Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

View ORCID ProfileMichael Getz, View ORCID ProfileYafei Wang, View ORCID ProfileGary An, Maansi Asthana, View ORCID ProfileAndrew Becker, View ORCID ProfileChase Cockrell, View ORCID ProfileNicholson Collier, View ORCID ProfileMorgan Craig, View ORCID ProfileCourtney L. Davis, View ORCID ProfileJames R. Faeder, View ORCID ProfileAshlee N. Ford Versypt, View ORCID ProfileTarunendu Mapder, 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 L. Jenner, View ORCID ProfileFurkan Kurtoglu, View ORCID ProfileCaroline I. Larkin, 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 ProfileAli Sinan Saglam, View ORCID ProfileJason Edward Shoemaker, View ORCID ProfileAmber M. Smith, View ORCID ProfileJordan J.A. Weaver, 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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael Getz
Yafei Wang
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yafei Wang
Gary An
2The University of Vermont Medical Center, Burlington, VT USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gary An
Maansi Asthana
23Agricultural and Biological Engineering, Purdue University. West Lafayette, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Becker
2The University of Vermont Medical Center, Burlington, VT USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew Becker
Chase Cockrell
2The University of Vermont Medical Center, Burlington, VT USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Chase Cockrell
Nicholson Collier
3Decision and Infrastructure Sciences, Argonne National Laboratory. Lemont, IL USA
4Consortium for Advanced Science and Engineering, University of Chicago. Chicago, IL USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicholson Collier
Morgan Craig
5Department of Mathematics, University of Montreal. Montreal, QC Canada
6Sainte-Justine University Hospital Research Centre, Montreal, QC Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Morgan Craig
Courtney L. Davis
7Natural Science Division, Pepperdine University, Malibu, CA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Courtney L. Davis
James R. Faeder
8Department of Computational and Systems Biology, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for James R. Faeder
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
11Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ashlee N. Ford Versypt
Tarunendu Mapder
22Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tarunendu Mapder
Juliano F. Gianlupi
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Juliano F. Gianlupi
James A. Glazier
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for James A. Glazier
Sara Hamis
12School of Mathematics and Statistics, University of St Andrews, St Andrews, Scotland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sara Hamis
Randy Heiland
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Randy Heiland
Thomas Hillen
13Department of Mathematical and Statistical Sciences, University of Alberta. Edmonton, AB Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Thomas Hillen
Dennis Hou
14Department of Mathematics, Rutgers University. New Brunswick, NJ USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mohammad Aminul Islam
9School of Chemical Engineering, Oklahoma State University, Stillwater, OK USA
11Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mohammad Aminul Islam
Adrianne L. Jenner
5Department of Mathematics, University of Montreal. Montreal, QC Canada
6Sainte-Justine University Hospital Research Centre, Montreal, QC Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Adrianne L. Jenner
Furkan Kurtoglu
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Furkan Kurtoglu
Caroline I. Larkin
8Department of Computational and Systems Biology, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Caroline I. Larkin
Bing Liu
8Department of Computational and Systems Biology, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bing Liu
Fiona Macfarlane
12School of Mathematics and Statistics, University of St Andrews, St Andrews, Scotland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Fiona Macfarlane
Pablo Maygrundter
15Citizen scientist. Austin, TX USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pablo Maygrundter
Penelope A Morel
16Department of Immunology, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Penelope A Morel
Aarthi Narayanan
17National Center for Biodefense and Infectious Disease, George Mason University. Manassas, VA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Aarthi Narayanan
Jonathan Ozik
3Decision and Infrastructure Sciences, Argonne National Laboratory. Lemont, IL USA
4Consortium for Advanced Science and Engineering, University of Chicago. Chicago, IL USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jonathan Ozik
Elsje Pienaar
18Weldon School of Biomedical Engineering, Purdue University. West Lafayette, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Elsje Pienaar
Padmini Rangamani
19Department of Mechanical and Aerospace Engineering, University of California. San Diego, CA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Padmini Rangamani
Ali Sinan Saglam
8Department of Computational and Systems Biology, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ali Sinan Saglam
Jason Edward Shoemaker
20Department of Chemical and Petroleum Engineering, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jason Edward Shoemaker
Amber M. Smith
21Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Amber M. Smith
Jordan J.A. Weaver
20Department of Chemical and Petroleum Engineering, University of Pittsburgh. Pittsburgh, PA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jordan J.A. Weaver
Paul Macklin
1Department of Intelligent Systems Engineering, Indiana University. Bloomington, IN USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Paul Macklin
  • For correspondence: macklinp@iu.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† in memoriam

