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6446bfcb00001774 Autophagosome assembly Human

Based on my review of the GO-CAM model and the relevant guidelines, here's my assessment of the "Autophagosome assembly (Human)" model (gomodel:6446bfcb00001774):

GO-CAM Review: Autophagosome assembly (Human) - gomodel:6446bfcb00001774

Overview

This model represents the process of autophagosome assembly in humans (NCBITaxon:9606), which is a key process in autophagy. The model includes multiple molecular activities involved in phagophore initiation, elongation, and autophagosome formation.

Strengths

  1. Comprehensive pathway representation: The model provides a detailed representation of autophagosome assembly with 30+ activities involving key proteins like ULK1, ATG proteins, PI3K complex components, and LC3/GABARAP family proteins.

  2. Appropriate subcellular localization: Activities are correctly localized to appropriate cellular components (phagophore assembly site, autophagosome membrane, etc.).

  3. Well-evidenced assertions: All activities have evidence codes and literature references supporting the annotations.

  4. Causal connectivity: The model shows appropriate causal connections between activities (using RO:0002629 for direct positive regulation and RO:0002413 for providing input).

Issues and Recommendations

  1. Evidence code inconsistency:

  2. In activity ID gomodel:6446bfcb00001774/645d887900001734 (AMBRA1), the cellular location evidence references "PMID:cytoplasm" instead of a proper PMID. This should be corrected with a valid PMID reference.

  3. Redundant causal connections:

  4. Several activities have duplicate causal associations with the same predicate to the same downstream activity. For example:
    • In activity ID gomodel:6446bfcb00001774/645d887900001770 (BECN1), there are two identical causal associations to the same downstream activity.
    • In activity ID gomodel:6446bfcb00001774/646ff70100000384 (ATG4C), there are duplicate causal associations to activity 646ff70100000276.

  5. These redundancies should be removed to maintain model clarity.

  6. Missing evidence in causal associations:

  7. Several causal associations have empty evidence lists. For example:
    • Activity ID gomodel:6446bfcb00001774/645d887900001924 has a causal association with no evidence.
    • Activity ID gomodel:6446bfcb00001774/645d887900001755 has a causal association with empty evidence.

  8. All causal associations should have supporting evidence.

  9. Molecular adaptor annotation improvement:

  10. According to the molecular adaptor annotation guidelines, adaptors should have inputs specified through the "has_input" relation. However:

    • Activity ID gomodel:6446bfcb00001774/645d887900001770 (BECN1) with adaptor activity doesn't specify all its inputs.
    • Activity ID gomodel:6446bfcb00001774/646ff70100002442 (WIPI1) with adaptor activity correctly specifies CHEBI:58088 as input but may be missing other relevant inputs.

  11. Regulatory relationship representation:

  12. The inhibitory activity of MTOR (P42345) on AMBRA1 is correctly represented with RO:0002630 (directly negatively regulates), but there's a duplicate causal association that should be removed.

  13. Complex representation:

  14. For the PI3K complex involved in autophagosome assembly, the model correctly represents individual activities of proteins like BECN1 and PIK3C3 rather than using a complex identifier, which is appropriate since the individual activities are known.

Recommendations for Improvement

  1. Fix the evidence code "PMID:cytoplasm" in activity ID gomodel:6446bfcb00001774/645d887900001734.

  2. Remove redundant causal associations to improve model clarity.

  3. Add proper evidence to all causal associations that currently have empty evidence fields.

  4. For molecular adaptors (BECN1, WIPI1), ensure all relevant molecules they bring together are specified as inputs.

  5. Consider adding more information about the relationship between phospholipid binding activities and membrane recruitment in phagophore elongation.

Conclusion

This GO-CAM model provides a comprehensive representation of autophagosome assembly in humans with good biological accuracy and evidence support. With the minor improvements suggested above, it will be an excellent resource for understanding autophagy regulation and autophagosome formation.

The model effectively captures the step-wise process of autophagosome assembly, from ULK1 kinase activity initiating the process to the conjugation of LC3/GABARAP family proteins to the autophagosome membrane, which is consistent with current knowledge of autophagy.