Biology subjects

Drovandi, C.

Publications and source records attributed to Drovandi, C..

10 recordsLinked to original sources

bioRxiv2026

Bayesian Parameter Balancing Enables Robust and Consistent Estimation of Kinetic Parameter Uncertainty

MotivationKinetic models are central to systems biology, but enzyme-kinetic parameters compiled from the literature and databases are often incomplete, inconsistent, and measured under heterogeneous conditions. Classical parameter balancing helps infer missing parameters, yet it often lacks calibrated uncertainty, robustness to misspecification, and explicit treatment of source-level heterogeneity. ResultsWe develop a formal Bayesian parameter balancing framework that enforces thermodynamic constraints, estimates full posterior uncertainty, and validates calibration using leave-one-out cross-validation and posterior-predictive coverage. Beyond the classical Gaussian formulation, we introduce robust Student-t and skewed error models to improve reliability under outliers and model misspecification, and incorporate random effects to account for source-level or group-level variability across studies. The resulting approach yields thermodynamically consistent parameter sets with well-calibrated credible intervals on held-out data, offering a Bayesian parameter balancing approach useful to systems biology researchers. Availability and implementationSource code, data, workflows, a Julia package and command-line usage are available at the project GitHub repository. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/726043v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@182b3c2org.highwire.dtl.DTLVardef@1e79bdforg.highwire.dtl.DTLVardef@aa56a7org.highwire.dtl.DTLVardef@11f2de2_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

Predicting animal movement with deepSSF: a deep learning step selection framework

O_LIPredictions of animal movement are vital for understanding and managing wild populations. However, the fine-scale, complex decision-making of animals can pose challenges for the accurate prediction of trajectories. Step selection functions (SSFs), a common tool for inferring relationships between animal movement and the environment, are also increasingly used to simulate animal trajectories for prediction. Although admitting a lot of flexibility, the SSF framework is limited to its reliance on pre-defined functional forms for fitting to data, and SSFs that involve complex functional forms to model detailed processes can be prohibitively difficult to fit and interpret. C_LIO_LIHere, we present deepSSF, an approach to fit and predict animal movement data using deep learning. Whilst not specific to any particular model, we denote the deepSSF approach as building and training a neural network architecture that receives multiple environmental layers and scalar values as inputs, and outputs a single layer representing the next-step probability. To demonstrate a deepSSF model, we build a model in PyTorch that has distinct but interacting habitat selection and movement subnetworks, which allows for explicit representation of both processes and interpretable intermediate outputs. We apply our model to GPS data of introduced water buffalo (Bubalus bubalis) in the tropical savannas of Northern Australia. C_LIO_LIOur deepSSF model was able to learn features that are present in the habitat covariate layers, such as linear features (rivers, forest edges), and the composition of certain habitat areas, without having to specify them pre-emptively within the SSF framework. It was also able to capture the complex interactions between the habitat covariates as well as temporal dynamics across time of day and year. C_LIO_LIWe expect that the deepSSF approach will generate accurate and informative animal movement trajectories, which can be used for deepening our understanding of animal-environment systems and for the practical management of species. Considering the wide range of deep learning tools, the deepSSF approach could be extended to represent memory and social dynamic processes, with the potential for integrating non-spatial data sources such as accelerometers and physiological sensors. C_LI

