arXiv subjects

Ruth E. Baker

Publications and source records attributed to Ruth E. Baker.

At least 55 records · Page 3Linked to original sources

arXiv2022

On the correspondence between symmetries of two-dimensional autonomous dynamical systems and their phase plane realisations

We consider the relationship between symmetries of two-dimensional autonomous dynamical system in two common formulations; as a set of differential equations for the derivative of each state with respect to time, and a single differential equation in the phase plane representing the dynamics restricted to the state space of the system. Both representations can be analysed with respect to the symmetries of their governing differential equations, and we establish the correspondence between the set of infinitesimal generators of the respective formulations. Our main result is to show that every generator of a symmetry of the autonomous system induces a well-defined vector field generating a symmetry in the phase plane and, conversely, that every symmetry generator in the phase plane can be lifted to a generator of a symmetry of the original autonomous system, which is unique up to constant translations in time. The process of lifting requires the solution of a linear partial differential equation, which we refer to as the lifting condition. We discuss in detail the solution of this equation in general, and exemplify the lift of symmetries in two commonly occurring examples; a mass conserved linear model and a non-linear oscillator model.

math.DS↗

arXiv2022

A local continuum model of cell-cell adhesion

Cell-cell adhesion is one the most fundamental mechanisms regulating collective cell migration during tissue development, homeostasis and repair, allowing cell populations to self-organize and eventually form and maintain complex tissue shapes. Cells interact with each other via the formation of protrusions or filopodia and they adhere to other cells through binding of cell surface proteins. The resulting adhesive forces are then related to cell size and shape and, often, continuum models represent them by nonlocal attractive interactions. In this paper, we present a new continuum model of cell-cell adhesion which can be derived from a general nonlocal model in the limit of short-range interactions. This new model is local, resembling a system of thin-film type equations, with the various model parameters playing the role of surface tensions between different cell populations. Numerical simulations in one and two dimensions reveal that the local model maintains the diversity of cell sorting patterns observed both in experiments and in previously used nonlocal models. In addition, it also has the advantage of having explicit stationary solutions, which provides a direct link between the model parameters and the differential adhesion hypothesis.

q-bio.CB↗

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

Control of diffusion-driven pattern formation behind a wave of competency

In certain biological contexts, such as the plumage patterns of birds and stripes on certain species of fishes, pattern formation takes place behind a so-called "wave of competency". Currently, the effects of a wave of competency on the patterning outcome is not well-understood. In this study, we use Turing's diffusion-driven instability model to study pattern formation behind a wave of competency, under a range of wave speeds. Numerical simulations show that in one spatial dimension a slower wave speed drives a sequence of peak splittings in the pattern, whereas a higher wave speed leads to peak insertions. In two spatial dimensions, we observe stripes that are either perpendicular or parallel to the moving boundary under slow or fast wave speeds, respectively. We argue that there is a correspondence between the one- and two-dimensional phenomena, and that pattern formation behind a wave of competency can account for the pattern organization observed in many biological systems.

q-bio.QM↗

arXiv2022

Symmetries of systems of first order ODEs: Symbolic symmetry computations, mechanistic model construction and applications in biology

We discuss the role and merits of symmetry methods for the analysis of biological systems. In particular, we consider systems of first order ordinary differential equations and provide a comprehensive review of the geometrical foundations pertinent to symmetries of such systems. Subsequently, we present an algorithm for finding infinitesimal generators of symmetries for systems with rational reaction terms, and an open-source implementation of the algorithm using symbolic computations. We discuss two complementary perspectives on symmetries in mechanistic modelling; as tools for the analysis of a given model or as a geometrical principle for incorporating biological properties in the construction of new models. Through numerous examples of relevance to modelling in biology we demonstrate the different uses of symmetry methods, and also discuss how to infer symmetries from experimental data.

