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IMAG/MSM Working Group on Multiscale Modeling and Viral Pandemics Mini Seminars

Oct 7, 2021

Welcome - The meeting will start at 3PM EDT

NOTE: THE MEETING WILL BE RECORDED, STREAMED AND PUBLICLY AVAILABLE�FOR THOSE MEMBERS UNABLE TO ATTEND

Agenda

Welcome
Links, people, other info
Social media links
Quick Announcements
Upcoming Mini-Seminars and Request for Future Speakers
David O’Connor, University of Wisconsin, Title: Implications of Israel's aggressive third dose vaccine program.
Shelby O’Connor, University of Wisconsin, Title: Air surveillance for respiratory pathogens in Dane County communities.
Request for Further Business

Note we are using more stringent security for our Zoom meetings. �You will now need to use the link in the email that you get after signing up.

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People

Co-Lead: Reinhard Laubenbacher, PhD

Department of Medicine

Laboratory for Systems Medicine

University of Florida

reinhard.laubenbacher@medicine.ufl.edu

Co-Lead: James A. Glazier, PhD

Dept. of Intelligent Systems Engineering and Biocomplexity Institute

Indiana University, Bloomington

jaglazier@gmail.com

Web Administration, Slack: James P. Sluka, PhD

Dept. of Intelligent Systems Engineering and Biocomplexity Institute

Indiana University, Bloomington

jsluka@indiana.edu

Activities Coordination: Bruce G. Shapiro, PhD, PMP

Laboratory for Systems Medicine

University of Florida

bruce.shapiro@medicine.ufl.edu

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Slack Channel

https://Msm-working-group.slack.com

Twitter

https://twitter.com/MsmViral

Our IMAG/MSM Wiki page

https://www.imagwiki.nibib.nih.gov/working-groups/multiscale-modeling-and-viral-pandemics Feel free to suggest additional content!

Or, use the Tiny URL: https://tinyurl.com/hkr97vfe

IMAG’s LinkedIn

https://www.linkedin.com/groups/12095434?lipi=urn%3Ali%3Apage%3Ad_flagship3_search_srp_all%3B1FVndkN2SD6P0xj2PYfqdQ%3D%3D

YouTube “MSM Working Group on Multiscale Modeling” https://www.youtube.com/channel/UCuDFvhgFziRRDcpRnT3vlrw

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Announcements

�Any short (~1 minute) items such as;

announcements
meetings
funding
publications
requests for help
???

If you have not done so yet, please fill out the short survey at https://forms.gle/F3j4tS45skDpW4pD8

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Schedule for Upcoming Meetings and mini-Seminars

Oct 14:

Balazs Madas, Centre for Energy Research, Budapest, Budapest, Hungary, Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated droplets and aerosol particles.
Yinon Moise Bar-On, PhD Student Weizmann Institute of Science.

Oct 21:

Jason Shoemaker, University of Pittsburgh.
Tiam Heydari, University of British Columbia, �IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data https://doi.org/10.1101/2021.04.01.438014

Oct 28:

Russ Taylor, JHU Robotics for the ICU
David Forgacs, University of Georgia. SARS-CoV-2 research

Request for future speakers (Dec 2, Dec 9, …)

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Rules of the Meeting

Please mute your microphone and hold questions until after the presentations

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Mini-Seminar� Implications of Israel's aggressive third dose �vaccine program

David O’Connor�Professor of pathology and laboratory medicine, �University of Wisconsin

Israel began an aggressive COVID-19 immunization program before most other countries. Consequently, they were among the first to observe waning immunity. This prompted Israel to begin an ambitious real-world experiment to provide third doses of the Pfizer/BioNTech vaccine to those who were initially vaccinated at least five months previously. The early results show dramatic protection from both severe illness and mild cases among older individuals who were the first to receive the vaccine. In this presentation I will summarize the Israeli data and discuss why I think other countries including the US should implement similar programs as soon as possible.

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Mini-Seminar�Air surveillance for respiratory pathogens in �Dane County communities

Shelby O’Connor�Professor of pathology and laboratory medicine, �University of Wisconsin

The COVID-19 pandemic has highlighted how underprepared our community is to detect circulating respiratory viruses. Predictive warning systems for these viruses are needed. For the past several months, we have been piloting Thermo AerosolSense air samplers in University, hospital, and other community settings. We have detected SARS-CoV-2 genetic material in air samples collected at many of these sites. In the future, we propose adapting this system for widespread use in K-12 schools to support ongoing mitigation strategies and provide additional virus detection methods for school communities.

