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However, translating these rich data sets into mechanistic insight remains a significant challenge. Agent-based models (ABMs) are a bottom-up computational framework for investigating the emergent behavior of cell populations that can arise from rules defining the interactions between individual neighboring cells, while topological data analysis (TDA) provides robust descriptors of spatial organization. We present TOPAZ (TOpologically-based Parameter inference for Agent-based model optimiZation), a computational pipeline that integrates TDA with approximate Bayesian computation (ABC), approximate approximate Bayesian computation (AABC), and Bayesian model selection to identify biologically plausible ABMs from spatiotemporal cellular data. TOPAZ uses persistent homology to quantify spatial features of cell trajectories and combines this topological information with parameter inference via ABC and AABC and model comparison using the Bayesian information criterion. We validate TOPAZ using simulations of collective fibroblast movement, demonstrating its ability to accurately recover model parameters and distinguish between a baseline ABM and an extended model that incorporates an alignment interaction. Our results and open-source code demonstrate the utility of TOPAZ as an extensible framework for mechanistic inference and model discrimination in spatial single-cell analysis.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014801","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:54:28Z","timestamp":1790358868000},"page":"e1014801","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Topologically-based parameter inference for agent-based model selection from spatiotemporal cellular data"],"prefix":"10.1371","volume":"22","author":[{"given":"Alyssa R.","family":"Wenzel","sequence":"first","affiliation":[{"name":"North Carolina State University","place":["Raleigh, North Carolina, United States of America"],"department":["Department of Mathematics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick 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