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60d5209a00000521 torso signaling pathway D mel

Now I'll review the GO-CAM model in detail based on the guidelines I've consulted.

GO-CAM Model Review: gomodel:60d5209a00000521 "torso signaling pathway (D.mel)"

Overview

This GO-CAM model represents the torso signaling pathway in Drosophila melanogaster (fruit fly). The model shows a signaling cascade initiated by ligands, receptor activation, and downstream signaling events leading to transcriptional regulation.

Strengths of the Model

  1. Comprehensive pathway representation: The model captures multiple components of the torso signaling pathway, from extracellular ligands to nuclear transcription factors.

  2. Appropriate predicate usage: The model correctly uses RO:0002629 (directly positively regulates) to connect activities in the cascade.

  3. Cellular location annotations: Most activities have appropriate cellular component annotations (e.g., extracellular space for ligands, plasma membrane for receptors).

  4. Evidence codes and references: Most activities include evidence codes and PMIDs supporting the annotations.

  5. Standard signaling pathway structure: The model follows the canonical structure for RTK signaling pathways from ligand → receptor → adaptor → GEF → small G protein → kinase cascade → nuclear targets.

Issues and Recommendations

  1. Unknown molecular functions: Several activities (enabled by FB:FBgn0003867, FB:FBgn0261016, FB:FBgn0005390, FB:FBgn0004650) have molecular function GO:0003674 ("molecular_function"), indicating unknown functions. This is not ideal for a production model.

  2. Recommendation: If possible, update these with more specific molecular functions based on literature.

  3. Incomplete documentation of ligand-receptor interaction: The model shows several putative ligands (tsl, clos, fs1M3, fs1N) acting on the receptor tor, but the mechanism of activation is unclear.

  4. Recommendation: Based on the signaling receptor guidelines, clarify if these are direct ligands or cofactors for receptor activation.

  5. Multiple redundant causal associations: There are some duplicate causal relations, for example: 

    rl (FB:FBgn0003256) --RO:0002630--> gro (FB:FBgn0001139)
    appears twice with the same evidence.

  6. Recommendation: Remove duplicate causal associations.

  7. Incomplete transcription factor connections: The transcription repressor activity of cic (FB:FBgn0262582) is shown to be regulated by rl (FB:FBgn0003256), but its downstream targets are not specified.

  8. Recommendation: According to the DNA-binding transcription factor guidelines, each transcription factor should indicate its target gene(s) with "has input" relations.

  9. Potential missing complex representation: If any of the activities involve protein complexes, these should be represented according to the complex annotation guidelines.

  10. Recommendation: Review literature to determine if any complexes should be explicitly modeled.

Biological Accuracy

The model correctly represents the Torso RTK signaling pathway in Drosophila, showing the canonical activation sequence: 1. Extracellular ligands (trk and others) → 2. Receptor (tor) → 3. Adaptor proteins (Shc, csw, drk) → 4. GEF (Sos) → 5. Small G protein (Ras85D) → 6. MAPK cascade (Raf → Dsor1 → rl) → 7. Transcriptional regulators (cic, gro)

This is consistent with known RTK signaling mechanisms and specifically the torso pathway in Drosophila development.

Summary

The GO-CAM model effectively represents the torso signaling pathway in Drosophila melanogaster. While generally well-constructed and biologically accurate, the model could be improved by:

  1. Specifying molecular functions for the activities currently annotated with the generic "molecular_function" term
  2. Clarifying the precise mechanism of receptor activation by the putative ligands
  3. Removing duplicate causal relations
  4. Completing the transcription factor target annotations
  5. Explicitly modeling any relevant protein complexes

Overall, this is a good production model that provides useful information about the torso signaling pathway, though with some areas for potential refinement.