q-bio.QM↗

arXiv2021

Measuring the accuracy of likelihood-free inference

Complex scientific models where the likelihood cannot be evaluated present a challenge for statistical inference. Over the past two decades, a wide range of algorithms have been proposed for learning parameters in computationally feasible ways, often under the heading of approximate Bayesian computation or likelihood-free inference. There is, however, no consensus on how to rigorously evaluate the performance of these algorithms. Here, we argue for scoring algorithms by the mean squared error in estimating expectations of functions with respect to the posterior. We show that score implies common alternatives, including the acceptance rate and effective sample size, as limiting special cases. We then derive asymptotically optimal distributions for choosing or sampling discrete or continuous simulation parameters, respectively. Our recommendations differ significantly from guidelines based on alternative scores outside of their region of validity. As an application, we show sequential Monte Carlo in this context can be made more accurate with no new samples by accepting particles from all rounds.

stat.CO↗

arXiv2021

Bayesian uncertainty quantification for data-driven equation learning

Equation learning aims to infer differential equation models from data. While a number of studies have shown that differential equation models can be successfully identified when the data are sufficiently detailed and corrupted with relatively small amounts of noise, the relationship between observation noise and uncertainty in the learned differential equation models remains unexplored. We demonstrate that for noisy data sets there exists great variation in both the structure of the learned differential equation models as well as the parameter values. We explore how to combine data sets to quantify uncertainty in the learned models, and at the same time draw mechanistic conclusions about the target differential equations. We generate noisy data using a stochastic agent-based model and combine equation learning methods with approximate Bayesian computation (ABC) to show that the correct differential equation model can be successfully learned from data, while a quantification of uncertainty is given by a posterior distribution in parameter space.

q-bio.QM↗

arXiv2021

Crowded transport within networked representations of complex geometries

Transport in crowded, complex environments occurs across many spatial scales. Geometric restrictions can hinder the motion of individuals and, combined with crowding between individuals, can have drastic effects on global transport phenomena. However, in general, the interplay between crowding and geometry in complex real-life environments is poorly understood. Existing analytical methodologies are not always readily extendable to heterogeneous environments: in these situations predictions of crowded transport behaviour within heterogeneous environments rely on computationally intensive mesh-based approaches. Here, we take a different approach by employing networked representations of complex environments to provide an efficient framework within which the interactions between networked geometry and crowding can be explored. We demonstrate how the framework can be used to: extract detailed information at the level of the whole population or an individual within it; identify the topological features of environments that enable accurate prediction of transport phenomena; and, provide insights into the design of optimal environments.

physics.soc-ph↗

arXiv2021

Learning differential equation models from stochastic agent-based model simulations

Agent-based models provide a flexible framework that is frequently used for modelling many biological systems, including cell migration, molecular dynamics, ecology, and epidemiology. Analysis of the model dynamics can be challenging due to their inherent stochasticity and heavy computational requirements. Common approaches to the analysis of agent-based models include extensive Monte Carlo simulation of the model or the derivation of coarse-grained differential equation models to predict the expected or averaged output from the agent-based model. Both of these approaches have limitations, however, as extensive computation of complex agent-based models may be infeasible, and coarse-grained differential equation models can fail to accurately describe model dynamics in certain parameter regimes. We propose that methods from the equation learning field provide a promising, novel, and unifying approach for agent-based model analysis. Equation learning is a recent field of research from data science that aims to infer differential equation models directly from data. We use this tutorial to review how methods from equation learning can be used to learn differential equation models from agent-based model simulations. We demonstrate that this framework is easy to use, requires few model simulations, and accurately predicts model dynamics in parameter regions where coarse-grained differential equation models fail to do so. We highlight these advantages through several case studies involving two agent-based models that are broadly applicable to biological phenomena: a birth-death-migration model commonly used to explore cell biology experiments and a susceptible-infected-recovered model of infectious disease spread.

