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Integrative multiscale modeling confronts the complexity of biology by combining heterogeneous datasets and diverse modeling strategies into unified representations. These integrated models are then run to simulate how the hypothesized mechanisms operate as a whole. But building such models has been a labor-intensive process that requires many contributors, and they are still primarily developed on a case-by-case basis with each project starting anew. New software tools that streamline the integrative modeling effort and facilitate collaboration are therefore essential for future computational biologists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Vivarium is a software tool for building integrative multiscale models. It provides an interface that makes individual models into modules that can be wired together in large composite models, parallelized across multiple CPUs and run with Vivarium\u2019s discrete-event simulation engine. Vivarium\u2019s utility is demonstrated by building composite models that combine several modeling frameworks: agent-based models, ordinary differential equations, stochastic reaction systems, constraint-based models, solid-body physics and spatial diffusion. This demonstrates just the beginning of what is possible\u2014Vivarium will be able to support future efforts that integrate many more types of models and at many more biological scales.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The specific models, simulation pipelines and notebooks developed for this article are all available at the vivarium-notebooks repository: https:\/\/github.com\/vivarium-collective\/vivarium-notebooks. Vivarium-core is available at https:\/\/github.com\/vivarium-collective\/vivarium-core, and has been released on Python Package Index. The Vivarium Collective (https:\/\/vivarium-collective.github.io) is a repository of freely available Vivarium processes and composites, including the processes used in Section 3. Supplementary Materials provide with an extensive methodology section, with several code listings that demonstrate the basic interfaces.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac049","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T15:19:40Z","timestamp":1643383180000},"page":"1972-1979","source":"Crossref","is-referenced-by-count":32,"title":["Vivarium: an interface and engine for integrative multiscale modeling in computational biology"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1279-2474","authenticated-orcid":false,"given":"Eran","family":"Agmon","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Stanford University , Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-3142","authenticated-orcid":false,"given":"Ryan K","family":"Spangler","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University , Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-7331","authenticated-orcid":false,"given":"Christopher J","family":"Skalnik","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University , Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2958-6776","authenticated-orcid":false,"given":"William","family":"Poole","sequence":"additional","affiliation":[{"name":"Computation and Neural Systems, California Institute of Technology , Pasadena, CA 91125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5857-5606","authenticated-orcid":false,"given":"Shayn M","family":"Peirce","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia , Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9414-6999","authenticated-orcid":false,"given":"Jerry H","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University , Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-8912","authenticated-orcid":false,"given":"Markus W","family":"Covert","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University , Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"2023020404003641900_btac049-B1","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3390\/e22101101","article-title":"A multi-scale approach to modeling E. coli chemotaxis","volume":"22","author":"Agmon","year":"2020","journal-title":"Entropy"},{"key":"2023020404003641900_btac049-B2","doi-asserted-by":"crossref","first-page":"e1000705","DOI":"10.1371\/journal.pcbi.1000705","article-title":"Detailed simulations of cell biology with Smoldyn 2.1","volume":"6","author":"Andrews","year":"2010","journal-title":"PLoS Comput. 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