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Based on my review of the GO-CAM model "Tricarboxylic acid cycle 1 (Mouse)" (gomodel:633b013300000306) and the best practice guidelines, here's my assessment:

Review of GO-CAM Model: Tricarboxylic acid cycle 1 (Mouse)

Model Overview

This model captures the tricarboxylic acid (TCA) cycle in mouse, representing the sequence of enzyme activities that make up this metabolic pathway. The model includes all key enzymes in the cycle, their molecular functions, inputs/outputs, cellular locations, and causal relationships.

Strengths of the Model

  1. Complete pathway representation: The model captures all the major enzymatic steps of the TCA cycle, with appropriate molecular functions assigned to each enzyme or enzyme complex.

  2. Complex representation: The model correctly uses protein complexes (e.g., isocitrate dehydrogenase complex, succinate dehydrogenase complex) with their component subunits listed, following the best practices for complex annotation in GO-CAM.

  3. Evidence and literature support: Each activity is supported by appropriate literature references with evidence codes (e.g., ECO:0000314 for direct assay evidence, ECO:0000315 for mutant phenotype evidence).

  4. Subcellular localization: The activities are appropriately localized to the mitochondrial matrix (GO:0005759) or mitochondrion (GO:0005739), consistent with the known location of the TCA cycle.

  5. Input/output molecules: The model clearly specifies the chemical inputs and outputs for each reaction using REACTO identifiers for metabolites.

  6. Causal connections: The model uses RO:0002413 ("provides input for") to show the sequential flow of the TCA cycle reactions.

  7. Regulatory component: The model includes a regulatory element with Sirt3 (MGI:MGI:1927665) protein deacetylase activity positively regulating succinate dehydrogenase activity.

Suggestions for Improvement

  1. Automated changes: The model includes comments about automated changes to some GO terms (GO:0005962 replaced by GO:0045242 and GO:0045257 replaced by GO:0045273). This is good practice for documenting term updates.

  2. Cellular compartment annotation: While most activities are correctly annotated to occur in the mitochondrial matrix (GO:0005759), the activity for MGI:MGI:1927665 (Sirt3) lacks a cellular location annotation. Consider adding this for completeness.

  3. Biological process annotation: Some activities are missing explicit "part_of" associations to the TCA cycle (GO:0006099). For consistency, consider adding this to all activities.

  4. Evidence for causal relationships: While the causal relationships between sequential enzyme activities use RO:0002413 ("provides input for"), many lack evidence annotations. Consider adding evidence for these connections.

  5. Regulatory mechanism details: The regulatory relationship between Sirt3 and the succinate dehydrogenase complex uses RO:0002629 ("directly positively regulates") with appropriate evidence, but the mechanism could be elaborated further. Does Sirt3 deacetylate a specific subunit of the complex?

Compliance with GO-CAM Best Practices

The model follows GO-CAM best practices by: - Using appropriate molecular function terms - Correctly representing protein complexes with their components - Using proper causal relationships between activities - Including evidence codes and literature references - Specifying inputs and outputs for reactions

Conclusion

This is a well-constructed GO-CAM model that effectively represents the mouse TCA cycle. It correctly represents the enzymatic activities, their physical connectivity through metabolites, and includes regulatory components. The minor suggestions above would further enhance the completeness and connectivity of the model, but overall, the model meets GO-CAM standards and accurately represents the biology of the TCA cycle.

The model can be viewed at: https://bioregistry.io/go.model:633b013300000306