arXiv subjects

John T. Nardini

Publications and source records attributed to John T. Nardini.

15 recordsLinked to original sources

arXiv2026

Spatial Model Selection and Uncertainty Quantification: Comparing Continuous and Discrete Wound Healing Models

All data-driven modeling tasks (e.g., parameter estimation, uncertainty quantification, and data forecasting) require the selection of a mathematical model. An overlooked aspect of model selection is modality; for example, there are no guidelines on when to use a partial differential equation (PDE) model or an agent-based model (ABM) for spatial processes. To address this, we created a model selection pipeline that uses approximate Bayesian computations to perform parameter estimation, uncertainty quantification, and model selection (using both information criteria and out-of-sample forecasting). Applying the pipeline to artificial datasets (generated from ABMs) reveals that while both modalities yield comparable parameter estimation performance, the ABM estimates exhibit higher uncertainty, and the PDE models compute more than 1,000$\times$ faster. Surprisingly, the mean-field PDE is often selected over the true generative ABM model using both information criteria and data forecasting. Applying the pipeline to public wound healing data indicates that a PDE model with cell pulling and a time delay is the most appropriate model for this data, however, this model has high levels of parametric uncertainty. This methodology establishes a preliminary framework for selecting the appropriate modeling modality for spatial biological data.

q-bio.QM↗

arXiv2026

Physics-Informed Neural Networks for Biological $2\mathrm{D}{+}t$ Reaction-Diffusion Systems

Physics-informed neural networks (PINNs) provide a powerful framework for learning governing equations of dynamical systems from data. Biologically-informed neural networks (BINNs) are a variant of PINNs that preserve the known differential operator structure (e.g., reaction-diffusion) while learning constitutive terms via trainable neural subnetworks, enforced through soft residual penalties. Existing BINN studies are limited to $1\mathrm{D}{+}t$ reaction-diffusion systems and focus on forward prediction, using the governing partial differential equation as a regulariser rather than an explicit identification target. Here, we extend BINNs to $2\mathrm{D}{+}t$ systems within a PINN framework that combines data preprocessing, BINN-based equation learning, and symbolic regression post-processing for closed-form equation discovery. We demonstrate the framework's real-world applicability by learning the governing equations of lung cancer cell population dynamics from time-lapse microscopy data, recovering $2\mathrm{D}{+}t$ reaction-diffusion models from experimental observations. The proposed framework is readily applicable to other spatio-temporal systems, providing a practical and interpretable tool for fast analytic equation discovery from data.

cs.LG↗

arXiv2026

Enhancing generalizability of model discovery across parameter space with multi-experiment equation learning (ME-EQL)

Agent-based modeling (ABM) is a powerful tool for understanding self-organizing biological systems, but it is computationally intensive and often not analytically tractable. Equation learning (EQL) methods can derive continuum models from ABM data, but they typically require extensive simulations for each parameter set, raising concerns about generalizability. In this work, we extend EQL to Multi-experiment equation learning (ME-EQL) by introducing two methods: one-at-a-time ME-EQL (OAT ME-EQL), which learns individual models for each parameter set and connects them via interpolation, and embedded structure ME-EQL (ES ME-EQL), which builds a unified model library across parameters. We demonstrate these methods using a birth--death mean-field model and an on-lattice agent-based model of birth, death, and migration with spatial structure. Our results show that both methods significantly reduce the relative error in recovering parameters from agent-based simulations, with OAT ME-EQL offering better generalizability across parameter space. Our findings highlight the potential of equation learning from multiple experiments to enhance the generalizability and interpretability of learned models for complex biological systems.

cs.LG↗

arXiv2025

SSRCA: a novel machine learning pipeline to perform sensitivity analysis for agent-based models

Agent-based models (ABMs) are widely used in biology to understand how individual actions scale into emergent population behavior. Modelers employ sensitivity analysis (SA) algorithms to quantify input parameters' impact on model outputs, however, it is hard to perform SA for ABMs due to their computational and complex nature. In this work, we develop the Simulate, Summarize, Reduce, Cluster, and Analyze (SSRCA) methodology, a machine-learning based pipeline designed to facilitate SA for ABMs. In particular, SSRCA can achieve the following tasks for ABMS: 1) identify sensitive model parameters, 2) reveal common output model patterns, and 3) determine which input parameter values generate these patterns. We use an example ABM of tumor spheroid growth to showcase how SSRCA identifies four common patterns from the ABM and the parameter regions that generate these outputs. Additionally, we compare the SA results between SSRCA and the popular Sobol' Method and find that SSRCA's identified sensitive parameters are robust to the choice of model descriptors while Sobol's are not. This analysis could streamline data-driven tasks, such as parameter estimation, for ABMs by reducing parameter space. While we highlight these results with an ABM on tumor spheroid formation, the SSRCA Methodology is broadly applicable to biological ABMs.

