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

Training Echo State Networks with Regularization through Dimensionality Reduction

In this paper we introduce a new framework to train an Echo State Network to predict real valued time-series. The method consists in projecting the output of the internal layer of the network on a space with lower dimensionality, before training the output layer to learn the target task. Notably, we enforce a regularization constraint that leads to better generalization capabilities. We evaluate the performances of our approach on several benchmark tests, using different techniques to train the readout of the network, achieving superior predictive performance when using the proposed framework. Finally, we provide an insight on the effectiveness of the implemented mechanics through a visualization of the trajectory in the phase space and relying on the methodologies of nonlinear time-series analysis. By applying our method on well known chaotic systems, we provide evidence that the lower dimensional embedding retains the dynamical properties of the underlying system better than the full-dimensional internal states of the network

Determining Structurally Identifiable Parameter Combinations Using Subset Profiling

Identifiability is a necessary condition for successful parameter estimation of dynamic system models. A major component of identifiability analysis is determining the identifiable parameter combinations, the functional forms for the dependencies between unidentifiable parameters. Identifiable combinations can help in model reparameterization and also in determining which parameters may be experimentally measured to recover model identifiability. Several numerical approaches to determining identifiability of differential equation models have been developed, however the question of determining identifiable combinations remains incompletely addressed. In this paper, we present a new approach which uses parameter subset selection methods based on the Fisher Information Matrix, together with the profile likelihood, to effectively estimate identifiable combinations. We demonstrate this approach on several example models in pharmacokinetics, cellular biology, and physiology

Stochastic ordinary differential equations in applied and computational mathematics

Using concrete examples, we discuss the current and potential use of stochastic ordinary differential equations (SDEs) from the perspective of applied and computational mathematics. Assuming only a minimal background knowledge in probability and stochastic processes, we focus on aspects that distinguish SDEs from their deterministic counterparts. To illustrate a multiscale modelling framework, we explain how SDEs arise naturally as diffusion limits in the type of discrete-valued stochastic models used in chemical kinetics, population dynamics, and, most topically, systems biology. We outline some key issues in existence, uniqueness and stability that arise when SDEs are used as physical models, and point out possible pitfalls. We also discuss the use of numerical methods to simulate trajectories of an SDE and explain how both weak and strong convergence properties are relevant for highly-efficient multilevel Monte Carlo simulations. We flag up what we believe to be key topics for future research, focussing especially on nonlinear models, parameter estimation, model comparison and multiscale simulation

Estimating Threshold Effects of Generic Fluid Milk and Cheese Advertising

Replaced with revised version of paper 08/01/06.Livestock Production/Industries, Marketing,

Survey of decentralized control methods

An overview is presented of the types of problems that are being considered by control theorists in the area of dynamic large scale systems with emphasis on decentralized control strategies. Approaches that deal directly with decentralized decision making for large scale systems are discussed. It is shown that future advances in decentralized system theory are intimately connected with advances in the stochastic control problem with nonclassical information pattern. The basic assumptions and mathematical tools associated with the latter are summarized, and recommendations concerning future research are presented

A comparison of methods to determine neuronal phase-response curves

The phase-response curve (PRC) is an important tool to determine the excitability type of single neurons which reveals consequences for their synchronizing properties. We review five methods to compute the PRC from both model data and experimental data and compare the numerically obtained results from each method. The main difference between the methods lies in the reliability which is influenced by the fluctuations in the spiking data and the number of spikes available for analysis. We discuss the significance of our results and provide guidelines to choose the best method based on the available data.Comment: PDFLatex, 16 pages, 7 figures