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Learn.: Sci. Technol."],"published-print":{"date-parts":[[2025,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mechanistic, multicellular, agent-based models are commonly used to investigate tissue, organ, and organism-scale biology at single-cell resolution. The Cellular-Potts Model (CPM) is a powerful and popular framework for developing and interrogating these models. CPMs become computationally expensive at large space- and time- scales making application and investigation of developed models difficult. Surrogate models may allow for the accelerated evaluation of CPMs of complex biological systems. However, the stochastic nature of these models means each set of parameters may give rise to different model configurations, complicating surrogate model development. In this work, we leverage denoising diffusion probabilistic models (DDPMs) to train a generative AI surrogate of a CPM used to investigate\n                    <jats:italic>in vitro<\/jats:italic>\n                    vasculogenesis. We describe the use of an image classifier to learn the characteristics that define unique areas of a 2-dimensional parameter space. We then apply this classifier to aid in surrogate model selection and verification. Our CPM model surrogate generates model configurations 20,000 timesteps ahead of a reference configuration and demonstrates approximately a 22x reduction in computational time as compared to native code execution. Our work represents a step towards the implementation of DDPMs to develop digital twins of stochastic biological systems.\n                  <\/jats:p>","DOI":"10.1088\/2632-2153\/ae11f8","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:51:53Z","timestamp":1760136713000},"page":"045024","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Generative diffusion model surrogates for mechanistic agent-based biological models"],"prefix":"10.1088","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-2703","authenticated-orcid":true,"given":"Tien","family":"Comlekoglu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6212-1033","authenticated-orcid":true,"given":"J","family":"Quetzalcoatl Toledo-Mar\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-1588","authenticated-orcid":false,"given":"Douglas W","family":"DeSimone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5857-5606","authenticated-orcid":false,"given":"Shayn M","family":"Peirce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-1391","authenticated-orcid":false,"given":"Geoffrey","family":"Fox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3634-190X","authenticated-orcid":false,"given":"James A","family":"Glazier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"mlstae11f8bib1","first-page":"pp 325","type":"book","article-title":"Chapter 13 - multi-scale modeling of tissues using Compucell3D","volume":"vol 110","author":"Swat","year":"2012"},{"key":"mlstae11f8bib2","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1093\/bioinformatics\/btt772","type":"journal-article","article-title":"Morpheus: a user-friendly modeling environment for multiscale and multicellular systems biology","volume":"30","author":"Starru\u00df","year":"2014","journal-title":"Bioinformatics"},{"key":"mlstae11f8bib3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.61288","type":"journal-article","article-title":"Artistoo, a library to build, share and explore simulations of cells and tissues in the web browser","volume":"10","author":"Wortel","year":"2021","journal-title":"eLife"},{"key":"mlstae11f8bib4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.ydbio.2005.10.003","type":"journal-article","article-title":"Cell elongation is key to in silico replication of in vitro vasculogenesis and subsequent remodeling","volume":"289","author":"Merks","year":"2006","journal-title":"Dev. 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