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Based on my review of the GO-CAM model "Insulin-like growth factor receptor signaling pathway 4 (Mouse)" with ID gomodel:62f58d8800000378 and the best practice guidelines, I can provide the following assessment:

GO-CAM Review: Insulin-like growth factor receptor signaling pathway 4 (Mouse)

Model Overview

This GO-CAM model represents the insulin-like growth factor receptor signaling pathway in mouse (Taxon: NCBITaxon:10090). The model captures a signaling cascade starting with IGF2 (Igf2 Mmus) as a ligand binding to and activating the IGF1 receptor (Igf1r Mmus), leading to activation of downstream components including IRS1, PI3K (Pik3r1 and Pik3ca), PDPK1, and AKT1.

Strengths

  1. Proper causal relationships: The model correctly uses the RO:0002629 (directly positively regulates) predicate to connect activities in a signaling cascade, which aligns with GO-CAM best practices.

  2. Appropriate molecular functions: Each protein has been assigned appropriate molecular functions:

  3. Igf2: receptor ligand activity (GO:0048018)
  4. Igf1r: insulin-like growth factor receptor activity (GO:0005010) and protein tyrosine kinase activity (GO:0004713)
  5. Irs1: transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068)
  6. Pik3r1: kinase activator activity (GO:0019209)
  7. Pik3ca: 1-phosphatidylinositol-3-kinase activity (GO:0016303)
  8. Pdpk1: 3-phosphoinositide-dependent protein kinase activity (GO:0004676)

  9. Akt1: protein serine kinase activity (GO:0106310)

  10. Evidence citations: Most activities are supported by appropriate evidence and literature citations.

  11. Biological process context: All activities are correctly placed in the context of the "insulin-like growth factor receptor signaling pathway" (GO:0048009).

  12. Small molecule handling: The model appropriately captures ATP and ADP as inputs and outputs for the Igf1r receptor activity.

Areas for Improvement

  1. Missing cellular component context: According to the signaling receptor activity annotation guidelines, activities should include cellular component information (e.g., 'occurs in' plasma membrane for transmembrane receptors). This information is missing for all activities in the model.

  2. Evidence for causal relationships: While most molecular functions have evidence, some causal associations lack evidence codes and citations. Specifically:

  3. The causal association between Igf1r protein tyrosine kinase activity and Irs1 adaptor activity has evidence, but several other causal relationships don't.

  4. The final activity (Akt1 serine kinase activity) has no outgoing causal associations, which is fine if it's the endpoint of this model.

  5. Missing has_input relations: According to the signaling receptor guidelines, a receptor should have the "effector protein it regulates" as its input using the 'has_input' relation. This is missing for some steps in the pathway.

  6. Missing evidence: The GO:0106310 (protein serine kinase activity) assigned to Akt1 has no evidence citation.

Recommendations

  1. Add cellular component annotations to activities, particularly for membrane proteins like IGF1R.

  2. Add evidence citations for all causal associations to strengthen the model's evidential support.

  3. Review and add missing has_input relations where appropriate according to the guidelines.

  4. Add evidence for the Akt1 protein serine kinase activity.

  5. Consider whether there are any additional steps in the pathway that could be added to make the model more comprehensive, if supported by evidence.

Overall, this is a well-constructed GO-CAM model that accurately represents the insulin-like growth factor receptor signaling pathway according to most GO-CAM best practices. The improvements suggested would enhance the model's compliance with guidelines and provide more complete information about the cellular locations and evidence base.

Link to this model: https://bioregistry.io/go.model:62f58d8800000378