arXiv subjects

Matthew J. Simpson

Publications and source records attributed to Matthew J. Simpson.

At least 19 recordsLinked to original sources

arXiv2025

Continuum models describing probabilistic motion of tagged agents in exclusion processes

Lattice-based random walk models are widely used to study populations of migrating cells with motility bias and proliferation. Crowding is typically represented by volume exclusion, where each lattice site can be occupied by at most one agent and conflicting moves are aborted. This framework enables simulations that yield both population-level spatiotemporal agent density profiles and individual agent trajectories, comparable to experimental cell-tracking data. Previous continuum models for tagged-agent trajectories captured trajectory information only, and overlooked any measure of variability. This is an important limitation since trajectory data is inherently variable. To address this limitation, here we derive partial differential equations for the probability density function of tagged-agent trajectories. This continuum description has a clear physical interpretation, agrees well with distributional data from stochastic simulations, reveals the role of stochasticity in different contexts, and generalises to multiple subpopulations of distinct agents.

q-bio.PE↗

arXiv2024

Random walk models in the life sciences: including births, deaths and local interactions

Random walks and related spatial stochastic models have been used in a range of application areas including animal and plant ecology, infectious disease epidemiology, developmental biology, wound healing, and oncology. Classical random walk models assume that all individuals in a population behave independently, ignoring local physical and biological interactions. This assumption simplifies the mathematical description of the population considerably, enabling continuum-limit descriptions to be derived and used in model analysis and fitting. However, interactions between individuals can have a crucial impact on population-level behaviour. In recent decades, research has increasingly been directed towards models that include interactions, including physical crowding effects and local biological processes such as adhesion, competition, dispersal, predation and adaptive directional bias. In this article, we review the progress that has been made with models of interacting individuals. We aim to provide an overview that is accessible to researchers in application areas, as well as to specialist modellers. We focus particularly on derivation of asymptotically exact or approximate continuum-limit descriptions and simplified deterministic models of mean-field behaviour and resulting spatial patterns. We provide worked examples and illustrative results of selected models. We conclude with a discussion of current areas of focus and future challenges.

q-bio.PE↗

arXiv2024

Efficient inference for differential equation models without numerical solvers

Parameter inference is essential when interpreting observational data using mathematical models. Standard inference methods for differential equation models typically rely on obtaining repeated numerical solutions of the differential equation(s). Recent results have explored how numerical truncation error can have major, detrimental, and sometimes hidden impacts on likelihood-based inference by introducing false local maxima into the log-likelihood function. We present a straightforward approach for inference that eliminates the need for solving the underlying differential equations, thereby completely avoiding the impact of truncation error. Open-access Jupyter notebooks, available on GitHub, allow others to implement this method for a broad class of widely-used models to interpret biological data.

stat.ME↗

arXiv2024

Mathematical modelling and uncertainty quantification for analysis of biphasic coral reef recovery patterns

Coral reefs are increasingly subjected to major disturbances threatening the health of marine ecosystems. Substantial research underway to develop intervention strategies that assist reefs in recovery from, and resistance to, inevitable future climate and weather extremes. To assess potential benefits of interventions, mechanistic understanding of coral reef recovery and resistance patterns is essential. Recent evidence suggests that more than half of the reefs surveyed across the Great Barrier Reef (GBR) exhibit deviations from standard recovery modelling assumptions when the initial coral cover is low ($\leq 10$\%). New modelling is necessary to account for these observed patterns to better inform management strategies. We consider a new model for reef recovery at the coral cover scale that accounts for biphasic recovery patterns. The model is based on a multispecies Richards' growth model that includes a change point in the recovery patterns. Bayesian inference is applied for uncertainty quantification of key parameters for assessing reef health and recovery patterns. This analysis is applied to benthic survey data from the Australian Institute of Marine Sciences (AIMS). We demonstrate agreement between model predictions and data across every recorded recovery trajectory with at least two years of observations following disturbance events occurring between 1992--2020. This new approach will enable new insights into the biological, ecological and environmental factors that contribute to the duration and severity of biphasic coral recovery patterns across the GBR. These new insights will help to inform managements and monitoring practice to mitigate the impacts of climate change on coral reefs.

