Iterative community-driven development of a SARS-CoV-2 tissue simulator
Iterative community-driven development of a SARS-CoV-2 tissue simulator
Abstract The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.
Macklin Paul、Mapder Tarunendu、Hamis Sara、Heiland Randy、Ozik Jonathan、Hou Dennis、Asthana Maansi、Becker Andrew、Collier Nicholson、Craig Morgan、Rangamani Padmini、Smith Amber M.、Maygrundter Pablo、Cockrell Chase、Jenner Adrianne L.、Shoemaker Jason Edward、Kurtoglu Furkan、Larkin Caroline I.、Narayanan Aarthi、Pienaar Elsje、Gianlupi Juliano F.、Macfarlane Fiona、Islam Mohammad Aminul、Ford Versypt Ashlee N.、Saglam Ali Sinan、An Gary、Weaver Jordan J.A.、Liu Bing、Faeder James R.、Glazier James A.、Getz Michael、Hillen Thomas、Wang Yafei、Morel Penelope A、Davis Courtney L.
Department of Intelligent Systems Engineering, Indiana UniversityDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of MedicineSchool of Mathematics and Statistics, University of St AndrewsDepartment of Intelligent Systems Engineering, Indiana UniversityDecision and Infrastructure Sciences, Argonne National Laboratory||Consortium for Advanced Science and Engineering, University of ChicagoDepartment of Mathematics, Rutgers UniversityAgricultural and Biological Engineering, Purdue UniversityThe University of Vermont Medical CenterDecision and Infrastructure Sciences, Argonne National Laboratory||Consortium for Advanced Science and Engineering, University of ChicagoDepartment of Mathematics, University of Montreal||Sainte-Justine University Hospital Research CentreDepartment of Mechanical and Aerospace Engineering, University of CaliforniaDepartment of Pediatrics, University of Tennessee Health Science CenterCitizen scientistThe University of Vermont Medical CenterDepartment of Mathematics, University of Montreal||Sainte-Justine University Hospital Research CentreDepartment of Chemical and Petroleum Engineering, University of PittsburghDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Computational and Systems Biology, University of PittsburghNational Center for Biodefense and Infectious Disease, George Mason UniversityWeldon School of Biomedical Engineering, Purdue UniversityDepartment of Intelligent Systems Engineering, Indiana UniversitySchool of Mathematics and Statistics, University of St AndrewsSchool of Chemical Engineering, Oklahoma State University||Department of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkSchool of Chemical Engineering, Oklahoma State University||Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University||Department of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Computational and Systems Biology, University of PittsburghThe University of Vermont Medical CenterDepartment of Chemical and Petroleum Engineering, University of PittsburghDepartment of Computational and Systems Biology, University of PittsburghDepartment of Computational and Systems Biology, University of PittsburghDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Mathematical and Statistical Sciences, University of AlbertaDepartment of Intelligent Systems Engineering, Indiana UniversityDepartment of Immunology, University of PittsburghNatural Science Division, Pepperdine University
基础医学生物科学研究方法、生物科学研究技术分子生物学
Macklin Paul,Mapder Tarunendu,Hamis Sara,Heiland Randy,Ozik Jonathan,Hou Dennis,Asthana Maansi,Becker Andrew,Collier Nicholson,Craig Morgan,Rangamani Padmini,Smith Amber M.,Maygrundter Pablo,Cockrell Chase,Jenner Adrianne L.,Shoemaker Jason Edward,Kurtoglu Furkan,Larkin Caroline I.,Narayanan Aarthi,Pienaar Elsje,Gianlupi Juliano F.,Macfarlane Fiona,Islam Mohammad Aminul,Ford Versypt Ashlee N.,Saglam Ali Sinan,An Gary,Weaver Jordan J.A.,Liu Bing,Faeder James R.,Glazier James A.,Getz Michael,Hillen Thomas,Wang Yafei,Morel Penelope A,Davis Courtney L..Iterative community-driven development of a SARS-CoV-2 tissue simulator[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2020.04.02.019075.点此复制
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