Investigators
Caterina Stamoulis, Deniz Erdogmus, Theodoros Zanos, Min Zhang, Michael Miga
1. Define context(s)
aid in clinical decision making
aid in clinical trial design
identify/explore new therapies
reveal new biological insights
Primary goal of the model/tool/database
The goal of this resource is to develop a relatively generic framework that would allow preclinical experiments to inform clinical decision making. Unfortunately in the area of peripheral neuromodulation, it is not possible to do analogous modulation as one can do in the preclinical environment. The question this model-building framework is asking is, "Can human peripheral therapeutic stimulation be mapped to a preclinical system and produce an appropriate electrophysiological response which is subsequently mapped to an appropriate human electrophysiological response all done in silico with deterministic and machine learning models?" This framework would essentially functionalize the preclinical system as a forecaster/predictor of human response but me much better grounded than previous work. It could really break down barriers to neuromodulation therapy.
Biological domain of the model
Lungs and heart
Structure(s) of interest in the model
Vagal and phrenic nerves
Spatial scales included in the model
0.0001 m to 0.01m
Time scales included in the model
0.001 s to 1 s
Other uses for the model (optional)
Utlimately, if there was some success to this approach, it may lead to a means of differentiating which animals are particularly relevant for certain neuromoduation therapies.
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.) |
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| ex vivo (excised tissues) |
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| in vivo pre-clinical (lower-level organism or small animal) |
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| in vivo pre-clinical (large animal) |
Yes - feline, No - rat |
No -feline data is on Sparc Site, Yes - rat data is by collaborator |
Repeat experiments |
Adequate |
| Human subjects/clinical |
No |
Yes |
Population of patients |
Adequate |
| Other: ________________________ |
No, gross pathology of respective nerves |
Yes |
Multiple sample samples |
Adequate |
| Data for validating the model |
Published? |
Private? |
How is credibility checked? |
Current Conformance Level / Target Conformance Level |
| in vitro (primary cells cell, lines, etc.) |
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| ex vivo (excised tissues) |
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| in vivo pre-clinical (lower-level organism or small animal) |
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| in vivo pre-clinical (large animal) |
see above |
see above |
Leave one out validation |
Adequate |
| Human subjects/clinical |
see above |
see above |
Leave one out validation |
Adequate |
| Other: ________________________ |
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3. Validate within context(s)
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Who does it? |
When does it happen? |
How is it done? |
Current Conformance Level / Target Conformance Level |
| Verification |
Users |
Matching of electrophysiological responses |
Basic correlation of electrophysiolological response |
adequate |
| Validation |
Users |
Novel electrophysiological responses in response to recorded stimulation |
Basic correlation of electrophysiolological response |
adequate |
| Uncertainty quantification |
Comes naturally out of analysis |
Every time |
Likely over a population of responses to similar disease |
adequate |
| Sensitivity analysis |
Users |
When the system is probed for parameter variations |
With variations in stimulation, what is the deviation from electrophysiological response |
adequate |
| Other:__________ |
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| Additional Comments |
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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 |
| Until more data is acquired and analyzed with this framework in mind for development, it is likely that models built will be specific to this appliation. |
Research scientists primarily |
In publications |
Adequate |
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5. Version control
| Current Conformance Level / Target Conformance Level |
| Partial |
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Naming Conventions? |
Repository? |
Code Review? |
| individual modeler |
Yes |
Yes |
No |
| within the lab |
NA |
NA |
NA |
| collaborators |
NA |
NA |
NA |
6. Documentation
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Current Conformance Level / Target Conformance Level |
| Code commented? |
Partial due to early development |
| Scope and intended use described? |
Partial due to early development |
| User’s guide? |
Partial due to early development |
| Developer’s guide? |
Insufficient due to early development |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
| Adequate |
| Target Audience(s): |
“Inner circle” |
Scientific community |
Public |
| Simulations |
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Yes |
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| Models |
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Yes |
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| Software |
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Yes |
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| Results |
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Yes |
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| Implications of results |
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Framework to create cross species clinical tools |
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8. Independent reviews
| Current Conformance Level / Target Conformance Level |
| Insufficient, not built yet |
| Reviewer(s) name & affiliation: |
NA |
| When was review performed? |
NA |
| How was review performed and outcomes of the review? |
NA |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
| Partial, not built yet but in addition to presented pipeline, we are exploring adaptive/adversarial machine learning methods that will provide parallel feedback mechanisms |
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Yes or No (briefly summarize) |
| Were competing implementations tested? |
NA - not built yet |
| Did this lead to model refinement or improvement? |
NA - not built yet |
11. (optional) Additional information to support items 1-10
This project is a new conceptualization for the use of preclinical systems. To our knowledge, it has not been attempted. If successful, the framework would be quite useful to the community.
None