9 figure
Global parameter identification of stochastic reaction networks from single trajectories
We consider the problem of inferring the unknown parameters of a stochastic
biochemical network model from a single measured time-course of the
concentration of some of the involved species. Such measurements are available,
e.g., from live-cell fluorescence microscopy in image-based systems biology. In
addition, fluctuation time-courses from, e.g., fluorescence correlation
spectroscopy provide additional information about the system dynamics that can
be used to more robustly infer parameters than when considering only mean
concentrations. Estimating model parameters from a single experimental
trajectory enables single-cell measurements and quantification of cell--cell
variability. We propose a novel combination of an adaptive Monte Carlo sampler,
called Gaussian Adaptation, and efficient exact stochastic simulation
algorithms that allows parameter identification from single stochastic
trajectories. We benchmark the proposed method on a linear and a non-linear
reaction network at steady state and during transient phases. In addition, we
demonstrate that the present method also provides an ellipsoidal volume
estimate of the viable part of parameter space and is able to estimate the
physical volume of the compartment in which the observed reactions take place.Comment: Article in print as a book chapter in Springer's "Advances in Systems
Biology
Simulation-based model selection for dynamical systems in systems and population biology
Computer simulations have become an important tool across the biomedical
sciences and beyond. For many important problems several different models or
hypotheses exist and choosing which one best describes reality or observed data
is not straightforward. We therefore require suitable statistical tools that
allow us to choose rationally between different mechanistic models of e.g.
signal transduction or gene regulation networks. This is particularly
challenging in systems biology where only a small number of molecular species
can be assayed at any given time and all measurements are subject to
measurement uncertainty. Here we develop such a model selection framework based
on approximate Bayesian computation and employing sequential Monte Carlo
sampling. We show that our approach can be applied across a wide range of
biological scenarios, and we illustrate its use on real data describing
influenza dynamics and the JAK-STAT signalling pathway. Bayesian model
selection strikes a balance between the complexity of the simulation models and
their ability to describe observed data. The present approach enables us to
employ the whole formal apparatus to any system that can be (efficiently)
simulated, even when exact likelihoods are computationally intractable.Comment: This article is in press in Bioinformatics, 2009. Advance Access is
available on Bioinformatics webpag
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