Skip to content

Based on my review of the GO-CAM model "gomodel:YeastPathways_PWY3O-20" representing folate polyglutamylation in Saccharomyces cerevisiae, I'll now provide a comprehensive assessment of the model's quality and adherence to GO-CAM best practices.

GO-CAM Review: Folate Polyglutamylation (gomodel:YeastPathways_PWY3O-20)

Overview

The model represents the folate polyglutamylation pathway in yeast (Saccharomyces cerevisiae), which is important for one-carbon metabolism. This pathway involves the addition of multiple glutamate molecules to folate derivatives, making them more effective coenzymes and preventing their efflux from cells.

Model Structure Assessment

Strengths:

  1. Comprehensive pathway representation: The model captures the key enzymatic activities in the folate polyglutamylation pathway, including dihydrofolate synthase (Fol3p/FOL3), dihydrofolate reductase (Dfr1p/DFR1), and folylpolyglutamate synthase (Met7p/MET7).

  2. Molecular details: The model appropriately includes input and output molecules for each reaction, including ATP, folate derivatives, glutamate, and other relevant metabolites.

  3. Subcellular localization: All activities are correctly annotated as occurring in the cytosol (GO:0005829), which is consistent with known folate metabolism in yeast.

  4. Biological process annotation: All activities are appropriately linked to the folate metabolic process (GO:0046655).

  5. Evidence capture: Each annotation includes evidence codes (ECO:0000313) and references to the source pathway (SGD_PWY:PWY3O-20).

Areas for Improvement:

  1. Limited causal relationships: Only two activities (dihydrofolate synthase and dihydrofolate reductase) have causal relationships defined using RO:0002411 (causally upstream of). The model would better represent the pathway flow if causal relationships were added between all sequential steps.

  2. Missing activity connections: Several enzymatic steps are not causally linked, making it difficult to interpret the flow of the pathway. For example, there are no causal connections between many of the folylpolyglutamate synthase (Met7p) activities.

  3. Redundant activity annotations: The model contains multiple instances of the same enzyme activities (e.g., multiple nodes for folylpolyglutamate synthase activity by MET7/SGD:S000005767) that appear to represent different reaction instances but aren't clearly distinguished in their roles.

  4. No regulatory relationships: The model lacks any regulatory relationships (using RO:0002629 or RO:0002630), which might be important for understanding pathway control.

Technical Content Assessment

  1. Gene product annotation: The model correctly uses SGD identifiers for yeast proteins (e.g., SGD:S000005767 for Met7p).

  2. Chemical entities: The model uses appropriate ChEBI identifiers for all small molecules.

  3. Evidence codes: The model consistently uses ECO:0000313 (imported information used in automatic assertion) with appropriate provenance tracking.

  4. Biological alignment: The enzymatic activities in the model align with the known biochemistry of folate polyglutamylation in yeast, as confirmed by literature and SGD pathway resources.

Recommendations for Improvement

  1. Add causal connections: Connect all activities in the pathway with appropriate causal relationships (RO:0002411 - causally upstream of) to show the flow of the pathway.

  2. Clarify redundant activities: Either consolidate redundant activities or clearly differentiate their specific roles in the pathway (e.g., different substrates or products).

  3. Consider adding regulatory relationships: If known from literature, include any regulatory relationships that affect the pathway.

  4. Add more specific evidence: Consider strengthening evidence by including specific experimental references beyond the general pathway citation.

  5. Improve model parsimony: The current model has some redundancy in representation. A more streamlined model with clearer causal connections would improve human readability while maintaining biological accuracy.

Conclusion

The GO-CAM model "gomodel:YeastPathways_PWY3O-20" provides a good representation of the folate polyglutamylation pathway in yeast. It includes the key enzymatic activities, molecular inputs/outputs, and correct subcellular localization. The main areas for improvement involve enhancing the causal connections between activities to better represent pathway flow and reducing redundancy in activity representation. With these improvements, the model would provide a more complete and easier-to-interpret representation of this important metabolic pathway.