Based on my review of the GO-CAM model "66a3e0bb00001036" titled "IGF1-mediated signaling via IGF1R receptor (Human)", I will now provide a comprehensive analysis of the model against GO-CAM best practices.
GO-CAM Model Review: gomodel:66a3e0bb00001036¶
Summary¶
This model represents IGF1-mediated signaling via the IGF1R receptor in humans. It includes four key activities: 1. IGF1R receptor activity (enabled by P08069/IGF1R) 2. IRS1 signaling adaptor activity (enabled by P35568/IRS1) 3. IRS2 signaling adaptor activity (enabled by Q9Y4H2/IRS2) 4. IGF1 growth factor activity (enabled by P05019/IGF1)
Strengths¶
- The model correctly depicts the signaling cascade from IGF1 to IGF1R to downstream adaptors (IRS1 and IRS2)
- All activities are grounded in appropriate evidence and references (PMIDs)
- The model uses appropriate causal relationships (RO:0002629 "directly positively regulates")
- Activities are correctly linked to appropriate cellular locations
- The model incorporates the correct biological process (GO:0048009 "insulin-like growth factor receptor signaling pathway")
Areas for Improvement¶
1. Molecular Function Annotations¶
The signaling adaptor activities for IRS1 and IRS2 are both annotated with GO:0035591 "signaling adaptor activity", which is correct. However, according to the "How to annotate molecular adaptors" document, adaptors should have "has input" relationships to the molecules they bring together. In this model:
- Both IRS1 and IRS2 should have "has input" relationships to their binding partners
- According to the literature you provided, IRS1 and IRS2 bind to both IGF1R and downstream effectors like PI3K
2. Downstream Signaling Pathway Representation¶
The model stops at IRS1/IRS2 and doesn't represent further downstream signaling, such as: - PI3K pathway activation (mentioned in the literature) - MAPK pathway activation - AKT signaling
These pathways are well-established in IGF1 signaling based on the provided literature, particularly evident in PMID:16878150 and PMID:17827393.
3. IGF1 and IGF1R Relationship¶
According to the "Signaling receptor activity annotation guidelines", the relationship between IGF1 (ligand) and IGF1R (receptor) should be modeled as: - IGF1 "directly positively regulates" IGF1R (which is currently represented correctly) - IGF1 should have a GO:0048018 or child term (receptor ligand activity) - The model correctly uses GO:0008083 "growth factor activity" which is appropriate for IGF1
4. Additional Context¶
The model could benefit from adding: - Phosphorylation events (tyrosine phosphorylation of IRS1/IRS2) - Representation of PI3K (PIK3R1) which is a key binding partner of IRS1/IRS2 - The subcellular location for IRS1 and IRS2 is cytoplasm (GO:0005737), which is correct but could be more specific based on the literature
Technical Accuracy¶
The evidence codes used in the model are appropriate: - ECO:0000314 (direct assay evidence used in manual assertion) - ECO:0000305 (curator inference used in manual assertion) - ECO:0000250 (sequence similarity evidence used in manual assertion with UniProtKB:P35569) - ECO:0000353 (physical interaction evidence used in manual assertion)
The overall causal flow is biologically accurate, representing: 1. IGF1 → IGF1R 2. IGF1R → IRS1 and IRS2
Conclusion¶
This GO-CAM model provides a good foundation for representing IGF1 signaling through IGF1R, IRS1, and IRS2. It captures the core interactions accurately but could be expanded to include:
- Explicit "has input" relationships for IRS1 and IRS2 adaptors
- Downstream signaling events (PI3K/AKT, MAPK pathways)
- Phosphorylation events that are key to this signaling cascade
- Additional binding partners like PIK3R1 (p85 subunit of PI3K)
The model is consistent with current biological knowledge about IGF1 signaling and follows most GO-CAM best practices. With the suggested improvements, it would provide a more comprehensive representation of this important signaling pathway.