stat.AP↗

arXiv2024

Mechanical cell interactions on curved interfaces

We propose a simple mathematical model to describe the mechanical relaxation of cells within a curved epithelial tissue layer represented by an arbitrary curve in two-dimensional space. This model generalises previous one-dimensional models of flat epithelia to investigate the influence of curvature for mechanical relaxation. We represent the mechanics of a cell body either by straight springs, or by curved springs that follow the curve's shape. To understand the collective dynamics of the cells, we devise an appropriate continuum limit in which the number of cells and the length of the substrate are constant but the number of springs tends to infinity. In this limit, cell density is governed by a diffusion equation in arc length coordinates, where diffusion may be linear or nonlinear depending on the choice of the spring restoring force law. Our results have important implications about modelling cells on curved geometries: (i) curved and straight springs can lead to different dynamics when there is a finite number of springs, but they both converge quadratically to the dynamics governed by the diffusion equation; (ii) in the continuum limit, the curvature of the tissue does not affect the mechanical relaxation of cells within the layer nor their tangential stress; (iii) a cell's normal stress depends on curvature due to surface tension induced by the tangential forces. Normal stress enables cells to sense substrate curvature at length scales much larger than their cell body, and could induce curvature dependences in experiments.

nlin.CG↗

arXiv2024

A generalised sigmoid population growth model with energy dependence: application to quantify the tipping point for Antarctic shallow seabed algae

Sigmoid growth models are often used to study population dynamics. The size of a population at equilibrium commonly depends explicitly on the availability of resources, such as an energy or nutrient source, which is not explicit in standard sigmoid growth models. A simple generalised extension of sigmoid growth models is introduced that can explicitly account for this resource-dependence, demonstrated by three examples of this family of models of increasing mathematical complexity. Each model is calibrated and compared to observed data for algae under sea-ice in Antarctic coastal waters. It was found that through careful construction, models satisfying the proposed framework can estimate key properties of a sea-ice break-out controlled tipping point for the algae, which cannot be estimated using standard sigmoid growth models. The proposed broader family of energy-dependent sigmoid growth models likely has usage in many population growth contexts where resources limit population size.

q-bio.PE↗

arXiv2024

Structured methods for parameter inference and uncertainty quantification for mechanistic models in the life sciences

Parameter inference and uncertainty quantification are important steps when relating mathematical models to real-world observations, and when estimating uncertainty in model predictions. However, methods for doing this can be computationally expensive, particularly when the number of unknown model parameters is large. The aim of this study is to develop and test an efficient profile likelihood-based method, which takes advantage of the structure of the mathematical model being used. We do this by identifying specific parameters that affect model output in a known way, such as a linear scaling. We illustrate the method by applying it to three caricature models from different areas of the life sciences: (i) a predator-prey model from ecology; (ii) a compartment-based epidemic model from health sciences; and, (iii) an advection-diffusion-reaction model describing transport of dissolved solutes from environmental science. We show that the new method produces results of comparable accuracy to existing profile likelihood methods, but with substantially fewer evaluations of the forward model. We conclude that our method could provide a much more efficient approach to parameter inference for models where a structured approach is feasible. Code to apply the new method to user-supplied models and data is provided via a publicly accessible repository.

q-bio.QM↗

arXiv2023

Pushing coarse-grained models beyond the continuum limit using equation learning

Mathematical modelling of biological population dynamics often involves proposing high fidelity discrete agent-based models that capture stochasticity and individual-level processes. These models are often considered in conjunction with an approximate coarse-grained differential equation that captures population-level features only. These coarse-grained models are only accurate in certain asymptotic parameter regimes, such as enforcing that the time scale of individual motility far exceeds the time scale of birth/death processes. When these coarse-grained models are accurate, the discrete model still abides by conservation laws at the microscopic level, which implies that there is some macroscopic conservation law that can describe the macroscopic dynamics. In this work, we introduce an equation learning framework to find accurate coarse-grained models when standard continuum limit approaches are inaccurate. We demonstrate our approach using a discrete mechanical model of epithelial tissues, considering a series of four case studies that consider problems with and without free boundaries, and with and without proliferation, illustrating how we can learn macroscopic equations describing mechanical relaxation, cell proliferation, and the equation governing the dynamics of the free boundary of the tissue. While our presentation focuses on this biological application, our approach is more broadly applicable across a range of scenarios where discrete models are approximated by approximate continuum-limit descriptions. All code and data to reproduce this work are available at https://github.com/DanielVandH/StepwiseEQL.jl.

