Investigators
Qing Nie
Contact info (email)
qnie@uci.edu
1. Define context(s)
reveal new biological insights
Current Conformance Level / Target Conformance Level
Extensive
Primary goal of the model/tool/database
La Manno et al. used a linear model to relate abundance of pre-mRNA U(t) with abundance of mature mRNA S(t) (La Manno et al., Nature 2018). Given that the molecular regulatory mechanisms between pre-mRNA and mature mRNA are complicated, and in many molecular networks more commonly we observe non-linear (e.g. switch-like) responses, we proposed a nonlinear model of RNA velocity for the effects of pre-mRNA on the abundance of mature mRNA based on Michaelis–Menten kinetics.
Biological domain of the model
RNA velocity for scRNA-seq data
Structure(s) of interest in the model
Temporal trajectory in scRNA-seq data
Spatial scales included in the model
cellular to 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.) | ||||
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | Yes | No | The model was built in an unsupervised way on unbiased single-cell RNA sequencing data and spatial data. | 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) | Yes | No | By comparing to existing knowledge. | 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 | Students/postdocs/investigators | Throughout the project | The convergence of the algorithm is guaranteed. The method is tested on synthetic datasets. | Extensive |
| Validation | Students/postdocs/investigators | As the unsupervised model was established | The inferred developmental trajectory agrees with available knowledge. | Extensive |
| Uncertainty quantification | ||||
| Sensitivity analysis | Students/postdocs/investigators | As the unsupervised model was established | By tuning key parameters and comparing to annotated data. | 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 |
|---|---|---|---|
| Technical noise of scRNA-seq data | Scientific community who intends to apply this method to raw scRNA-seq data. | In discussion of the paper. | Adequate |
5. Version control
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Naming Conventions? | Repository? | Code Review? | |
|---|---|---|---|
| individual modeler | Yes | Yes | Peer |
| within the lab | Yes | Yes | Peer |
| collaborators | Yes | Yes | Peer |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | Extensive |
| Scope and intended use described? | Extensive |
| User’s guide? | Extensive |
| Developer’s guide? | Partial |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | |||
| Models | |||
| Software | R package: https://github.com/sqjin/nlvelo | R package: https://github.com/sqjin/nlvelo | |
| Results | Shared folders | Paper and tutorials | |
| Implications of results |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| Insufficient |
| Reviewer(s) name & affiliation: | |
|---|---|
| When was review performed? | |
| How was review performed and outcomes of the review? |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Yes or No (briefly summarize) | |
|---|---|
| Were competing implementations tested? | Yes. The advantage of the proposed method was demonstrated by comparing to the standard linear RNA velocity model. |
| 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. There are several standard procedures for preprocessing scRNA-seq data. |
| How do your modeling efforts conform? | Common data preprocessing procedures are followed. |