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67086be200002266 sphingolipid biosynthetic process GO 0030148

Based on my review of the GO-CAM model titled "sphingolipid biosynthetic process (GO:0030148)" (model ID: gomodel:67086be200002266), here is my assessment:

Overall Assessment

This model represents the sphingolipid biosynthetic pathway in Schizosaccharomyces pombe (fission yeast, taxon NCBITaxon:4896) and appears to be a comprehensive representation of the pathway components and their relationships. The model includes proteins involved in sphingolipid synthesis from initial steps (serine palmitoyltransferase activity) through ceramide synthesis and further modifications.

Strengths of the Model

  1. Comprehensive pathway representation: The model covers multiple aspects of sphingolipid biosynthesis including:
  2. Sphingosine biosynthesis
  3. Ceramide biosynthesis
  4. Inositol phosphoceramide synthesis

  5. Mannosylinositol phosphorylceramide synthesis

  6. Well-defined molecular functions: Each activity has appropriately assigned molecular functions with proper evidence codes.

  7. Cellular localization: Proper annotations for subcellular locations (primarily endoplasmic reticulum and Golgi) are included.

  8. Causal connections: The model uses appropriate causal relationships (RO:0002413 "provides input for") to link activities in the pathway.

  9. Input/output annotations: Chemical entities are properly linked as inputs and outputs of enzymatic activities.

Issues and Recommendations

  1. Complex representation: The model comment states: "Orm1, Sac11 and Sac12 are part of the Serine palmitoyltransferase complex, function unknown". However, these proteins are modeled individually without explicit representation of the complex. According to GO-CAM guidelines, if these form a functional complex but their specific activities are unknown, it might be better to use a GO complex ID to represent this.

  2. Undefined molecular function: Several proteins (SPAC3C7.01c/sac12, SPBC119.09c/orm1, SPBC36B7.02/svf2) have "GO:0003674" (molecular_function) as their activity, indicating unknown molecular function. This is acceptable given evidence limitations, but when possible, specific functions should be determined.

  3. Evidence consistency: Most activities have appropriate evidence codes, but there are a few instances of empty evidence lists (e.g., in causal_associations for activities gomodel:67086be200002266/67086be200002288, gomodel:67086be200002266/67086be200002404). These should be completed with appropriate evidence.

  4. Consistency in input/output: In some cases, like for activity gomodel:67086be200002266/67086be200002533 (SPAC17G8.11c/imt3), there are duplicate outputs (CHEBI:25168 mannosylinositol phosphorylceramide) and one output lacks evidence. This redundancy should be resolved.

  5. Potentially erroneous evidence: In gomodel:67086be200002266/67086be200002476 (SPBC36B7.02/svf2), there are evidence codes with "with_objects" references to "PomBa", "PomBas", and "PomBase" which appear to be incomplete or incorrect entries. These should be corrected to proper database references.

  6. Protein without specific annotation: The model includes a generic protein (CHEBI:36080) with N-acylsphingosine amidohydrolase activity (GO:0017040) but without evidence codes. This should be replaced with a specific protein if possible, or evidence should be added.

Technical Consistency

  1. The causal flow is generally well-represented with appropriate use of RO:0002413 (provides input for) and RO:0002629 (directly positively regulates) predicates.

  2. The usage of evidence codes is generally appropriate, with many annotations supported by experimental evidence (ECO:0000269), sequence orthology (ECO:0000266), and biological aspect of ancestor evidence (ECO:0000318).

Biological Consistency

The model accurately represents the sphingolipid biosynthetic pathway according to current knowledge: - Initial synthesis of 3-ketosphinganine from serine and palmitoyl-CoA - Reduction to sphinganine - Conversion to ceramides - Further modification of ceramides with inositol phosphate - Mannosylation of inositol phosphoceramides

The pathway flow is biologically consistent, and the localization of activities to appropriate subcellular compartments (ER and Golgi) matches known biology.

Recommendations for Improvement

  1. Consider using a GO complex term to represent the Serine palmitoyltransferase complex mentioned in the comments.

  2. Complete the missing evidence annotations for causal relationships.

  3. Remove duplicate chemical entity listings and ensure all have appropriate evidence.

  4. Fix the incorrect evidence with_objects references (PomBa, PomBas).

  5. Replace the generic protein (CHEBI:36080) with a specific protein if possible.

  6. Review and specify molecular functions for proteins currently annotated with GO:0003674 (molecular_function) if literature supports more specific activities.

Overall, this is a high-quality model that provides a comprehensive representation of sphingolipid biosynthesis in fission yeast, with only minor issues that should be addressed for completeness and consistency.