Enhancing generalizability of model discovery across parameter space with multi-experiment equation learning for biological systems

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: (i) one-at-a-time ME-EQL (OAT ME-EQL), which learns individual models for each parameter set and connects them via interpolation, and (ii) embedded structure ME-EQL (ES ME-EQL), which builds a unified model library across parameters. We demonstrate these methods by learning continuum models from a noisy birth-death mean-field model and from an on-lattice agent-based model of birth, death, and migration with spatial structure, often used to investigate cell biology experiments. We 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.

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Publication Details

Journal
PLoS Computational Biology
Published
2026-04-22
DOI
https://doi.org/10.1371/journal.pcbi.1014161
Primary Topic
Mathematical Biology Tumor Growth
Type
article
Field-Weighted Citation Impact
0.00

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article

Enhancing generalizability of model discovery across parameter space with multi-experiment equation learning for biological systems

Alexandria Volkening, John T. Nardini, Suzanne Sindi, Kevin Flores et al.
PLoS Computational Biology
Mathematical Biology Tumor Growth
article

Enhancing generalizability of model discovery across parameter space with multi-experiment equation learning for biological systems

Alexandria Volkening, John T. Nardini, Suzanne Sindi, Kevin Flores, Maria-Veronica Ciocanel, Erica M. Rutter
article en

Abstract

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: (i) one-at-a-time ME-EQL (OAT ME-EQL), which learns individual models for each parameter set and connects them via interpolation, and (ii) embedded structure ME-EQL (ES ME-EQL), which builds a unified model library across parameters. We demonstrate these methods by learning continuum models from a noisy birth-death mean-field model and from an on-lattice agent-based model of birth, death, and migration with spatial structure, often used to investigate cell biology experiments. We 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.

PLoS Computational BiologyVol. 22(4)
North Carolina State University (US), University of California, Merced (US), Duke University (US), Purdue University West Lafayette (US), The College of New Jersey (US)
National Science Foundation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Reduced inequalities
Openalex Percentile: Top 18%
Mathematical Biology Tumor Growth
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