MS08 - MFBM-14

Multicellular Agent-Based Modelling - The OpenVT Project (Part 3)

Friday, July 18 at 10:20am

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Note: this minisymposia has multiple sessions. The other sessions are: Part-1, and Part-2.

James Osborne (University of Melbourne), James Glazier (Indiana University) Yi Jiang (Georgia State University)

Description:

Multicellular simulations have become indispensable in understanding complex biological phenomena, from tissue development to disease progression. But the diversity in simulation methods - from agent-based models, lattice-free models, stochastic particle simulations, etc - poses challenges in reproducibility, modularity, reusability, and integration within multi-scale simulation. This minisymposia aims to present the variety of multicellular simulations being used by the community along with the efforts to make these simulations replicable and reproducible. Through a series of scientific presentations, we will demonstrate the need for standardization, and the importance of sharing and reusing models. The minisymposia is broken up into three parts; Parts 1 and 2: Modelling Biological Systems 1 and 2. Part 3: Reproducibility and Standards. Parts 1 and 2 of the Minisymposia (Modelling Biological Systems 1 and 2) contain a series of scientifically focused talks to demonstrate the variety of modelling techniques and applications being used in multicellular simulations. These talks have a scientific focus however each talk will have 5 minutes dedicated to model specification/reproducibility/comparison. Part 3 of the Minisymposia (Reproducibility and Standards) contains a series of talks on the current efforts in reproducibility and standards for multicellular simulations including a report on the OpenVT Satellite meeting reproducibility challenge.

James Glazier

Indiana University, USA

"OpenVT--Towards Making Virtual Tissue Models FAIR - Opportunities and Challenges"

Multi-scale, Multicellular Agent-Based Virtual-Tissue models built using modeling frameworks like CompuCell3D, Morpheus, Artistoo, CHASTE or PhysiCell are versatile tools for exploring the complex interactions between intracellular signaling and gene-regulatory networks, inter-cellular signaling through contact and diffusible signals, and force generation, cell migration and shape change. They can play a crucial role in helping to interpret and design more informative experiments, in particular in in vitro to in vivo extrapolation. However, Virtual Tissues currently lack the model-specification standards, support for modular architectures and annotation, cross-compatible tools for graphical model specification, visualization and analysis and accepted model sharing infrastructure that have enabled the rapid developing of systems biology network modeling as a core technology in modern biology and the regulatory acceptance of these approaches. Comparable infrastructure is essential for Virtual Tissues to move from academic one-offs for discovery science to truly progressive mainstream technologies in biomedicine, technology and regulation. Because Virtual Tissues are substantially more complex and structurally and functionally diverse than network models, standardization and modularization, graphical specification and distribution are all more challenging. I will consider some of the variety of Virtual Tissue applications, frameworks and modeling approaches and some of the challenges and opportunities we face in developing an effective ecosystem of tools and standards. I will also discuss how the NSF-funded OpenVT project is working to build community to address these challenges.

TJ Sego

University of Florida, USA

"Quantitative Reproducibility at Scale: A Federated, Standardizable Approach"

Stochastic simulations are commonly used to quantitatively or semi-quantitatively describe the dynamics of biological systems. Proving reproducibility of simulation results is critical to establishing the credibility of a model. However, reproducibility of stochastic simulation is difficult for numerous reasons. For example, under-sampling produces insufficient information to allow conclusive findings from independent reproducibility studies. Hence, along with measures to compare results, reproducible stochastic simulation as a community-level practice requires measures of when results can be verified as meaningfully reproduced in independent study, and data formats for facilitating information exchange. This session presents the Empirical Characteristic Function Equality Convergence Test (EFECT), a data-driven method to quantify the reproducibility of stochastic simulation results. EFECT provides a quantitative measure of the reproducibility of stochastic results, called the EFECT Error, for modelers to determine a sample size that allows independent reproducibility studies. EFECT also provides a statistical test for performing reproducibility studies with an a priori significance, enabling modeling communities to develop standards and best practices. To this end, EFECT defines the minimum necessary information, called an EFECT Report, to facilitate exchange between modelers for reproducibility studies. The session surveys numerous applications that demonstrate EFECT enabling reproducible stochastic simulation with a variety of modeling methodologies, including ordinary differential equations with stochastic parameter sampling, stochastic differential equations, agent-based models, and uncertainty quantification in physics-informed neural networks. The session concludes with a detailed look at how a Python library implementation of EFECT, called libSSR, is enabling quantitative reproducibility in multicellular modeling as a federated, community-level activity.

Eran Agmon

University of Connecticut, USA

"Multicellular Schema with Vivarium"

As models of multicellular biology grow in complexity, there is a critical need for modular, extensible frameworks that can manage diverse biological processes across scales. This talk introduces a compositional schema approach, a methodology for constructing simulations of multicellular systems through modular, interoperable components. Central to this approach is Vivarium, an open-source software platform designed to integrate heterogeneous modeling formalisms—including ODEs, stochastic kinetics, constraint-based models, agent-based systems, and rule-based logic—into unified, hybrid simulations. I will highlight how Vivarium supports schema-driven composition of cells, their interactions, and their environments, enabling scalable simulations of tissues, microbial communities, and synthetic consortia. A flagship example is the integration of diverse mechanistic submodels in a whole-cell simulation of Escherichia coli, demonstrating Vivarium’s ability to orchestrate biological complexity through standardized schemas and modular interfaces. I will discuss design principles behind Vivarium, share emerging tools for building multicellular models, and outline future directions for collaborative, open-ended systems biology.

James Osborne

University of Melbourne, AUSTRALIA

"Multicellular Model Reproducibility: A case study, results from the Open VT hackathon"

Multicellular development is a key area of ongoing research, focussing on how tissues and organs develop and function, particularly how underlying processes fail. The last decade has seen remarkable progress in experimental studies of tissue and organ development, leading to the development of more advanced mathematical models and increased computational power. This has enabled the increased adoption of multicellular approaches to modelling the self-organisation of cells within tissues. Multicellular simulations have become indispensable in understanding complex biological phenomena, from tissue development to disease progression. However, the diversity in simulation methods, such as agent-based models, lattice-free models, and stochastic particle simulations, poses challenges in terms of reproducibility, modularity, reusability, and integration within multi-scale multicellular simulations. To address these challenges, we organised a workshop titled “Community Development of Multicellular Virtual Tissues: The OpenVT project” on the 13th of July 2025, as part of the 2025 SMB meeting. We held a Reproducibility Hackathon during the workshop to test model reproducibility and specification. In this talk, we provide an overview of the workshop and present our findings on reproducibility in multicellular simulation.

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Annual Meeting for the Society for Mathematical Biology, 2025.