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Based on my review of the GO-CAM model and relevant guidelines, I will provide a comprehensive assessment of the "Insulin-like growth factor receptor signaling pathway 2 (Mouse)" model (gomodel:62e3212700000469).

GO-CAM Review: Insulin-like growth factor receptor signaling pathway 2 (Mouse)

Model Overview

This GO-CAM represents the insulin-like growth factor receptor (IGF1R) signaling pathway in mouse, featuring key components of the pathway starting from IGF2 ligand, through IGF1R receptor activation, and the downstream MAP kinase cascades.

Strengths of the Model

  1. Appropriate pathway representation: The model correctly captures the signaling cascade from the IGF2 ligand to downstream MAP kinase components, following the expected flow of a receptor tyrosine kinase signaling pathway.

  2. Causal relationships: The model correctly uses the "directly positively regulates" (RO:0002629) predicate consistently for causal associations between molecular activities.

  3. Detailed MAP kinase cascade: The model appropriately represents multiple levels of the MAP kinase cascade (MAP3K → MAP2K → MAPK).

  4. Evidence inclusion: Most activities have associated evidence with appropriate ECO codes and PMIDs.

  5. Molecular function terms: The model uses appropriate molecular function terms for each protein, such as receptor ligand activity (GO:0048018) for IGF2, and specific kinase activities for the kinases in the pathway.

Areas for Improvement

  1. Receptor-ligand relationship:
  2. The model shows IGF2 (receptor ligand activity) having a causal relationship to IGF1R (insulin-like growth factor receptor activity), which aligns with guidelines.

  3. However, IGF1R is shown with both receptor activity (GO:0005010) and protein tyrosine kinase activity (GO:0004713) represented as separate activities, creating redundancy. According to signaling receptor guidelines, these should be modeled as a single activity unit.

  4. Missing has_input relationship:

  5. For the IGF1R receptor activity (GO:0005010), there's correctly a has_input relationship to ATP and has_output to ADP.

  6. However, a has_input relationship to its immediately downstream target (in this case Shc1) should be present but is missing.

  7. Adaptor protein annotation:

  8. Grb2 is correctly annotated with "guanyl-nucleotide exchange factor adaptor activity" (GO:0005091)

  9. However, according to the "How to annotate molecular adaptors" guidelines, Grb2 should have "has_input" relationships to the molecules it brings together (likely Shc1 and Sos1), which are missing from the model.

  10. Evidence consistency:

  11. Some activities lack evidence, especially causal associations (For example, the causal association between MAP2K activities and MAPK activities).

  12. Where evidence is present, most use appropriate ECO codes, but some evidence statements could be strengthened with more specific references.

  13. BP context:

  14. All activities are correctly placed in the "insulin-like growth factor receptor signaling pathway" (GO:0048009), but more specific BP terms could potentially be used for some components.

  15. Cellular component context:

  16. The model lacks cellular component annotations, which would be useful to specify the localization of the activities (e.g., membrane localization for receptor activities).

Specific Recommendations

  1. Consolidate IGF1R activities: Consider merging the insulin-like growth factor receptor activity (GO:0005010) and protein tyrosine kinase activity (GO:0004713) of IGF1R into a single activity unit with both causal relationships, as these represent the same functional entity.

  2. Add missing has_input relationships:

  3. Add a has_input relationship from IGF1R receptor activity to Shc1

  4. Add has_input relationships for the adaptor protein Grb2 to show the molecules it's bringing together

  5. Complete evidence documentation:

  6. Add evidence annotations to the causal associations that currently lack them

  7. Ensure consistent use of ECO terms across all annotations

  8. Add cellular component information:

  9. Add "occurs in" plasma membrane for receptor activities

  10. Add appropriate cellular component terms for other activities in the cascade

  11. Verify completeness of branching:

  12. The model appears to represent multiple MAPK pathways (including MAPK1/3 and MAPK7), but ensure all relevant branches of the pathway are included

  13. Consider using complex terms: If any activities are carried out by protein complexes rather than individual proteins, it would be appropriate to use complex GO terms as outlined in the "How to annotate complexes in GO-CAM" guideline.

Conclusion

Overall, this is a well-constructed GO-CAM model that effectively represents the IGF receptor signaling pathway in mouse. The model follows most of the expected GO-CAM best practices and accurately depicts the biological relationships between the components. With the recommended improvements, particularly regarding input/output relationships for adaptor proteins and the consolidation of receptor activities, this model would provide an even more accurate and useful representation of the pathway.

You can view this model at: https://bioregistry.io/go.model:62e3212700000469