math.DS↗

arXiv2023

Implementing measurement error models with mechanistic mathematical models in a likelihood-based framework for estimation, identifiability analysis, and prediction in the life sciences

Throughout the life sciences we routinely seek to interpret measurements and observations using parameterised mechanistic mathematical models. A fundamental and often overlooked choice in this approach involves relating the solution of a mathematical model with noisy and incomplete measurement data. This is often achieved by assuming that the data are noisy measurements of the solution of a deterministic mathematical model, and that measurement errors are additive and normally distributed. While this assumption of additive Gaussian noise is extremely common and simple to implement and interpret, it is often unjustified and can lead to poor parameter estimates and non-physical predictions. One way to overcome this challenge is to implement a different measurement error model. In this review, we demonstrate how to implement a range of measurement error models in a likelihood-based framework for estimation, identifiability analysis, and prediction, called Profile-Wise Analysis. This frequentist approach to uncertainty quantification for mechanistic models leverages the profile likelihood for targeting parameters and understanding their influence on predictions. Case studies, motivated by simple caricature models routinely used in systems biology and mathematical biology literature, illustrate how the same ideas apply to different types of mathematical models. Open-source Julia code to reproduce results is available on GitHub.

q-bio.QM↗

arXiv2023

Exact sharp-fronted solutions for nonlinear diffusion on evolving domains

Models of diffusive processes that occur on evolving domains are frequently employed to describe biological and physical phenomena, such as diffusion within expanding tissues or substrates. Previous investigations into these models either report numerical solutions or require an assumption of linear diffusion to determine exact solutions. Unfortunately, numerical solutions do not reveal the relationship between the model parameters and the solution features. Additionally, experimental observations typically report the presence of sharp fronts, which are not captured by linear diffusion. Here we address both limitations by presenting exact sharp-fronted solutions to a model of degenerate nonlinear diffusion on a growing domain. We obtain the solution by identifying a series of transformations that converts the model of a nonlinear diffusive process on an evolving domain to a nonlinear diffusion equation on a fixed domain, which admits known exact solutions for certain choices of diffusivity functions. We determine expressions for critical time scales and domain growth rates such that the diffusive population never reaches the domain boundaries and hence the solution remains valid.

q-bio.PE↗

arXiv2023

Generalised likelihood profiles for models with intractable likelihoods

Likelihood profiling is an efficient and powerful frequentist approach for parameter estimation, uncertainty quantification and practical identifiablity analysis. Unfortunately, these methods cannot be easily applied for stochastic models without a tractable likelihood function. Such models are typical in many fields of science, rendering these classical approaches impractical in these settings. To address this limitation, we develop a new approach to generalising the methods of likelihood profiling for situations when the likelihood cannot be evaluated but stochastic simulations of the assumed data generating process are possible. Our approach is based upon recasting developments from generalised Bayesian inference into a frequentist setting. We derive a method for constructing generalised likelihood profiles and calibrating these profiles to achieve desired frequentist coverage for a given coverage level. We demonstrate the performance of our method on realistic examples from the literature and highlight the capability of our approach for the purpose of practical identifability analysis for models with intractable likelihoods.