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Requests for Input/Suggestions

We would like the subgroup leads to prepare brief presentations for the Thursday meetings, please let us know when you would like to present

Ideas/help for publicising our Thursday mini-seminars more effectively and for speakers to invite

Suggestions for agenda items and approaches to organizing the Steering Committee Meetings more effectively

There have also been a number of requests for more explicit statements of goals and tasks from the WG leadership, we would appreciate your suggestions

Please contact Reinhard Laubenbacher, James Glazier, James Sluka or Bruce Shapiro with your ideas on all of these issues

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fini

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Mini-Seminar�Optimizing predictive models to prioritize viral discovery�in zoonotic reservoirs

Daniel Becker�University of Oklahoma

Identifying and monitoring the wildlife reservoirs of novel zoonotic viruses remains logistically challenging and costly. Statistical models can be used to guide sampling prioritization, but predictions from any given model may be highly uncertain; moreover, systematic model validation is rare, and the drivers of model performance are consequently under-documented. Here, we use bat hosts of betacoronaviruses as a case study for the data-driven process of comparing and validating predictive models of likely reservoir hosts. In the first quarter of 2020, we generated an ensemble of eight statistical models that predict host-virus associations and developed priority sampling recommendations for potential bat reservoirs. Over a year, we tracked the discovery of 40 new bat hosts of betacoronaviruses, validated initial predictions, and dynamically updated our analytic pipeline. We find that ecological trait-based models perform extremely well at predicting these novel hosts, whereas network methods consistently perform roughly as well or worse than expected at random. These findings illustrate the importance of ensembling as a buffer against variation in model quality and highlight the value of including host ecology in predictive models. Our revised models show improved performance and predict over 400 bat species globally that could be undetected hosts of betacoronaviruses. Although 20 species of rhinolophid bats are known to be the primary reservoir of SARS-like viruses, we find at least three-fourths of plausible betacoronavirus reservoirs in this bat genus might still be undetected. Our study is the first to show via systematic validation that machine learning models can help optimize wildlife sampling for undiscovered viruses and illustrates how such approaches are best implemented through a dynamic process of prediction, data collection, validation, and updating. Lastly, we discuss next steps to systematically integrate within-host data streams into future modeling efforts.

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Mini-Seminar�Quantitative Modeling and Simulation to Drive Critical Decisions from Research through Clinical Trials

John Burke

CEO, President, and Co-founder, Applied BioMath

Quantitative Systems Pharmacology (QSP) is a mathematical modeling and engineering approach that aims to quantitatively integrate knowledge about therapeutics with an understanding of its mechanism of action in the context of human disease mechanisms.

Several examples will be shown which highlight QSP efforts to accelerate the discovery and development of best-in-class therapeutics and impact critical decisions, in the continuum from preclinical exploration to clinical research

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Have you made new research contacts or collaborations based on the Viral Pandemics working group?

New collaborations that come out of this working group is an important metric of our success.

If you have new collaborations could you let the WG leads know?

co-writing a paper?
preparing a grant proposal?
preparing a teaching or modeling resource?
simply extensive discussions?

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Additional Business

We ask that everyone sign up for subgroups using the Google Form at

https://forms.gle/Vf6RtapTeXfXLBaq6

People are welcome to post tools and software to IMAG/MSM website, but be careful to be clear that a posting does not include endorsement by NIH

Please register on IMAG/MSM web site https://www.imagwiki.nibib.nih.gov/index.php/�(Details are on the next slide)

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Charge to subgroups�(review):

Deliverable: White paper on the subgroup focus areas.�Due date: February 26, 2021

Steps to be taken:

Subgroup lead(s) write one or two paragraphs on the topic of the subgroup and the main problems to be focused on. Due to working group leads: January 17
Email to all subgroup members with this description and call for an initial meeting (if not happened yet) on or before January 26. Bruce can help with address lists and scheduling.
At the initial meeting, discussion of the main topics of a white paper that surveys the subgroup topic and lists major problems and potential solutions.
Subsequently, subgroup leads develop a document based on the meeting with sections for main topics and find leads for each of the sections. Completed by January 29.
Leads for main topics draw on other subgroup members to complete an initial draft by �February 12.
Entire subgroup edits, refines, expands document, including references etc. Final document delivered to working group leads by February 26.

Should be added to the subgroup’s Wiki page

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IMAG/MSM Wiki Pages

The Viral Pandemics WG has an IMAG/MSM Wiki page at:�https://www.imagwiki.nibib.nih.gov/working-groups/multiscale-modeling-and-viral-pandemics

In addition, each subgroup can have their own WIki page.

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IMAG/MSM Wiki Pages

We ask that:

Each group identify someone to update their group’s Wiki page.

If the group prefers, they can maintain a page outside the IMAG Wiki (for example, at SimTK or GitHub)

To update your group’s Wiki;

Contact Jim Sluka (JSluka@iu.edu) and I will copy the subgroup template to a new page for your subgroup.
Register as a member of the IMAG/MSMS so you have edit-access to all the Wiki page. (Details are on the next page or contact jsluka@iu.edu.)

