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66187e4700002284 septation initiation signaling GO 0031028

Now that I have reviewed the main GO-CAM guidelines, I'll systematically review the model "gomodel:66187e4700002284" which represents the "septation initiation signaling (GO:0031028)" in fission yeast (NCBITaxon:4896).

GO-CAM Model Review: Septation Initiation Signaling

Model Overview

This GO-CAM model represents the septation initiation signaling (SIN) pathway in fission yeast (Schizosaccharomyces pombe). The SIN is a signaling cascade essential for coordinating cell division with mitosis, ensuring that cytokinesis occurs only after chromosome segregation.

Structure and Connectivity Analysis

The model has 27 activities represented, involving various proteins functioning in different cellular locations including spindle pole bodies (SPBs) and the actomyosin contractile ring. The key signaling cascade includes:

  1. Upstream regulators at the SPB (Plo1/Sid4/Cdc11)
  2. Core signaling pathway (Spg1/Cdc7/Sid1/Sid2)
  3. Regulatory components (GAPs like Cdc16/Byr4, phosphatases, etc.)

Connectivity strengths:

  • The model correctly represents the hierarchical structure of the SIN pathway
  • Causal relationships between activities are well-documented with appropriate evidence
  • The use of appropriate relation predicates (RO:0002629 "directly positively regulates", RO:0002630 "directly negatively regulates", etc.)

Notable pathway connections:

  • Appropriate representation of Spg1 GTPase as a central switch in the pathway
  • GAP proteins (Cdc16/Byr4) properly shown negatively regulating Spg1
  • The downstream kinase cascade (Cdc7 → Sid1 → Sid2) follows correct biological sequence

Issues Identified

  1. Missing molecular functions: Several proteins have GO:0003674 (molecular_function) listed, which is a placeholder for "unknown molecular function":
  2. PomBase:SPAC2C4.10c (csc4)
  3. PomBase:SPBC3H7.13 (csc1)
  4. PomBase:SPBC27B12.04c (csc2)
  5. PomBase:SPBC1773.01 (csc3)

  6. PomBase:SPAC1782.05 (ypa2)

  7. Missing evidence codes: Some causal associations lack evidence:

  8. The causal association between csc4 (SPAC2C4.10c) and ppa3 (SPAC22H10.04)
  9. The causal association between csc2 (SPBC27B12.04c) and ppa3 (SPAC22H10.04)

  10. The causal association between csc3 (SPBC1773.01) and ppa3 (SPAC22H10.04)

  11. Incomplete cellular context: While most activities have appropriate cellular locations, a few are missing contextual information about where the activity occurs.

  12. Evidence quality: Most associations use appropriate experimental evidence codes, but there are instances where stronger evidence could be used (like ECO:0000269 "experimental evidence used in manual assertion" instead of ECO:0000353 "physical interaction evidence").

Biological Consistency Review

The model accurately represents the current understanding of the SIN pathway in S. pombe as documented in the literature. Key components and interactions match with published research:

  1. The central role of Spg1 GTPase and its regulation by Byr4/Cdc16 GAP
  2. The activation of Cdc7 kinase by GTP-bound Spg1
  3. The downstream signaling through Sid1 and Sid2 kinases
  4. The roles of phosphatases (Clp1, Ppa3) in regulating the pathway
  5. The inhibitory role of Cdc2 (CDK) on specific SIN components

Adherence to GO-CAM Best Practices

  1. Molecular function annotations: Most proteins have appropriate molecular functions assigned (kinase activities, GTPase activities, etc.).

  2. Biological process annotations: Activities are appropriately placed within specific biological processes:

  3. GO:0031028 (septation initiation signaling)
  4. GO:0031030 (negative regulation of septation initiation signaling)

  5. GO:0031031 (positive regulation of septation initiation signaling)

  6. Cellular component annotations: Activities are correctly localized to relevant cellular structures:

  7. GO:0044732 (mitotic spindle pole body)
  8. GO:0071957 (old mitotic spindle pole body)
  9. GO:0071958 (new mitotic spindle pole body)

  10. GO:0110085 (mitotic actomyosin contractile ring)

  11. Evidence codes: The model generally uses appropriate evidence codes with PMIDs to support assertions.

Recommendations for Improvement

  1. Complete the missing molecular functions: For proteins currently annotated with GO:0003674, either:
  2. Determine specific molecular functions from literature

  3. Note that these are likely scaffold proteins that may require specific molecular function terms

  4. Add missing evidence: Provide evidence for all causal associations.

  5. Review evidence quality: Consider strengthening evidence codes where possible (e.g., from inference to direct experimental evidence).

  6. Ensure pathway completeness: Consider if any known regulators or components of the SIN pathway are missing from the model.

  7. Check additional linkages: Consider whether the SIN pathway should be connected to other pathways, such as cell cycle regulation or actomyosin ring assembly.

Summary

Overall, this is a well-structured GO-CAM model that accurately represents the septation initiation signaling pathway in S. pombe. It contains appropriate molecular functions, biological processes, and cellular components, and most causal associations are well supported by evidence.

The main recommendations are to complete the missing molecular functions, add evidence for all causal associations, and ensure the model represents the complete current understanding of the SIN pathway.

Model ID: gomodel:66187e4700002284