stat.ME↗

arXiv2023

Simplified models of diffusion in radially-symmetric geometries

We consider diffusion-controlled release of particles from $d$-dimensional radially-symmetric geometries. A quantity commonly used to characterise such diffusive processes is the proportion of particles remaining within the geometry over time, denoted as $P(t)$. The stochastic approach for computing $P(t)$ is time-consuming and lacks analytical insight into key parameters while the continuum approach yields complicated expressions for $P(t)$ that obscure the influence of key parameters and complicate the process of fitting experimental release data. In this work, to address these issues, we develop several simple surrogate models to approximate $P(t)$ by matching moments with the continuum analogue of the stochastic diffusion model. Surrogate models are developed for homogeneous slab, circular, annular, spherical and spherical shell geometries with a constant particle movement probability and heterogeneous slab, circular, annular and spherical geometries, comprised of two concentric layers with different particle movement probabilities. Each model is easy to evaluate, agrees well with both stochastic and continuum calculations of $P(t)$ and provides analytical insight into the key parameters of the diffusive transport system: dimension, diffusivity, geometry and boundary conditions.

physics.bio-ph↗

arXiv2023

Exact solutions for diffusive transport on heterogeneous growing domains

From the smallest biological systems to the largest cosmological structures, spatial domains undergo expansion and contraction. Within these growing domains, diffusive transport is a common phenomenon. Mathematical models have been widely employed to investigate diffusive processes on growing domains. However, a standard assumption is that the domain growth is spatially uniform. There are many relevant examples where this is not the case, such as the colonisation of growing gut tissue by neural crest cells. As such, it is not straightforward to disentangle the individual roles of heterogeneous growth and diffusive transport. Here we present exact solutions to models of diffusive transport on domains undergoing spatially non-uniform growth. The exact solutions are obtained via a combination of transformation, convolution and superposition techniques. We verify the accuracy of these solutions via comparison with simulations of a corresponding lattice-based random walk. We explore various domain growth functions, including linear growth, exponential growth and contraction, and oscillatory growth. Provided the domain size remains positive, we find that the derived solutions are valid. The exact solutions reveal the relationship between model parameters, such as the diffusivity and the type and rate of domain growth, and key statistics, such as the survival and splitting probabilities.

q-bio.PE↗

arXiv2022

Efficient inference and identifiability analysis for differential equation models with random parameters

Heterogeneity is a dominant factor in the behaviour of many biological processes. Despite this, it is common for mathematical and statistical analyses to ignore biological heterogeneity as a source of variability in experimental data. Therefore, methods for exploring the identifiability of models that explicitly incorporate heterogeneity through variability in model parameters are relatively underdeveloped. We develop a new likelihood-based framework, based on moment matching, for inference and identifiability analysis of differential equation models that capture biological heterogeneity through parameters that vary according to probability distributions. As our novel method is based on an approximate likelihood function, it is highly flexible; we demonstrate identifiability analysis using both a frequentist approach based on profile likelihood, and a Bayesian approach based on Markov-chain Monte Carlo. Through three case studies, we demonstrate our method by providing a didactic guide to inference and identifiability analysis of hyperparameters that relate to the statistical moments of model parameters from independent observed data. Our approach has a computational cost comparable to analysis of models that neglect heterogeneity, a significant improvement over many existing alternatives. We demonstrate how analysis of random parameter models can aid better understanding of the sources of heterogeneity from biological data.

stat.ME↗

arXiv2022

Pattern formation and front stability for a moving-boundary model of biological invasion and recession

We investigate pattern formation in a two-dimensional (2D) Fisher--Stefan model, which involves solving the Fisher--KPP equation on a compactly-supported region with a moving boundary. By combining the Fisher--KPP and classical Stefan theory, the Fisher--Stefan model alleviates two limitations of the Fisher--KPP equation for biological populations. In this work, we investigate whether the 2D Fisher--Stefan model predicts pattern formation, by analysing the linear stability of planar travelling wave solutions to sinusoidal transverse perturbations. Planar fronts of the Fisher--KPP equation are linearly stable. Similarly, we demonstrate that invading planar fronts ($c > 0$) of the Fisher--Stefan model are linearly stable to perturbations of all wave numbers. However, our analysis demonstrates that receding planar fronts ($c < 0$) of the Fisher--Stefan model are linearly unstable for all wave numbers. This is analogous to unstable solutions for planar solidification in the classical Stefan problem. Introducing a surface tension regularisation stabilises receding fronts for short-wavelength perturbations, giving rise to a range of unstable modes and a most unstable wave number. We supplement linear stability analysis with level-set numerical solutions that corroborate theoretical results. Overall, front instability in the Fisher--Stefan model suggests a new mechanism for pattern formation in receding biological populations.

