{
  "abstract": "Building multiscale biological models requires the integration of independently developed submodels, which means moving shared variables between them and coordinating when each submodel runs. Existing tools typically address isolated biological mechanisms with specific numerical methods, rarely specify which variables each model reads and writes, how those variables are translated, and how model updates are synchronized. We present Process Bigraph, a framework for composing and simulating multiscale models. Process Bigraph generalizes the architectural ideas previously used in the Vivarium software into a shared specification that describes process interfaces, hierarchical data structures, composition patterns, and orchestration patterns. The paper explains how the framework is organized and why it makes biological models easier to understand, reuse, and build on; S1 Text provides the formal specification. We introduce Vivarium 2.0 as an open-source implementation of the process bigraph framework. We demonstrate its utility with Spatio-Flux, a standalone library of microbial ecosystem simulations that combine kinetic equations, dynamic flux balance analysis, and different spatial processes. These simulations illustrated how the framework effectively integrates diverse biological processes, leading to emergent spatially organized population dynamics. Finally, we discuss implications for emerging multiscale modeling standards. Availability and implementation: Vivarium 2.0 is a suite of software libraries that include: (1) bigraph-schema, for defining and operating on data types within a hierarchical JSON-based format; (2) process-bigraph, for defining process interfaces, composite simulations, and executing them; and (3) viva-superpowers, for AI-assisted construction and composition of process bigraphs. Spatio-Flux is a reference application used in this paper to demonstrate the framework’s utility. S1 Text provides detailed descriptions of these software libraries. All software is open-source and available at: https://github.com/vivarium-collective. Author summary: Biology spans many scales, from molecules and cells to tissues and whole organisms, and no single computer model can capture all of them at once. Researchers instead build many specialized models, each describing one piece of biology with its own methods and assumptions. Combining these separate models into a single working simulation is difficult: it is often unclear which quantities each model shares, how those quantities should be translated between models, and in what order the models should run. We introduce Process Bigraph, a framework that treats each model as a self-contained “process” with a clearly labeled interface describing exactly what it reads and writes. Processes connect to one another through shared, typed data, and a common engine coordinates when each one runs. This makes multiscale models easier to understand, reuse, and build on together. We provide an open-source implementation, Vivarium 2.0, and demonstrate it with Spatio-Flux, a suite of microbial-community simulations that combine metabolism, movement, and space. Together, these tools offer shared infrastructure for assembling the diverse models of systems biology into unified, reproducible simulations.",
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  "affiliations": [
    "Center for Cell Analysis and Modeling, University of Connecticut Health, Farmington, Connecticut, United States of America."
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  "author_total": 2,
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      "name": "Eran Agmon",
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      "name": "Ryan K Spangler"
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  "doi": "10.1371/journal.pcbi.1014819",
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  "pmcid": "PMC13652326",
  "pmid": "42853869",
  "published": "2026-10-09",
  "publisher": "Public Library of Science",
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  "title": "Process bigraphs and the architecture of compositional systems biology",
  "title_text": "Process bigraphs and the architecture of compositional systems biology",
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