math.DS↗

arXiv2021

Rapid Bayesian inference for expensive stochastic models

Almost all fields of science rely upon statistical inference to estimate unknown parameters in theoretical and computational models. While the performance of modern computer hardware continues to grow, the computational requirements for the simulation of models are growing even faster. This is largely due to the increase in model complexity, often including stochastic dynamics, that is necessary to describe and characterize phenomena observed using modern, high resolution, experimental techniques. Such models are rarely analytically tractable, meaning that extremely large numbers of stochastic simulations are required for parameter inference. In such cases, parameter inference can be practically impossible. In this work, we present new computational Bayesian techniques that accelerate inference for expensive stochastic models by using computationally inexpensive approximations to inform feasible regions in parameter space, and through learning transforms that adjust the biased approximate inferences to closer represent the correct inferences under the expensive stochastic model. Using topical examples from ecology and cell biology, we demonstrate a speed improvement of an order of magnitude without any loss in accuracy. This represents a substantial improvement over current state-of-the-art methods for Bayesian computations when appropriate model approximations are available.

stat.CO↗

arXiv2020

Multifidelity Approximate Bayesian Computation with Sequential Monte Carlo Parameter Sampling

Multifidelity approximate Bayesian computation (MF-ABC) is a likelihood-free technique for parameter inference that exploits model approximations to significantly increase the speed of ABC algorithms (Prescott and Baker, 2020). Previous work has considered MF-ABC only in the context of rejection sampling, which does not explore parameter space particularly efficiently. In this work, we integrate the multifidelity approach with the ABC sequential Monte Carlo (ABC-SMC) algorithm into a new MF-ABC-SMC algorithm. We show that the improvements generated by each of ABC-SMC and MF-ABC to the efficiency of generating Monte Carlo samples and estimates from the ABC posterior are amplified when the two techniques are used together.

stat.CO↗

arXiv2020

Biologically-informed neural networks guide mechanistic modeling from sparse experimental data

Biologically-informed neural networks (BINNs), an extension of physics-informed neural networks [1], are introduced and used to discover the underlying dynamics of biological systems from sparse experimental data. In the present work, BINNs are trained in a supervised learning framework to approximate in vitro cell biology assay experiments while respecting a generalized form of the governing reaction-diffusion partial differential equation (PDE). By allowing the diffusion and reaction terms to be multilayer perceptrons (MLPs), the nonlinear forms of these terms can be learned while simultaneously converging to the solution of the governing PDE. Further, the trained MLPs are used to guide the selection of biologically interpretable mechanistic forms of the PDE terms which provides new insights into the biological and physical mechanisms that govern the dynamics of the observed system. The method is evaluated on sparse real-world data from wound healing assays with varying initial cell densities [2].

q-bio.QM↗

arXiv2020

Efficiently simulating discrete-state models with binary decision trees

Stochastic simulation algorithms (SSAs) are widely used to numerically investigate the properties of stochastic, discrete-state models. The Gillespie Direct Method is the pre-eminent SSA, and is widely used to generate sample paths of so-called agent-based or individual-based models. However, the simplicity of the Gillespie Direct Method often renders it impractical where large-scale models are to be analysed in detail. In this work, we carefully modify the Gillespie Direct Method so that it uses a customised binary decision tree to trace out sample paths of the model of interest. We show that a decision tree can be constructed to exploit the specific features of the chosen model. Specifically, the events that underpin the model are placed in carefully-chosen leaves of the decision tree in order to minimise the work required to keep the tree up-to-date. The computational efficencies that we realise can provide the apparatus necessary for the investigation of large-scale, discrete-state models that would otherwise be intractable. Two case studies are presented to demonstrate the efficiency of the method.

q-bio.QM↗

arXiv2019

A practical guide to pseudo-marginal methods for computational inference in systems biology

