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Rapid community-driven development of a SARS-CoV-2 tissue simulator

View ORCID ProfileMichael Getz, View ORCID ProfileYafei Wang, View ORCID ProfileGary An, View ORCID ProfileAndrew Becker, View ORCID ProfileChase Cockrell, View ORCID ProfileNicholson Collier, View ORCID ProfileMorgan Craig, View ORCID ProfileCourtney L. Davis, View ORCID ProfileJames Faeder, View ORCID ProfileAshlee N. Ford Versypt, View ORCID ProfileJuliano F. Gianlupi, View ORCID ProfileJames A. Glazier, View ORCID ProfileSara Hamis, View ORCID ProfileRandy Heiland, View ORCID ProfileThomas Hillen, Dennis Hou, View ORCID ProfileMohammad Aminul Islam, View ORCID ProfileAdrianne Jenner, View ORCID ProfileFurkan Kurtoglu, View ORCID ProfileBing Liu, View ORCID ProfileFiona Macfarlane, View ORCID ProfilePablo Maygrundter, View ORCID ProfilePenelope A Morel, View ORCID ProfileAarthi Narayanan, View ORCID ProfileJonathan Ozik, View ORCID ProfileElsje Pienaar, View ORCID ProfilePadmini Rangamani, View ORCID ProfileJason Edward Shoemaker, View ORCID ProfileAmber M. Smith, View ORCID ProfilePaul Macklin
doi: https://doi.org/10.1101/2020.04.02.019075
Michael Getz
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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Yafei Wang
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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Gary An
2The University of Vermont Medical Center, Burlington, VT USA
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Andrew Becker
2The University of Vermont Medical Center, Burlington, VT USA
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Chase Cockrell
2The University of Vermont Medical Center, Burlington, VT USA
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Nicholson Collier
3Decision and Infrastructure Sciences, Argonne National Laboratory. Lemont, IL USA
4Consortium for Advanced Science and Engineering, University of Chicago. Chicago, IL USA
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Morgan Craig
5Department of Mathematics, University of Montreal. Montreal, QC Canada
6CHU Sainte-Justine Research Centre, Montreal, QC Canada
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Courtney L. Davis
7Natural Science Division, Pepperdine University, Malibu, CA USA
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James Faeder
8Department of Computational and Systems Biology, University of Pittsburgh. Pittsburgh, PA USA
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Ashlee N. Ford Versypt
9School of Chemical Engineering, Oklahoma State University, Stillwater, OK USA
10Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK USA
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Juliano F. Gianlupi
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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James A. Glazier
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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Sara Hamis
11School of Mathematics and Statistics, University of St Andrews, St Andrews, Scotland
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Randy Heiland
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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Thomas Hillen
12Department of Mathematical and Statistical Sciences, University of Alberta. Edmonton, AB Canada
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Dennis Hou
13Department of Mathematics, Rutgers University. New Brunswick, NJ USA
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Mohammad Aminul Islam
9School of Chemical Engineering, Oklahoma State University, Stillwater, OK USA
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Adrianne Jenner
5Department of Mathematics, University of Montreal. Montreal, QC Canada
6CHU Sainte-Justine Research Centre, Montreal, QC Canada
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Furkan Kurtoglu
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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Bing Liu
8Department of Computational and Systems Biology, University of Pittsburgh. Pittsburgh, PA USA
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Fiona Macfarlane
11School of Mathematics and Statistics, University of St Andrews, St Andrews, Scotland
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Pablo Maygrundter
14Citizen scientist. Austin, TX USA
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Penelope A Morel
15Department of Immunology, University of Pittsburgh. Pittsburgh, PA USA
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Aarthi Narayanan
16National Center for Biodefense and Infectious Disease, George Mason University. Manassas, VA USA
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Jonathan Ozik
3Decision and Infrastructure Sciences, Argonne National Laboratory. Lemont, IL USA
4Consortium for Advanced Science and Engineering, University of Chicago. Chicago, IL USA
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Elsje Pienaar
17Weldon School of Biomedical Engineering, Purdue University. West Lafayette, IN USA
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Padmini Rangamani
18Department of Mechanical and Aerospace Engineering, University of California. San Diego, CA USA
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Jason Edward Shoemaker
19Department of Chemical and Petroleum Engineering, University of Pittsburgh. Pittsburgh, PA USA
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Amber M. Smith
20Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN USA
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Paul Macklin
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
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  • For correspondence: macklinp@iu.edu
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Abstract

The 2019 novel coronavirus, SARS-CoV-2, is an emerging 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 like diabetes. 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 rapid refinements with a two-to-four week release cycle. 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† in memoriam

  • Note: This is a rapid prototyping project. For the very latest, see http://COVID-19.physicell.org

  • This work continues a community-driven rapid prototyping of a SARS-CoV-2 tissue simulator, now updated to the version 3 model. Changes include: 1) refined biological background materials and references 2) new team members 3) v3 model prototype and results, with a focus on early immune responses 4) updated nanoHUB webapp, zenodo links, etc.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 29, 2020.
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Rapid community-driven development of a SARS-CoV-2 tissue simulator
Michael Getz, Yafei Wang, Gary An, Andrew Becker, Chase Cockrell, Nicholson Collier, Morgan Craig, Courtney L. Davis, James Faeder, Ashlee N. Ford Versypt, Juliano F. Gianlupi, James A. Glazier, Sara Hamis, Randy Heiland, Thomas Hillen, Dennis Hou, Mohammad Aminul Islam, Adrianne Jenner, Furkan Kurtoglu, Bing Liu, Fiona Macfarlane, Pablo Maygrundter, Penelope A Morel, Aarthi Narayanan, Jonathan Ozik, Elsje Pienaar, Padmini Rangamani, Jason Edward Shoemaker, Amber M. Smith, Paul Macklin
bioRxiv 2020.04.02.019075; doi: https://doi.org/10.1101/2020.04.02.019075
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Rapid community-driven development of a SARS-CoV-2 tissue simulator
Michael Getz, Yafei Wang, Gary An, Andrew Becker, Chase Cockrell, Nicholson Collier, Morgan Craig, Courtney L. Davis, James Faeder, Ashlee N. Ford Versypt, Juliano F. Gianlupi, James A. Glazier, Sara Hamis, Randy Heiland, Thomas Hillen, Dennis Hou, Mohammad Aminul Islam, Adrianne Jenner, Furkan Kurtoglu, Bing Liu, Fiona Macfarlane, Pablo Maygrundter, Penelope A Morel, Aarthi Narayanan, Jonathan Ozik, Elsje Pienaar, Padmini Rangamani, Jason Edward Shoemaker, Amber M. Smith, Paul Macklin
bioRxiv 2020.04.02.019075; doi: https://doi.org/10.1101/2020.04.02.019075

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