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Warne, D. J.

Publications and source records attributed to Warne, D. J..

3 recordsLinked to original sources

Computationally efficient framework for diagnosing, understanding, and predicting biphasic population growth

Throughout the life sciences, biological populations undergo multiple phases of growth, often referred to as biphasic growth for the commonly-encountered situation involving two phases. Biphasic population growth occurs over a massive range of spatial and temporal scales, ranging from microscopic growth of tumours over several days, to decades-long re-growth of corals in coral reefs that can extend for hundreds of kilometres. Different mathematical models and statistical methods are used to diagnose, understand, and predict biphasic growth. Common approaches can lead to inaccurate predictions of future growth that may result in inappropriate management and intervention strategies being implemented. Here we develop a very general computationally efficient framework, based on profile likelihood analysis, for diagnosing, understanding, and predicting biphasic population growth. The two key components of the framework are: (i) an efficient method to form approximate confidence intervals for the change point of the growth dynamics and model parameters; and, (ii) parameter-wise profile predictions that systematically reveal the influence of individual model parameters on predictions. To illustrate our framework we explore real-world case studies across the life sciences.

systems biology↗

Parameter identifiability and model selection for sigmoid population growth models

Sigmoid growth models, such as the logistic, Gompertz and Richards models, are widely used to study population dynamics ranging from microscopic populations of cancer cells, to continental-scale human populations. Fundamental questions about model selection and parameter estimation are critical if these models are to be used to make practical inferences. However, the question of parameter identifiability - whether a data set contains sufficient information to give unique or sufficiently precise parameter estimates - is often overlooked. We use a profile-likelihood approach to explore practical parameter identifiability using data describing the re-growth of hard coral. With this approach, we explore the relationship between parameter identifiability and model misspecification, finding that the logistic growth model does not suffer identifiability issues for the type of data we consider whereas the Gompertz and Richards models encounter practical non-identifiability issues. This analysis of parameter identifiability and model selection is important because different growth models are used within areas of the biological modelling literature without necessarily considering whether parameters are identifiable, or checking statistical assumptions underlying model adequacy. Standard practices that do not consider parameter identifiability can lead to unreliable or imprecise parameter estimates and potentially misleading mechanistic interpretations. While tools developed here focus on three standard sigmoid growth models only, our theoretical developments are applicable to any sigmoid growth model and any relevant data set. MATLAB implementations of all software are available on GitHub.

ecology↗

Listen to the noise: identifiability analysis for stochastic differential equation models in systems biology

Mathematical models are routinely calibrated to experimental data, with goals ranging from building predictive models to quantifying parameters that cannot be measured. Whether or not reliable parameter estimates are obtainable from the available data can easily be overlooked. Such issues of parameter identifiability have important ramifications for both the predictive power of a model, and the mechanistic insight that can be obtained. Identifiability analysis is well-established for deterministic, ordinary differential equation (ODE) models, but there are no commonly-adopted methods for analysing identifiability in stochastic models. We provide an accessible introduction to identifiability analysis and demonstrate how existing ideas for analysis of ODE models can be applied to stochastic differential equation (SDE) models through four practical case studies. To assess structural identifiability, we study ODEs that describe the statistical moments of the stochastic process using open-source software tools. Using practically-motivated synthetic data and Markov-chain Monte Carlo (MCMC) methods, we assess parameter identifiability in the context of available data. Our analysis shows that SDE models can often extract more information about parameters than deterministic descriptions. All code used to perform the analysis is available on Github.

systems biology↗