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
other
Current Conformance Level / Target Conformance Level
Adequate / 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.
Both the modeling and the biological contexts are clearly defined by the specifications in the model description.
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 / Extensive | |
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | Yes | Flow cytometry;staining | Extensive / Extensive | |
| in vivo pre-clinical (large animal) | ||||
| Human subjects/clinical | ||||
| Other: ________________________ | The model development is driven by two types of data and information, literature-based, as well as data collected specifically for this project, ranging from molecular data for the intracellular models to whole lung and blood measurements for the other scales, used to construct and validate the component models. Furthermore, we are currently designing an in vivo mouse experiment that will provide data simultaneously for the different scales involved, in order to validate the overall integrated model. |
| 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: ________________________ | The model development is driven by two types of data and information, literature-based, as well as data collected specifically for this project, ranging from molecular data for the intracellular models to whole lung and blood measurements for the other scales, used to construct and validate the component models. Furthermore, we are currently designing an in vivo mouse experiment that will provide data simultaneously for the different scales involved, in order to validate the overall integrated model. |
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 / Extensive | |
| Validation | Borna Mehrad | When data becomes available | Mouse models; histopathology | Extensive / Extensive |
| Uncertainty quantification | ||||
| Sensitivity analysis | Reinhard Laubenbacher's lab | Continuously | Extensive / Extensive | |
| Other:__________ | ||||
| Additional Comments | The model, once complete, will be evaluated within the context of a well-characterized, appropriate animal model, specifically developed by one of the collaborating laboratories for the study of invasive aspergillosis. Data from in vivo experiments are being used for model validation. Within this context, uncertainty quantification is not feasible. | Extensive / Extensive |
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 / Extensive |
| Some innate immune cell types missing | Everyone | Documentation | Extensive / Extensive |
| Limited to iron mediated mechanisms | Everyone | Documentation | Extensive / Extensive |
| Lack of detailed mechanisms for the role of the liver in the host response, as well as the lack of mechanisms for epithelial and endothelial cells. These are represented by simple phenomenological models. | Everyone | Documentation | Extensive / Extensive |
5. Version control
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive / Extensive |
| Naming Conventions? | Repository? | Code Review? | |
|---|---|---|---|
| individual modeler | Diverse--depending on component models | Github and web-based information management system (Girder) | Unit testing/continuous integration |
| within the lab | Diverse--depending on component models | Github and web-based information management system (Girder) | Unit testing/continuous integration |
| collaborators | Diverse--depending on component models | Github and web-based information management system (Girder) | Unit testing/continuous integration |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | Adequate. Documentation is ongoing. / Extensive |
| Scope and intended use described? | Partial / Extensive |
| User’s guide? | Partial / Comprehensive |
| Developer’s guide? | Partial / Extensive |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| Partial / Extensive |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | https://nutritionallungimmunity.org/;Github | https://nutritionallungimmunity.org/;Github;Presentations and publications | https://nutritionallungimmunity.org/;Github |
| Models | https://nutritionallungimmunity.org/;Github | https://nutritionallungimmunity.org/;Github;;Presentations and publications | https://nutritionallungimmunity.org/;Github |
| Software | https://nutritionallungimmunity.org/;Github | https://nutritionallungimmunity.org/;Github;;Presentations and publications | https://nutritionallungimmunity.org/;Github |
| Results | https://nutritionallungimmunity.org/;Github;;Presentations and publications | ||
| Implications of results | https://nutritionallungimmunity.org/;Github;;Presentations and publications |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive / Extensive |
| Reviewer(s) name & affiliation: | Filippo Castiglione Institute for Applied Computing of the Italian Research Council |
|---|---|
| When was review performed? | November 2019 |
| How was review performed and outcomes of the review? | Dr. F. Castiglione, an expert in agent-based modeling of the immune system visited in the fall of 2019, and reviewed various aspects of the model building with the entire project team. Based on some of his suggestions, we have modified some of our software implementations. |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| Partial / Extensive |
| Yes or No (briefly summarize) | |
|---|---|
| Were competing implementations tested? | The main focus of this project is on the development of a novel modular software architecture for multiscale agent-based models. In order to assess how this novel software design affects model performance, in particular whether it affects model dynamics and computational complexity, we will compare it to a model built with the same information, but using a “standard” software architecture, common for agent-based models. We are building both models side-by-side, so we can pinpoint differences as they arise. |
| Did this lead to model refinement or improvement? | Likely |
10. Conform to standards
| Current Conformance Level / Target Conformance Level |
|---|
| Partial / Adequate |
| Yes or No (briefly summarize) | |
|---|---|
| Are there operating procedures, guidelines, or standards for this type of multiscale modeling? | We are conforming to all applicable model and data standards, to the extent these are available. For instance, we are using the ODD protocol for the agent-based model component, something not commonly done in this field. We are also using workflow managers for analysis of bioinformatics pipelines for easier reproducibility. |
| How do your modeling efforts conform? | Writing an ODD protocol for the implementation of model |