For many stochastic models of interest in systems biology, such as those describing biochemical reaction networks, exact quantification of parameter uncertainty through statistical inference is intractable. Likelihood-free computational inference techniques enable parameter inference when the likelihood function for the model is intractable but the generation of many sample paths is feasible through stochastic simulation of the forward problem. The most common likelihood-free method in systems biology is approximate Bayesian computation that accepts parameters that result in low discrepancy between stochastic simulations and measured data. However, it can be difficult to assess how the accuracy of the resulting inferences are affected by the choice of acceptance threshold and discrepancy function. The pseudo-marginal approach is an alternative likelihood-free inference method that utilises a Monte Carlo estimate of the likelihood function. This approach has several advantages, particularly in the context of noisy, partially observed, time-course data typical in biochemical reaction network studies. Specifically, the pseudo-marginal approach facilitates exact inference and uncertainty quantification, and may be efficiently combined with particle filters for low variance, high-accuracy likelihood estimation. In this review, we provide a practical introduction to the pseudo-marginal approach using inference for biochemical reaction networks as a series of case studies. Implementations of key algorithms and examples are provided using the Julia programming language; a high performance, open source programming language for scientific computing.

q-bio.MN↗

arXiv2019

Effects of different discretisations of the Laplacian upon stochastic simulations of reaction-diffusion systems on both static and growing domains

By discretising space into compartments and letting system dynamics be governed by the reaction-diffusion master equation, it is possible to derive and simulate a stochastic model of reaction and diffusion on an arbitrary domain. However, there are many implementation choices involved in this process, such as the choice of discretisation and method of derivation of the diffusive jump rates, and it is not clear a priori how these affect model predictions. To shed light on this issue, in this work we explore how a variety of discretisations and method for derivation of the diffusive jump rates affect the outputs of stochastic simulations of reaction-diffusion models, in particular using Turing's model of pattern formation as a key example. We consider both static and uniformly growing domains and demonstrate that, while only minor differences are observed for simple reaction-diffusion systems, there can be vast differences in model predictions for systems that include complicated reaction kinetics, such as Turing's model of pattern formation. Our work highlights that care must be taken in using the reaction-diffusion master equation to make predictions as to the dynamics of stochastic reaction-diffusion systems.

physics.comp-ph↗

arXiv2019

Displacement of transport processes on networked topologies

Consider a particle whose position evolves along the edges of a network. One definition for the displacement of a particle is the length of the shortest path on the network between the current and initial positions of the particle. Such a definition fails to incorporate information of the actual path the particle traversed. In this work we consider another definition for the displacement of a particle on networked topologies. Using this definition, which we term the winding distance, we demonstrate that for Brownian particles, confinement to a network can induce a transition in the mean squared displacement from diffusive to ballistic behaviour, $\langle x^2(t) \rangle \propto t^2$ for long times. A multiple scales approach is used to derive a macroscopic evolution equation for the displacement of a particle and uncover a topological condition for whether this transition in the mean squared displacement will occur. Furthermore, for networks satisfying this topological condition, we identify a prediction of the timescale upon which the displacement transitions to long-time behaviour. Finally, we extend the investigation of displacement on networks to a class of anomalously diffusive transport processes, where we find that the mean squared displacement at long times is affected by both network topology and the character of the transport process.

cond-mat.stat-mech↗

arXiv2019

Convergence of solutions in a mean-field model of go-or-grow type with reservation of sites for proliferation and cell cycle delay

We consider the mean-field approximation of an individual-based model describing cell motility and proliferation, which incorporates the volume exclusion principle, the go-or-grow hypothesis and an explicit cell cycle delay. To utilise the framework of on-lattice agent-based models, we make the assumption that cells enter mitosis only if they can secure an additional site for the daughter cell, in which case they occupy two lattice sites until the completion of mitosis. The mean-field model is expressed by a system of delay differential equations and includes variables such as the number of motile cells, proliferating cells, reserved sites and empty sites. We prove the convergence of biologically feasible solutions: eventually all available space will be filled by mobile cells, after an initial phase when the proliferating cell population is increasing then diminishing. By comparing the behaviour of the mean-field model for different parameter values and initial cell distributions, we illustrate that the total cell population may follow a logistic-type growth curve, or may grow in a step-function-like fashion.

q-bio.CB↗

arXiv2019

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.

q-bio.MN↗