: Modular design of multiscale models, with an application to the innate immune response to fungal respiratory pathogens

Investigators
Reinhard Laubenbacher, Borna Mehrad, William Schroeder
Contact info (email)
Reinhard.laubenbacher@medicine.ufl.edu
1. Define context(s)
identify/explore new therapies
reveal new biological insights
Current Conformance Level / Target Conformance Level
Comprehensive
Primary goal of the model/tool/database

Provides a virtual laboratory for an immunologist to explore the early phases of the immune response to respiratory fungal infections and test possible new interventions.

Biological domain of the model
Immunology
Structure(s) of interest in the model
Alveolar structure/Lung tissue
Spatial scales included in the model
Intracellular; cellular; tissue; whole-body
Time scales included in the model
Minutes to days
2. Data for building and validating the model
Data for building the model Published? Private? How is credibility checked? Current Conformance Level / Target Conformance Level
in vitro (primary cells cell, lines, etc.) Yes Flow cytometry Extensive
ex vivo (excised tissues)
in vivo pre-clinical (lower-level organism or small animal) Yes Flow cytometry;staining Extensive
in vivo pre-clinical (large animal)
Human subjects/clinical
Other: ________________________
Data for validating the model Published? Private? How is credibility checked? Current Conformance Level / Target Conformance Level
in vitro (primary cells cell, lines, etc.)
ex vivo (excised tissues)
in vivo pre-clinical (lower-level organism or small animal)
in vivo pre-clinical (large animal)
Human subjects/clinical
Other: ________________________
3. Validate within context(s)
Who does it? When does it happen? How is it done? Current Conformance Level / Target Conformance Level
Verification Both modelers and experimentalists Continuously Extensive
Validation Borna Mehrad When data becomes available Mouse models;histopathology Extensive
Uncertainty quantification
Sensitivity analysis Reinhard Laubenbacher's lab Continuously Extensive
Other:__________
Additional Comments
4. Limitations
Disclaimer statement (explain key limitations) Who needs to know about this disclaimer? How is this disclaimer shared with that audience? Current Conformance Level / Target Conformance Level
No adaptive immunity Everyone Documentation Extensive
Some innate immune cell types missing Everyone Documentation Extensive
Limited to iron mediated mechanisms Everyone Documentation Extensive
Simple models for epithelium/endothelium Everyone Documentation Extensive
5. Version control
Current Conformance Level / Target Conformance Level
Extensive
Naming Conventions? Repository? Code Review?
individual modeler Diverse Github Unit testing/continuous integration
within the lab Diverse Github Unit testing/continuous integration
collaborators Diverse Github Unit testing/continuous integration
6. Documentation
Current Conformance Level / Target Conformance Level
Code commented? Adequate
Scope and intended use described? Partial
User’s guide? Partial
Developer’s guide? Partial
7. Dissemination
Current Conformance Level / Target Conformance Level
Partial
Target Audience(s): “Inner circle” Scientific community Public
Simulations nutritionallungimmunity.org;Github;Girder Publications and presentations
Models nutritionallungimmunity.org;Github;Girder Publications and presentations
Software nutritionallungimmunity.org;Github;Girder Publications and presentations
Results
Implications of results
8. Independent reviews
Current Conformance Level / Target Conformance Level
Extensive
Reviewer(s) name & affiliation: Filippo Castiglione
When was review performed? Fall 2020
How was review performed and outcomes of the review? In person site visit with whole project team. Overall satisfaction with
9. Test competing implementations
Current Conformance Level / Target Conformance Level
Extensive
Yes or No (briefly summarize)
Were competing implementations tested? Yes
Did this lead to model refinement or improvement? yes
10. Conform to standards
Current Conformance Level / Target Conformance Level
Partial
Yes or No (briefly summarize)
Are there operating procedures, guidelines, or standards for this type of multiscale modeling? Yes
How do your modeling efforts conform? Currently writing ODD Protocol