physics.bio-ph↗

arXiv2022

Multifidelity multilevel Monte Carlo to accelerate approximate Bayesian parameter inference for partially observed stochastic processes

Models of stochastic processes are widely used in almost all fields of science. Theory validation, parameter estimation, and prediction all require model calibration and statistical inference using data. However, data are almost always incomplete observations of reality. This leads to a great challenge for statistical inference because the likelihood function will be intractable for almost all partially observed stochastic processes. This renders many statistical methods, especially within a Bayesian framework, impossible to implement. Therefore, computationally expensive likelihood-free approaches are applied that replace likelihood evaluations with realisations of the model and observation process. For accurate inference, however, likelihood-free techniques may require millions of expensive stochastic simulations. To address this challenge, we develop a new method based on recent advances in multilevel and multifidelity. Our approach combines the multilevel Monte Carlo telescoping summation, applied to a sequence of approximate Bayesian posterior targets, with a multifidelity rejection sampler to minimise the number of computationally expensive exact simulations required for accurate inference. We present the derivation of our new algorithm for likelihood-free Bayesian inference, discuss practical implementation details, and demonstrate substantial performance improvements. Using examples from systems biology, we demonstrate improvements of more than two orders of magnitude over standard rejection sampling techniques. Our approach is generally applicable to accelerate other sampling schemes, such as sequential Monte Carlo, to enable feasible Bayesian analysis for realistic practical applications in physics, chemistry, biology, epidemiology, ecology and economics.

stat.CO↗

arXiv2022

Mean exit time in irregularly-shaped annular and composite disc domains

Calculating the mean exit time (MET) for models of diffusion is a classical problem in statistical physics, with various applications in biophysics, economics and heat and mass transfer. While many exact results for MET are known for diffusion in simple geometries involving homogeneous materials, calculating MET for diffusion in realistic geometries involving heterogeneous materials is typically limited to repeated stochastic simulations or numerical solutions of the associated boundary value problem (BVP). In this work we derive exact solutions for the MET in irregular annular domains, including some applications where diffusion occurs in heterogenous media. These solutions are obtained by taking the exact results for MET in an annulus, and then constructing various perturbation solutions to account for the irregular geometries involved. These solutions, with a range of boundary conditions, are implemented symbolically and compare very well with averaged data from repeated stochastic simulations and with numerical solutions of the associated BVP. Software to implement the exact solutions is available at https://github.com/ProfMJSimpson/Exit_time.

physics.bio-ph↗

arXiv2022

The Effect of Geometry on Survival and Extinction in a Moving-Boundary Problem Motivated by the Fisher-KPP Equation

The Fisher-Stefan model involves solving the Fisher-KPP equation on a domain whose boundary evolves according to a Stefan-like condition. The Fisher-Stefan model alleviates two practical limitations of the standard Fisher-KPP model when applied to biological invasion. First, unlike the Fisher-KPP equation, solutions to the Fisher-Stefan model have compact support, enabling one to define the interface between occupied and unoccupied regions unambiguously. Second, the Fisher-Stefan model admits solutions for which the population becomes extinct, which is not possible in the Fisher-KPP equation. Previous research showed that population survival or extinction in the Fisher-Stefan model depends on a critical length in one-dimensional Cartesian or radially-symmetric geometry. However, the survival and extinction behaviour for general two-dimensional regions remains unexplored. We combine analysis and level-set numerical simulations of the Fisher-Stefan model to investigate the survival-extinction conditions for rectangular-shaped initial conditions. We show that it is insufficient to generalise the critical length conditions to critical area in two-dimensions. Instead, knowledge of the region geometry is required to determine whether a population will survive or become extinct.

physics.bio-ph↗