Investigators
James Schwaber and Rajanikanth Vadigepalli
Contact info (email)
rajanikanth.vadigepalli@jefferson.edu
1. Define context(s)
reveal new biological insights
Current Conformance Level / Target Conformance Level
Adequate
Primary goal of the model/tool/database
This project is focused on developing a multiscale model of how the heart is controlled by the neuronal circuits in the brainstem. Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. our prior analysis of brainstem neurons revealed that single-neuron transcriptional heterogeneity reflects an adaptive response to synaptic inputs and that these neurons organize into distinct subtypes with respect to synaptic inputs received. We utilized a multiscale model to examine the functional impact neuronal adaptation has on modulating autonomic activity, focusing on parasympathetic activity, within the context of short-term baroreceptor reflex regulation.
Biological domain of the model
baroreflex control of blood pressure
Structure(s) of interest in the model
brainstem; heart;
Spatial scales included in the model
molecular scale; cellular scale; organ scale
Time scales included in the model
milliseconds; seconds; minutes
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 | Journal peer review | Adequate | |
| ex vivo (excised tissues) | No | |||
| in vivo pre-clinical (lower-level organism or small animal) | Yes | Journal peer review | Adequate | |
| in vivo pre-clinical (large animal) | No | |||
| Human subjects/clinical | No | |||
| 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) | Yes | Journal peer review | Adequate | |
| 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 | Lab peers | Prior to manuscript submission | Independent cross-check starting with the manuscript | Adequate |
| Validation | Lab peers | Prior to manuscript submission | Independent cross-check starting with the manuscript | Adequate |
| Uncertainty quantification | Model developer | During modeling process | Established techniques | Adequate |
| Sensitivity analysis | Model developer | During modeling process | Established techniques | Adequate |
| 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 |
|---|---|---|---|
| Model limited to normal control of blood pressure; Disease states such as high blood pressure are not accounted for in the brainstem regulatory networks. | Cardiovascular disease researchers | Description in the publications | Adequate |
5. Version control
| Current Conformance Level / Target Conformance Level |
|---|
| Inadequate |
| Naming Conventions? | Repository? | Code Review? | |
|---|---|---|---|
| individual modeler | Yes | No | Independent peer cross-check |
| within the lab | Yes | No | Independent peer cross-check |
| collaborators | Yes | No | No |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | Adequate |
| Scope and intended use described? | Adequate |
| User’s guide? | Inadequate |
| Developer’s guide? | Inadequate |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | Shared folders; Lab presentations | Supplemental information in manuscripts | Manuscripts |
| Models | Shared folders; Lab presentations | Supplemental information in manuscripts | Manuscripts |
| Software | Shared folders; Lab presentations | NA | NA |
| Results | Shared folders; Lab presentations | Manuscripts | Manuscripts |
| Implications of results | Shared folders; Lab presentations | Manuscripts | Manuscripts; Institutional Newsletters |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Reviewer(s) name & affiliation: | Lab peers |
|---|---|
| When was review performed? | Prior to manuscript submission |
| How was review performed and outcomes of the review? | Independent review was performed starting with the description in the manuscript to develop new code according to the equations, parameter values, and contextual information provided in the manuscript. |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| 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 |
|---|
| Adequate |
| 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? | Yes |