ecology↗

bioRxiv2024

EEMtoolbox: A user-friendly R package for flexible ensemble ecosystem modeling

O_LIForecasting ecosystem changes due to disturbances or conservation interventions is essential to improve ecosystem management and anticipate unintended consequences of conservation decisions. Mathematical models allow practitioners to understand the potential effects and unintended consequences via simulation. However, calibrating these models is often challenging due to a paucity of appropriate ecological data. C_LIO_LIEnsemble ecosystem modelling (EEM) is a quantitative method used to parameterize models from theoretical ecosystem features rather than data. Two approaches have been considered to find parameter values satisfying those features: a standard accept-reject algorithm, appropriate for small ecosystem networks; and a sequential Monte Carlo (SMC) algorithm, that is more computationally efficient for larger networks. In practice, using SMC for EEM generation requires advanced statistical and mathematical knowledge, as well as strong programming skills, which might limit its uptake. In addition, current EEM approaches have been developed for only one model structure (generalized Lotka-Volterra). C_LIO_LITo facilitate the usage of EEM methods we introduce EEMtoolbox, an R package for calibrating quantitative ecosystem models. Our package allows the generation of parameter sets satisfying ecosystem features, by using either the standard accept-reject algorithm or the novel SMC procedure. Our package extends the existing EEM methodology, originally developed for the generalized Lotka-Volterra model, to two additional model structures (the multi-species Gompertz, and the Bimler-Baker model), and additionally allows users to define their own model structures. C_LIO_LIWe demonstrate the usage of EEMtoolbox by modelling the introduction of sihek (extinct-in-the-wild) on Palmyra Atoll in the Pacific Ocean. With its simple interface, our package facilitates straightforward generation of EEM parameter sets, thus unlocks advanced statistical methods supporting conservation decisions using ecosystem network models. C_LI

ecology↗

bioRxiv2024

Simulating animal movement trajectories from temporally dynamic step selection functions

Understanding and predicting animal movement is fundamental to ecology and conservation management. Models that estimate and then predict animal movement and habitat selection parameters underpin diverse conservation applications, from mitigating invasive species spread to enhancing landscape connectivity. However, many predictive models overlook fine-scale temporal dynamics within their predictions, despite animals often displaying fine-scale behavioural variability that might significantly alter their movement, habitat selection and distribution over time. Incorporating fine-scale temporal dynamics, such as circadian rhythms, within predictive models might reduce the averaging out of such behaviours, thereby enhancing our ability to make predictions in both the short and long term. We tested whether the inclusion of fine-scale temporal dynamics improved both fine-scale (hourly) and long-term (seasonal) spatial predictions for a significant invasive species of Northern Australia, the water buffalo (Bubalus bubalis). Water buffalo require intensive management actions over vast, remote areas and display distinct circadian rhythms linked to habitat use. To inform management operations we generated hourly and dry season prediction maps by simulating trajectories from static and temporally dynamic step selection functions (SSFs) that were fitted to the GPS data of 13 water buffalo. We found that simulations generated from temporally dynamic models replicated the buffalos crepuscular movement patterns and dynamic habitat selection, resulting in more informative and accurate hourly predictions. Additionally, when the simulations were aggregated into long-term predictions, the dynamic models were more accurate and better able to highlight areas of concentrated habitat use that might indicate high-risk areas for environmental damage. Our findings emphasise the importance of incorporating fine-scale temporal dynamics in predictive models for species with clear dynamic behavioural patterns. By integrating temporally dynamic processes into animal movement trajectories, we demonstrate an approach that can enhance conservation management strategies and deepen our understanding of ecological and behavioural patterns across multiple timescales.

ecology↗

bioRxiv2022

Calibration of a Voronoi cell-based model for tumour growth using approximate Bayesian computation

Agent-based models (ABMs) are readily used to capture the stochasticity in tumour evolution; however, these models are often challenging to validate with experimental measurements due to model complexity. The Voronoi cell-based model (VCBM) is an off-lattice agent-based model that captures individual cell shapes using a Voronoi tessellation and mimics the evolution of cancer cell proliferation and movement. Evidence suggests tumours can exhibit biphasic growth in vivo. To account for this phenomena, we extend the VCBM to capture the existence of two distinct growth phases. Prior work primarily focused on point estimation for the parameters without consideration of estimating uncertainty. In this paper, approximate Bayesian computation is employed to calibrate the model to in vivo measurements of breast, ovarian and pancreatic cancer. Our approach involves estimating the distribution of parameters that govern cancer cell proliferation and recovering outputs that match the experimental data. Our results show that the VCBM, and its biphasic extension, provides insight into tumour growth and quantifies uncertainty in the switching time between the two phases of the biphasic growth model. We find this approach enables precise estimates for the time taken for a daughter cell to become a mature cell. This allows us to propose future refinements to the model to improve accuracy, whilst also making conclusions about the differences in cancer cell characteristics.

