Investigators
Xiaobo Zhou; Yunzhi Yang
Contact info (email)
xiaobo.zhou@uth.tmc.edu
1. Define context(s)
aid in clinical trial design
reveal new biological insights
Current Conformance Level / Target Conformance Level
Adequate
Primary goal of the model/tool/database
BoneLineage is a Matlab program developed to simulate the bone stem cell lineage process under various growth factor treatment regimens. Briefly, the molecular (mRNA and RPPA) and cellular data (dsDNA, ALP and ARS) are collected experimentally for constructing and calibrating the multiscale model of BMSC lineage commitment. The molecular and cellular components were implemented by separate ODE systems. The model was validated by additional group of experimental data. The parameters were estimated by an open tool mcmcstat.
Biological domain of the model
Stem cell differentiation
Structure(s) of interest in the model
Stem cell/growth factor-loaded scaffold
Spatial scales included in the model
molecular, cell and tissue
Time scales included in the model
seconds to weeks
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 | No | expert review | extensive |
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | no | yes | internal evaluation | insufficient |
| 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.) | Yes | no | expert review | partial |
| 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 | Project team | continuously | automated test suites | partial |
| Validation | Project team | continuously | manual comparisons | partial |
| Uncertainty quantification | Project team | future work | NA | NA |
| Sensitivity analysis | Project team | 2017 | perturbation analysis | 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 |
|---|---|---|---|
| Immunity reaction | All potential users of the model | Will be stated with model dissemination | partial |
| Mechanical stress | All potential users of the model | Will be stated with model dissemination | partial |
| Nerve growth | All potential users of the model | Will be stated with model dissemination | partial |
| Parameter joint optimization issue | All potential users of the model | Will be stated with model dissemination | insufficient |
5. Version control
| Current Conformance Level / Target Conformance Level |
|---|
| Partial |
| Naming Conventions? | Repository? | Code Review? | |
|---|---|---|---|
| individual modeler | yes | yes | yes |
| within the lab | yes | yes | yes |
| collaborators | yes | yes | yes |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | extensive |
| Scope and intended use described? | adequate |
| User’s guide? | adequate |
| Developer’s guide? | insufficient |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| partial |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | institutional file drive | open code | https://sites.google.com/site/bonelineagesimulator/ |
| Models | institutional file drive | IMAG MSM; publication | https://www.nature.com/articles/s41536-017-0009-0 |
| Software | institutional file drive | open code | https://sites.google.com/site/bonelineagesimulator/ |
| Results | institutional file drive | IMAG MSM; publication | https://www.nature.com/articles/s41536-017-0009-0 |
| Implications of results | institutional file drive | IMAG MSM; publication | https://www.nature.com/articles/s41536-017-0009-0 |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| partial |
| Reviewer(s) name & affiliation: | blind review |
|---|---|
| When was review performed? | 2017 |
| How was review performed and outcomes of the review? | accepted for publication in npj |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| Partial |
| Yes or No (briefly summarize) | |
|---|---|
| Were competing implementations tested? | Yes Perturbation on parameters and input and rerun the model |
| Did this lead to model refinement or improvement? | Yes Optimized parameters leads to better fitting and prediction performance |
10. Conform to standards
| Current Conformance Level / Target Conformance Level |
|---|
| insufficient |
| Yes or No (briefly summarize) | |
|---|---|
| Are there operating procedures, guidelines, or standards for this type of multiscale modeling? | Not yet |
| How do your modeling efforts conform? | We intend to generate multi-scale and multi-model for validation |
11. (optional) Additional information to support items 1-10
Model dissemination
The paper of bone stem lineage model (npj Regenerative Medicine) has been cited by 5 independent institutions. The online simulation software BoneLineageSimulator (googlesites 2019) has been accessed intensively. We received users feedback and consultant from two groups.