q-bio.QM↗

arXiv2024

Forecasting and predicting stochastic agent-based model data with biologically-informed neural networks

Collective migration is an important component of many biological processes, including wound healing, tumorigenesis, and embryo development. Spatial agent-based models (ABMs) are often used to model collective migration, but it is challenging to thoroughly predict these models' behavior throughout parameter space due to their random and computationally intensive nature. Modelers often coarse-grain ABM rules into mean-field differential equation (DE) models. While these DE models are fast to simulate, they suffer from poor (or even ill-posed) ABM predictions in some regions of parameter space. In this work, we describe how biologically-informed neural networks (BINNs) can be trained to learn interpretable BINN-guided DE models capable of accurately predicting ABM behavior. In particular, we show that BINN-guided partial DE (PDE) simulations can 1.) forecast future spatial ABM data not seen during model training, and 2.) predict ABM data at previously-unexplored parameter values. This latter task is achieved by combining BINN-guided PDE simulations with multivariate interpolation. We demonstrate our approach using three case study ABMs of collective migration that imitate cell biology experiments and find that BINN-guided PDEs accurately forecast and predict ABM data with a one-compartment PDE when the mean-field PDE is ill-posed or requires two compartments. This work suggests that BINN-guided PDEs allow modelers to efficiently explore parameter space, which may enable data-driven tasks for ABMs, such as estimating parameters from experimental data. All code and data from our study is available at https://github.com/johnnardini/Forecasting_predicting_ABMs.

q-bio.QM↗

arXiv2022

Statistical and Topological Summaries Aid Disease Detection for Segmented Retinal Vascular Images

Disease complications can alter vascular network morphology and disrupt tissue functioning. Diabetic retinopathy, for example, is a complication of types 1 and 2 diabetes mellitus that can cause blindness. Microvascular diseases are assessed by visual inspection of retinal images, but this can be challenging when diseases exhibit silent symptoms or patients cannot attend in-person meetings. We examine the performance of machine learning algorithms in detecting microvascular disease when trained on statistical and topological summaries of segmented retinal vascular images. We apply our methods to three publicly-available datasets and find that, among the 13 total descriptor vectors we consider, either a statistical Box-counting descriptor vector or a topological Flooding descriptor vector achieves the highest accuracy levels on these datasets. We then created a fourth dataset by merging several datasets: the Box-counting vector outperforms all descriptors on this dataset, including the topological Flooding vector which is sensitive to differences in the annotation styles within the combined dataset. Our work represents a first step to establishing which computational methods are most suitable for identifying microvascular disease as well as some of their current limitations. In the longer term, these methods could be incorporated into automated disease assessment tools.

q-bio.QM↗

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

Topological data analysis distinguishes parameter regimes in the Anderson-Chaplain model of angiogenesis

Angiogenesis is the process by which blood vessels form from pre-existing vessels. It plays a key role in many biological processes, including embryonic development and wound healing, and contributes to many diseases including cancer and rheumatoid arthritis. The structure of the resulting vessel networks determines their ability to deliver nutrients and remove waste products from biological tissues. Here we simulate the Anderson-Chaplain model of angiogenesis at different parameter values and quantify the vessel architectures of the resulting synthetic data. Specifically, we propose a topological data analysis (TDA) pipeline for systematic analysis of the model. TDA is a vibrant and relatively new field of computational mathematics for studying the shape of data. We compute topological and standard descriptors of model simulations generated by different parameter values. We show that TDA of model simulation data stratifies parameter space into regions with similar vessel morphology. The methodologies proposed here are widely applicable to other synthetic and experimental data including wound healing, development, and plant biology.

q-bio.QM↗

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

Learning Equations from Biological Data with Limited Time Samples

Equation learning methods present a promising tool to aid scientists in the modeling process for biological data. Previous equation learning studies have demonstrated that these methods can infer models from rich datasets, however, the performance of these methods in the presence of common challenges from biological data has not been thoroughly explored. We present an equation learning methodology comprised of data denoising, equation learning, model selection and post-processing steps that infers a dynamical systems model from noisy spatiotemporal data. The performance of this methodology is thoroughly investigated in the face of several common challenges presented by biological data, namely, sparse data sampling, large noise levels, and heterogeneity between datasets. We find that this methodology can accurately infer the correct underlying equation and predict unobserved system dynamics from a small number of time samples when the data is sampled over a time interval exhibiting both linear and nonlinear dynamics. Our findings suggest that equation learning methods can be used for model discovery and selection in many areas of biology when an informative dataset is used. We focus on glioblastoma multiforme modeling as a case study in this work to highlight how these results are informative for data-driven modeling-based tumor invasion predictions.