  • This work continues a community-driven rapid prototyping of a SARS-CoV-2 tissue simulator, now updated to the version 5 model. Changes include: 1) v5 model prototype and results, with a focus on plasma and B cell types, updated macrophage polarization, and neutralizing antibodies 2) New investigations on the overall immune response, including the first model runs to successfully eliminate the virus. 3) First investigations to show that prior infections (and immune responses) are protective against subsequent viral exposures 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.
Back to top
PreviousNext
Posted November 10, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Iterative community-driven development of a SARS-CoV-2 tissue simulator
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Iterative community-driven development of a SARS-CoV-2 tissue simulator
Michael Getz, Yafei Wang, Gary An, Maansi Asthana, Andrew Becker, Chase Cockrell, Nicholson Collier, Morgan Craig, Courtney L. Davis, James R. Faeder, Ashlee N. Ford Versypt, Tarunendu Mapder, Juliano F. Gianlupi, James A. Glazier, Sara Hamis, Randy Heiland, Thomas Hillen, Dennis Hou, Mohammad Aminul Islam, Adrianne L. Jenner, Furkan Kurtoglu, Caroline I. Larkin, Bing Liu, Fiona Macfarlane, Pablo Maygrundter, Penelope A Morel, Aarthi Narayanan, Jonathan Ozik, Elsje Pienaar, Padmini Rangamani, Ali Sinan Saglam, Jason Edward Shoemaker, Amber M. Smith, Jordan J.A. Weaver, Paul Macklin
bioRxiv 2020.04.02.019075; doi: https://doi.org/10.1101/2020.04.02.019075
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Iterative community-driven development of a SARS-CoV-2 tissue simulator
Michael Getz, Yafei Wang, Gary An, Maansi Asthana, Andrew Becker, Chase Cockrell, Nicholson Collier, Morgan Craig, Courtney L. Davis, James R. Faeder, Ashlee N. Ford Versypt, Tarunendu Mapder, Juliano F. Gianlupi, James A. Glazier, Sara Hamis, Randy Heiland, Thomas Hillen, Dennis Hou, Mohammad Aminul Islam, Adrianne L. Jenner, Furkan Kurtoglu, Caroline I. Larkin, Bing Liu, Fiona Macfarlane, Pablo Maygrundter, Penelope A Morel, Aarthi Narayanan, Jonathan Ozik, Elsje Pienaar, Padmini Rangamani, Ali Sinan Saglam, Jason Edward Shoemaker, Amber M. Smith, Jordan J.A. Weaver, Paul Macklin
bioRxiv 2020.04.02.019075; doi: https://doi.org/10.1101/2020.04.02.019075

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4383)
  • Biochemistry (9599)
  • Bioengineering (7092)
  • Bioinformatics (24863)
  • Biophysics (12615)
  • Cancer Biology (9957)
  • Cell Biology (14354)
  • Clinical Trials (138)
  • Developmental Biology (7949)
  • Ecology (12107)
  • Epidemiology (2067)
  • Evolutionary Biology (15989)
  • Genetics (10925)
  • Genomics (14743)
  • Immunology (9869)
  • Microbiology (23676)
  • Molecular Biology (9485)
  • Neuroscience (50870)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2683)
  • Physiology (4015)
  • Plant Biology (8657)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2397)
  • Systems Biology (6436)
  • Zoology (1346)