21,563 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
Parameter estimation and inference for stochastic reaction-diffusion systems: application to morphogenesis in D. melanogaster
Background: Reaction-diffusion systems are frequently used in systems biology to model developmental and signalling processes. In many applications, count numbers of the diffusing molecular species are very low, leading to the need to explicitly model the inherent variability using stochastic methods. Despite their importance and frequent use, parameter estimation for both deterministic and stochastic reaction-diffusion systems is still a challenging problem.
Results: We present a Bayesian inference approach to solve both the parameter and state estimation problem for stochastic reaction-diffusion systems. This allows a determination of the full posterior distribution of the parameters (expected values and uncertainty). We benchmark the method by illustrating it on a simple synthetic experiment. We then test the method on real data about the diffusion of the morphogen Bicoid in Drosophila melanogaster. The results show how the precision with which parameters can be inferred varies dramatically, indicating that the ability to infer full posterior distributions on the parameters can have important experimental design consequences.
Conclusions: The results obtained demonstrate the feasibility and potential advantages of applying a Bayesian approach to parameter estimation in stochastic reaction-diffusion systems. In particular, the ability to estimate credibility intervals associated with parameter estimates can be precious for experimental design. Further work, however, will be needed to ensure the method can scale up to larger problems
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
MCMC inference for Markov Jump Processes via the Linear Noise Approximation
Bayesian analysis for Markov jump processes is a non-trivial and challenging
problem. Although exact inference is theoretically possible, it is
computationally demanding thus its applicability is limited to a small class of
problems. In this paper we describe the application of Riemann manifold MCMC
methods using an approximation to the likelihood of the Markov jump process
which is valid when the system modelled is near its thermodynamic limit. The
proposed approach is both statistically and computationally efficient while the
convergence rate and mixing of the chains allows for fast MCMC inference. The
methodology is evaluated using numerical simulations on two problems from
chemical kinetics and one from systems biology
Efficient statistical inference for stochastic reaction processes
We address the problem of estimating unknown model parameters and state
variables in stochastic reaction processes when only sparse and noisy
measurements are available. Using an asymptotic system size expansion for the
backward equation we derive an efficient approximation for this problem. We
demonstrate the validity of our approach on model systems and generalize our
method to the case when some state variables are not observed.Comment: 4 pages, 2 figures, 2 tables; typos corrected, remark about Kalman
smoother adde
Birth/birth-death processes and their computable transition probabilities with biological applications
Birth-death processes track the size of a univariate population, but many
biological systems involve interaction between populations, necessitating
models for two or more populations simultaneously. A lack of efficient methods
for evaluating finite-time transition probabilities of bivariate processes,
however, has restricted statistical inference in these models. Researchers rely
on computationally expensive methods such as matrix exponentiation or Monte
Carlo approximation, restricting likelihood-based inference to small systems,
or indirect methods such as approximate Bayesian computation. In this paper, we
introduce the birth(death)/birth-death process, a tractable bivariate extension
of the birth-death process. We develop an efficient and robust algorithm to
calculate the transition probabilities of birth(death)/birth-death processes
using a continued fraction representation of their Laplace transforms. Next, we
identify several exemplary models arising in molecular epidemiology,
macro-parasite evolution, and infectious disease modeling that fall within this
class, and demonstrate advantages of our proposed method over existing
approaches to inference in these models. Notably, the ubiquitous stochastic
susceptible-infectious-removed (SIR) model falls within this class, and we
emphasize that computable transition probabilities newly enable direct
inference of parameters in the SIR model. We also propose a very fast method
for approximating the transition probabilities under the SIR model via a novel
branching process simplification, and compare it to the continued fraction
representation method with application to the 17th century plague in Eyam.
Although the two methods produce similar maximum a posteriori estimates, the
branching process approximation fails to capture the correlation structure in
the joint posterior distribution
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