Modeling Multiscale Control of Liver Regeneration

Investigators
Rajanikanth Vadigepalli and Jan Hoek
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

Modeling the molecular and cellular interaction network controlling regeneration response to liver injury. The present model of liver regeneration was designed to combine disparate data sets from multiple liver cell types towards an integrative, quantitative accounting of the overall liver regeneration process. Recent results from single cell gene and protein regulation studies are starting to uncover the previously under-appreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges.

Biological domain of the model
liver regeneration
Structure(s) of interest in the model
liver; hepatocytes; hepatic stellate cells; liver resident macrophages; liver sinusoidal cells
Spatial scales included in the model
molecular scale; cellular scale; liver lobule (tissue) scale;
Time scales included in the model
seconds; minutes; hours; 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 Journal peer review Adequate
ex vivo (excised tissues) Yes Journal peer review Adequate
in vivo pre-clinical (lower-level organism or small animal) Yes Journal peer review Adequate
in vivo pre-clinical (large animal) No No
Human subjects/clinical No N0
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) No No
Human subjects/clinical No No
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 resection injury response Liver 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? Indequate
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