systems biology↗

bioRxiv2022

Computationally efficient mechanism discovery for cell invasion with uncertainty quantification

Parameter estimation for mathematical models of biological processes is often difficult and depends significantly on the quality and quantity of available data. We introduce an efficient frame-work using Gaussian processes to discover mechanisms underlying delay, migration, and proliferation in a cell invasion experiment. Gaussian processes are leveraged with bootstrapping to provide uncertainty quantification for the mechanisms that drive the invasion process. Our frame-work is efficient, parallelisable, and can be applied to other biological problems. We illustrate our methods using a canonical scratch assay experiment, demonstrating how simply we can explore different functional forms and develop and test hypotheses about underlying mechanisms, such as whether delay is present. All code and data to reproduce this work are available at https://github.com/DanielVandH/EquationLearning.jl. 1 Author summaryIn this work we introduce uncertainty quantification into equation learning methods, such as physics-informed and biologically-informed neural networks. Our framework is computationally efficient and applicable to problems with unknown nonlinear mechanisms that we wish to learn from experiments where only sparse noisy data are available. We demonstrate our methods on a canonical scratch assay experiment from cell biology and show the underlying mechanisms can be learned, providing confidence intervals for functional forms and for solutions to partial differential equation models believed to describe the experiment.

cell biology↗

bioRxiv2021

Identifying cell-to-cell variability in internalisation using flow cytometry

Biological heterogeneity is a primary contributor to the variation observed in experiments that probe dynamical processes, such as internalisation. Given that internalisation is a critical process by which many therapeutics and viruses reach their intracellular site of action, quantifying cell-to-cell variability in internalisation is of high biological interest. Yet, it is common for studies of internalisation to neglect cell-to-cell variability. We develop a simple mathematical model of internalisation that captures the dynamical behaviour, cell-to-cell variation, and extrinsic noise introduced by flow cytometry. We calibrate our model through a novel distribution-matching approximate Bayesian computation algorithm to flow cytometry data of internalisation of anti-transferrin receptor antibody in a human B-cell lymphoblastoid cell line. Our model reproduces experimental observations, identifies cell-to-cell variability in the internalisation and recycling rates, and, importantly, provides information relating to inferential uncertainty. Given that our approach is agnostic to sample size and signal-to-noise ratio, our modelling framework is broadly applicable to identify biological variability in single-cell data from internalisation assays and similar experiments that probe cellular dynamical processes.

cell biology↗

bioRxiv2021

Estimating parameters of a stochastic cell invasion model with fluorescent cell cycle labelling using Approximate Bayesian Computation

We develop a parameter estimation method based on approximate Bayesian computation (ABC) for a stochastic cell invasion model using fluorescent cell cycle labeling with proliferation, migration, and crowding effects. Previously, inference has been performed on a deterministic version of the model fitted to cell density data, and not all the parameters were identifiable. Considering the stochastic model allows us to harness more features of experimental data, including cell trajectories and cell count data, which we show overcomes the parameter identifiability problem. We demonstrate that, whilst difficult to collect, cell trajectory data can provide more information about the parameters of the cell invasion model. To handle the intractability of the likelihood function of the stochastic model, we use an efficient ABC algorithm based on sequential Monte Carlo. Rcpp and MATLAB implementations of the simulation model and ABC algorithm used in this study are available at https://github.com/michaelcarr-stats/FUCCI.

cell biology↗

bioRxiv2020

Minimising severity of dengue serotype 1 infection bytransmissible interfering particles

