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62f58d8800001500 Insulin processing 1 Mouse

Let me review the GO-CAM model on insulin processing in mouse (gomodel:62f58d8800001500). I'll analyze its structure, biological accuracy, and adherence to GO-CAM best practices.

Model Overview

This is a production-status GO-CAM model titled "Insulin processing 1 (Mouse)" for the taxon Mus musculus (NCBITaxon:10090). It represents the insulin processing pathway, with 11 molecular activities connected through causal associations.

Biological Content Assessment

Pathway Structure

The model represents insulin processing, focusing on: 1. Protein disulfide bond formation in the ER (Ero1b, P4hb) 2. Zinc transport (Slc30a8, Slc30a5, Slc30a3) 3. Proteolytic processing of proinsulin (Pcsk1, Pcsk2, Cpe) 4. Insulin zinc binding (Ins2) 5. Protein folding (Hsp90b1)

The causal flow appears logical, connecting activities in a way that reflects the biological process of insulin maturation from the ER through secretory granules.

Evidence Quality

The model uses appropriate evidence codes: - ECO:0000315 (mutant phenotype evidence) - ECO:0000314 (direct assay evidence) - ECO:0000316 (genetic interaction evidence) - ECO:0000266 (sequence orthology evidence)

Each activity is supported by evidence from published literature.

GO-CAM Best Practices Assessment

Positive Aspects

  1. Appropriate cellular locations: Activities are annotated with proper cellular compartments (ER lumen, secretory granule, Golgi membrane)
  2. Consistent causal relationships: Uses appropriate causal predicates (RO:0002413 "provides input for", RO:0002629 "directly positively regulates")
  3. Comprehensive representation: All key steps in insulin processing are included
  4. Species-specific model: Correctly uses mouse gene identifiers (MGI)
  5. Well-supported with evidence: All activities have literature references

Areas for Improvement

  1. Missing evidence for some causal associations: Several causal associations have empty evidence arrays, including:
  2. From Pcsk1 to Cpe
  3. From Cpe to PC2
  4. From PC2 to Cpe
  5. From Cpe to Slc30a8
  6. From Hsp90b1 to P4hb

  7. From Slc30a5 to Ins2

  8. Incomplete activity connections: Slc30a3 (zinc transporter) is part of the insulin processing but has no causal connections to other activities

  9. Lack of complex representation: The model appears to involve protein interactions but doesn't explicitly represent any complexes, which might be appropriate based on the "How to annotate complexes in GO-CAM" guidelines if the activities are carried by individual proteins rather than complexes.

Specific Gene Function Validation

Let me look at some of the key protein roles in the model:

  1. Ins2 (MGI:MGI:96573) - annotated with zinc ion binding (GO:0008270) in insulin processing (GO:0030070), which is consistent with the known role of insulin binding zinc ions during maturation and storage.

  2. Slc30a8 (MGI:MGI:2442682) - annotated with zinc ion transmembrane transporter activity (GO:0005385) in secretory granule membrane (GO:0030667), which is accurate as this zinc transporter is known to be important for insulin packaging and secretion.

  3. P4hb (MGI:MGI:97464) - protein disulfide isomerase with reductase activity (GO:0015035) in ER lumen (GO:0005788), which is appropriate for its role in insulin folding.

Recommendations for Improvement

  1. Add evidence for all causal relationships: Every causal association should have supporting evidence.

  2. Complete the causal connections for Slc30a3: This zinc transporter (MGI:MGI:1345280) should be causally connected to the pathway if it plays a role in insulin processing.

  3. Consider annotation of potential complexes: If any of these proteins function as complexes during insulin processing, consider using the complex annotation guidelines to represent them appropriately.

  4. Verify the exact order of processing events: Ensure the causal flow accurately reflects the temporal sequence of insulin processing from synthesis through maturation.

Conclusion

Overall, this is a well-constructed GO-CAM model that accurately represents insulin processing in mouse. It follows most GO-CAM best practices, has good evidence support, and represents the biological process in a clear and logical manner. The main improvement would be adding evidence for all causal associations and connecting all activities properly within the pathway.

The model is available at: https://bioregistry.io/go.model:62f58d8800001500