Abstract

BackgroundReaction-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.ResultsWe 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.ConclusionsThe 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.

Highlights

  • Reaction-diffusion systems are frequently used in systems biology to model developmental and signalling processes

  • Parameter estimation problems are becoming increasingly important in systems biology

  • We present an approach to state inference and parameter estimation for stochastic reactiondiffusion systems

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Summary

Introduction

Reaction-diffusion systems are frequently used in systems biology to model developmental and signalling processes. 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. If we assume that production of c can happen only in a specific region of the embryo, after a transient period, the steady state solution will exhibit a gradient in the concentration of c While this is a very simple example, it is already non-trivial due to the interplay of spatial and temporal dynamics. This example highlights another important feature of the reaction-diffusion systems encountered in systems biology, i.e. the fact that they necessarily will involve low counts of molecules

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