Transmissible interfering dengue particles (DENV-TIPs) are engineered dengue virus mutants which are defective and can replicate only with the help of dengue wild-type virus (DENV). In vitro studies have found that when DENV-TIPs and DENV coinfect a cell, they compete for viral genomes and cell proteins for replication and packaging, and DENV-TIPs outperform DENV in this process. Thus, it is hypothesised that DENV-TIPs may be used as a novel therapeutic agent. However, the effectiveness of DENV-TIPs as an antiviral agent is yet to be explored at an epidemiological scale. We present a mathematical model for the replication of DENV and DENV-TIPs as they interact with human host cells, accounting for the effectiveness of DENV-TIPs in blocking DENV from coinfected cells. We fit the model to sequentially measured plasma viral titre data from primary and secondary dengue serotype 1 infected patients in Vietnam. We show that variation in initial DENV load is sufficient to recreate the observed variation between patients. Parameter estimates, differing in primary and secondary infections, do not confirm a significant difference between these two types of infection. We use our model to investigate the potential impact of DENV-TIPs as an antiviral agent. We conclude that, when the effectiveness of DENV-TIPs in inhibiting DENV from coinfected cells is at least 80%, a dose as high as 1012 copies per millilitre of blood is required to reduce duration of infection and peak DENV serotype 1 infection level at any time point of infection. This work provides a quantitative understanding of the relationship between DENV-TIPs levels and their efficiency in clearing dengue viral infection. It will guide future development of mechanistic models of how DENV-TIPs might contribute as an antiviral agent in limiting natural dengue infection. Author summaryInhibition of dengue wild-type virus (DENV) by transmissible interfering dengue particles (DENV-TIPs) is seen in some in vitro studies, and it is hypothesised that DENV-TIPs may be used as a therapeutic agent. However, the efficiency of DENV-TIPs in limiting DENV infection in patients is yet to be explored at an epidemiological scale. Using data collected from dengue serotype 1 infected patients, we model how DENV replicates in an infected patient and how effective DENV-TIPs are in controlling that replication. Our results are of use in the evaluation of DENV-TIPs as a potential antiviral agent.

developmental biology↗

bioRxiv2019

Estimating a novel stochastic model for within-field disease dynamics of banana bunchy top virus via approximate Bayesian computation

The Banana Bunchy Top Virus (BBTV) is one of the most economically important vector-borne banana diseases throughout the Asia-Pacific Basin and presents a significant challenge to the agricultural sector. Current models of BBTV are largely deterministic, limited by an incomplete understanding of interactions in complex natural systems, and the appropriate identification of parameters. A stochastic network-based Susceptible-Infected model has been created which simulates the spread of BBTV across the subsections of a banana plantation, parameterising nodal recovery, neighbouring and distant infectivity across summer and winter. Findings from posterior results achieved through Markov Chain Monte Carlo approach to approximate Bayesian computation suggest seasonality in all parameters, which are influenced by correlated changes in inspection accuracy, temperatures and aphid activity. This paper demonstrates how the model may be used for monitoring and forecasting of various disease management strategies to support policy-level decision making.\n\nAuthor summaryThe Banana Bunchy Top Virus (BBTV) poses one of the greatest threats to the food security of developing nations and the banana industry throughout the Asia-Pacific Basin. Decision-makers face significant challenges in mitigating BBTV spread in banana plantations due to the vector-borne spread of this disease, which is significantly influenced by a vast array of external environmental factors that are unique to each plantation.\n\nWe propose a flexible network-based model that describes the spread of BBTV in a real banana plantation through a random process while accounting for individual plantation characteristics and utilise a principled methodology for estimating model parameters. Our findings quantify the effect of seasonal changes and plantation configuration on BBTV spread and predict for high-risk areas in this plantation. We believe that our model might be used by decision-makers to evaluate the effectiveness of current disease management strategies and explore opportunities for improvements.

systems biology↗