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To register for the MSM�(Multiscale Modeling Consortium):

https://www.imagwiki.nibib.nih.gov/index.php/
In the upper right select “LOG IN”
Select “Create new account”
Select the “To edit the wiki as a MSM member”
Fill out the name, email etc. fields
In the “WG Involvement*” box scroll down and select

“Multiscale Modeling and Viral Pandemics”

In the “MSM funded project title” enter the title for any grants or other funding sources you would like to acknowledge.
“MSM Resources” you can leave blank
“MSM grant no.” enter the grant number for the project entered in #7. If there is no number enter 000000
Enter project start and end dates, these can be approximate.
The remaining fields are all optional.

If you have any problems please contact JSluka@iu.edu

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Current Subgroup Updates

The Drug Development subgroup was left off the initial subgroup joining form (Robert Stratford and Jim Sluka).

If anyone is interested in joining this subgroup please email Bruce bruce.shapiro@medicine.ufl.edu

We may merge the slack channels for “drug development” and “therapeutics-and-medicine”

Merged sub groups:

[Integration Within and Across Scales and challenges]
[Integration Between Within-host and Population Scales]
Now “Integration” LEADS: J Barhak, R Bowness, Y Liu, R Thompson

Merged sub groups:

[Dissemination, training and outreach to the public, research community and Liaisons]
[Health Equity]
Leads: T Helikar, B Madamanchi, J Rice

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Subgroup Roll Call and Feedback

Subgroup leads quick check in (subgroup list on next slides):

Has your group met yet?
Do you have a future meeting schedule set (date of next meeting, if scheduled)?
Anything to report?

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Subgroups 1 of 2�(28 total subgroups)

Leads Names

Physiological Models

[Innate and Adaptive Immune Response] J Shoemaker, R Datta, V Zarnitsyna, E Schwartz

[Host-pathogen Interactions] Y Liu, J Thakar, W Garira

[Tissue Damage and Recovery] Y Jiang, K Ye

Virus Models

[Viral Transport and Modes of Entry and Barrier Functions] MG Forest

[Viral Replication and Release] J Faeder, P Rangamani, EY Kim

[Viral Evolution] F Adler, A Zilman

Therapeutics and Medicine

[Drug Development] R Stratford

[Vaccine Development] K Ye, E Schwartz

[Modeling individual responses to disease and treatment] G An, E Schwartz, T Mapder

[Modelling Decontamination of Surfaces/Materials] K Kiradjiev

[Machine Learning for Health Monitoring] G Lin, Y Jiang

Individual Organ Systems

[Lungs] Y Jiang

[Heart],[Vasculature] C Lynch

[Kidney and Liver] M Rafailovich, C Mazza, C Mahapatra, C Yedjou

[Comorbidities] J Barhak, G Gonzalez-Parra

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Subgroups 2 of 2

Data

[Experimental and Clinical Data for Model Construction and Validation] S Schnell

[AI-based Data Processing, Heterogeneous Data Fusion] O Gevaert, Y Kevrekidis

[Infection in experimental models including Relationship between in vivo � and in vitro responses and Infection in vivo model organisms] tbd

[Infection in zoonotic reservoir animals and Interspecies Transmission] G An, J Rice, T Mapder

[Coinfection and/or other pathogens] H. Dobrovolny

[Emerging and Reemerging Diseases] A Gumel

Modeling Technology

[Aerosol Transport in Lung, Lymph and Blood] M Tawhai, C Darquenne

[Integration] ** J Barhak, R Bowness, Y Liu, R Thompson

[Knowledge Acquisition and Modeling] SMR Naqvi, J Thakar

[Crowd-sourcing Models] R Laubenbacher, P Macklin

[Model Standards, Credibility, and Annotation] J Barhak, R Sheriff

�Social Issues

[Dissemination, training and outreach to the public, � research community and Liaisons] T Helikar, B Madamanchi, J Rice

[Health Equity] *** B Madamanchi

[Dissemination and Communication to funding agencies] J Glazier, R Laubenbacher

** Merged two groups – � [Integration Within and Across Scales and challenges]

[Integration Between Within-host and Population Scales]

*** Merged

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Please Sign Up For Subgroups!

Subgroup Sign up

We ask that everyone sign up for subgroups using the Google Form at:

https://forms.gle/Vf6RtapTeXfXLBaq6

�The form allows you to join a group and volunteer to lead. If you think subgroups overlap, feel free to sign up for multiple groups. We will likely combine some of the groups based on the number of participants and the number of people common across related groups.

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Discussion of Recruitment of Subgroup Leads, Subgroup Members and WG Members

Procedure for the establishment of new subgroups:

New subgroup proposals should include a brief description of the focus, at least one person who has agreed to lead the subgroup, and a rationale why the proposed subgroup focus is not covered by already existing subgroups.

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Review of Web Site and Contents

Please review the web site and make suggestions for improvements in contents:

https://www.imagwiki.nibib.nih.gov/working-groups/multiscale-modeling-and-viral-pandemics

We can add linked pages for each subgroup.