q-bio.QM↗

arXiv2020

Analyzing Collective Motion with Machine Learning and Topology

We use topological data analysis and machine learning to study a seminal model of collective motion in biology [D'Orsogna et al., Phys. Rev. Lett. 96 (2006)]. This model describes agents interacting nonlinearly via attractive-repulsive social forces and gives rise to collective behaviors such as flocking and milling. To classify the emergent collective motion in a large library of numerical simulations and to recover model parameters from the simulation data, we apply machine learning techniques to two different types of input. First, we input time series of order parameters traditionally used in studies of collective motion. Second, we input measures based in topology that summarize the time-varying persistent homology of simulation data over multiple scales. This topological approach does not require prior knowledge of the expected patterns. For both unsupervised and supervised machine learning methods, the topological approach outperforms the one that is based on traditional order parameters.

math.AT↗

arXiv2019

Learning partial differential equations for biological transport models from noisy spatiotemporal data

We investigate methods for learning partial differential equation (PDE) models from spatiotemporal data under biologically realistic levels and forms of noise. Recent progress in learning PDEs from data have used sparse regression to select candidate terms from a denoised set of data, including approximated partial derivatives. We analyze the performance in utilizing previous methods to denoise data for the task of discovering the governing system of partial differential equations (PDEs). We also develop a novel methodology that uses artificial neural networks (ANNs) to denoise data and approximate partial derivatives. We test the methodology on three PDE models for biological transport, i.e., the advection-diffusion, classical Fisher-KPP, and nonlinear Fisher-KPP equations. We show that the ANN methodology outperforms previous denoising methods, including finite differences and polynomial regression splines, in the ability to accurately approximate partial derivatives and learn the correct PDE model.

math.DS↗

arXiv2018

The Influence of Numerical Error on an Inverse Problem Methodology in PDE Models

The inverse problem methodology is a commonly-used framework in the sciences for parameter estimation and inference. It is typically performed by fitting a mathematical model to noisy experimental data. There are two significant sources of error in the process: 1.\ Noise from the measurement and collection of experimental data and 2.\ numerical error in approximating the true solution to the mathematical model. Little attention has been paid to how this second source of error alters the results of an inverse problem. As a first step towards a better understanding of this problem, we present a modeling and simulation study using a simple advection-driven PDE model. We present both analytical and computational results concerning how the different sources of error impact the least squares cost function as well as parameter estimation and uncertainty quantification. We investigate residual patterns to derive an autocorrelative statistical model that can improve parameter estimation and confidence interval computation for first order methods. Building on the results of our investigation, we provide guidelines for practitioners to determine when numerical or experimental error is the main source of error in their inference, along with suggestions of how to efficiently improve their results.

math.NA↗

arXiv2016

Investigation of a Structured Fisher's Equation with Applications in Biochemistry

Recent biological research has sought to understand how biochemical signaling pathways, such as the mitogen-activated protein kinase (MAPK) family, influence the migration of a population of cells during wound healing. Fisher's Equation has been used extensively to model experimental wound healing assays due to its simple nature and known traveling wave solutions. This partial differential equation with independent variables of time and space cannot account for the effects of biochemical activity on wound healing, however. To this end, we derive a structured Fisher's Equation with independent variables of time, space, and biochemical pathway activity level and prove the existence of a self-similar traveling wave solution to this equation. We also consider a more complicated model with different phenotypes based on MAPK activation and numerically investigate how various temporal patterns of biochemical activity can lead to increased and decreased rates of population migration.

math.AP↗

arXiv2015

The effects of MAPK activity on cell-cell adhesion during wound healing

The mechanisms underlying collective migration, or the coordinated movement of a population of cells, are not well understood despite its ubiquitous nature. As a means to investigate collective migration, we consider a wound healing scenario in which a population of cells fills in the empty space left from a scratch wound. Here we present a simplified mathematical model that uses reaction-diffusion equations to model collective migration during wound healing with an emphasis on cell movement and its response to both cell signaling and cell-cell adhesion. We use the model to investigate the effect of the MAPK signaling cascade on cell-cell adhesion during wound healing after EGF treatment. Our results suggest that activation of the MAPK signaling cascade stimulates collective migration through increases in the pulling strength of leader cells. We further use the model to suggest that treating a cell population with EGF converts the time to wound closure (as function of wound area) from parabolic to linear.

q-bio.CB↗