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Based on my review of the GO-CAM model 6690711d00002904 and the related information, I'll now provide a comprehensive review:

Review of GO-CAM Model 6690711d00002904

Model Overview

This GO-CAM model (gomodel:6690711d00002904) represents the "L-histidine biosynthetic process" (GO:0000105) in Schizosaccharomyces pombe (fission yeast). The model captures the enzymatic steps of the histidine biosynthesis pathway with multiple gene products performing specific molecular functions that are causally connected to create a coherent representation of the pathway.

Model Structure and Content

The model includes 8 activities representing the enzymatic steps of histidine biosynthesis:

  1. ATP phosphoribosyltransferase (his1) - PomBase:SPAC25G10.05c (GO:0003879)
  2. Phosphoribosyl-ATP diphosphatase (his7) - PomBase:SPBC29A3.02c (GO:0004636)
  3. Phosphoribosyl-AMP cyclohydrolase (his7) - PomBase:SPBC29A3.02c (GO:0004635)
  4. 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide isomerase (his6) - PomBase:SPAC3F10.09 (GO:0003949)
  5. Imidazoleglycerol-phosphate synthase (his4) - PomBase:SPBC418.01c (GO:0000107)
  6. Imidazoleglycerol-phosphate dehydratase (his5) - PomBase:SPBC21H7.07c (GO:0004424)
  7. Histidinol-phosphate transaminase (his3) - PomBase:SPBC11B10.02c (GO:0004400)
  8. Histidinol-phosphatase (SPCC1672.01) - PomBase:SPCC1672.01 (GO:0004401)
  9. Histidinol dehydrogenase (his2) - PomBase:SPBC1711.13 (GO:0004399)

All of these activities are annotated to occur in the cytosol (GO:0005829) and are part of the L-histidine biosynthetic process (GO:0000105).

Pathway Flow and Causal Connections

The model effectively uses the causal relationship predicate "provides input for" (RO:0002413) to connect the activities in the correct sequential order, representing the flow of metabolites through the pathway:

  1. his1 (ATP phosphoribosyltransferase) → his7 (Phosphoribosyl-ATP diphosphatase)
  2. his7 (Phosphoribosyl-ATP diphosphatase) → his7 (Phosphoribosyl-AMP cyclohydrolase)
  3. his7 (Phosphoribosyl-AMP cyclohydrolase) → his6 (1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide isomerase)
  4. his6 → his4 (Imidazoleglycerol-phosphate synthase)
  5. his4 → his5 (Imidazoleglycerol-phosphate dehydratase)
  6. his5 → his3 (Histidinol-phosphate transaminase)
  7. his3 → SPCC1672.01 (Histidinol-phosphatase)
  8. SPCC1672.01 → his2 (Histidinol dehydrogenase)

The final product of the pathway is correctly annotated as L-histidine (CHEBI:15971).

Evidence and References

The model is well supported by evidence:

  1. Multiple empirical evidence codes are used, including:
  2. ECO:0000316 (genetic interaction evidence)
  3. ECO:0000304 (author statement with traceable reference)
  4. ECO:0000315 (mutant phenotype evidence)
  5. ECO:0000266 (sequence orthology evidence)

  6. ECO:0000318 (biological aspect of ancestor evidence)

  7. Key references include:

  8. PMID:8299169 - Specific reference for his7 function
  9. PMID:8159167 - Evidence for his3 function
  10. PMID:16823372 - Evidence for subcellular localization in the cytosol
  11. PMID:15704224 - Evidence for his2 function
  12. PMID:17248775 - Additional evidence for his2 function

Quality Assessment

Strengths:

  1. Completeness: The model captures all the major steps in the histidine biosynthesis pathway with appropriate enzyme functions.

  2. Correct cellular location: All activities are properly located in the cytosol (GO:0005829), which is consistent with current knowledge about histidine biosynthesis in yeast.

  3. Appropriate causal relationships: The causal flow is well represented using the "provides input for" relationship (RO:0002413), correctly showing the sequential steps in the pathway.

  4. Evidence quality: The model uses appropriate evidence codes and references, including experimental evidence where available.

  5. Bifunctional enzyme representation: The bifunctional nature of the his7 gene product is correctly represented with two distinct activities (phosphoribosyl-ATP diphosphatase and phosphoribosyl-AMP cyclohydrolase).

  6. Input/output annotations: The model correctly includes the substrate input (CHEBI:73183, 1-(5-phospho-beta-D-ribosyl)-ATP) and final product (CHEBI:15971, L-histidine).

Minor Issues:

  1. Redundant causal connection: There appears to be a duplicated causal relationship from his4 (PomBase:SPBC418.01c) to his5 (PomBase:SPBC21H7.07c) - this redundancy should be removed to maintain model parsimony.

  2. Missing evidence: One causal association (from his3 to SPCC1672.01) lacks evidence annotation.

  3. Nomenclature consistency: Gene naming is consistent (using his1-7), but SPCC1672.01 lacks a standard gene name, which slightly reduces model clarity.

Recommendations

  1. Remove the redundant causal relationship between his4 and his5.

  2. Add appropriate evidence for the causal association between his3 and SPCC1672.01.

  3. Verify if SPCC1672.01 has an assigned gene name (possibly his8 or his9) for consistency.

  4. Consider adding additional regulatory information if available, such as feedback inhibition of his1 by histidine, which is a common regulatory feature in histidine biosynthesis.

Conclusion

Overall, this GO-CAM model is a high-quality representation of the L-histidine biosynthetic process in Schizosaccharomyces pombe. It accurately captures the enzymatic steps, molecular functions, cellular locations, and pathway structure in accordance with established biological knowledge. The model demonstrates proper use of GO-CAM conventions and is well-supported by evidence. With the minor improvements suggested above, this model would serve as an excellent reference for the histidine biosynthesis pathway in fission yeast.