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After reviewing all the information, I will now provide a comprehensive review of GO-CAM model 613aae0000000040 (cGAS-Sting pathway in Drosophila):

Review of GO-CAM Model: cGAS-Sting pathway (Drosophila)

Model Overview

  • Model ID: gomodel:613aae0000000040
  • Title: cGAS-Sting pathway (Drosophila)
  • Taxon: Drosophila melanogaster (NCBITaxon:7227)
  • Status: Production

Model Content Overview

This model represents the cGAS-STING pathway in Drosophila, focusing on antiviral immunity. It includes:

  1. Two cGAS-like receptors (cGLR1 and cGLR2) that sense RNA and produce cyclic dinucleotides
  2. STING protein that binds these cyclic dinucleotides
  3. Downstream signaling leading to activation of the Rel transcription factor (NF-κB homolog)
  4. All activities are part of the "defense response to virus" (GO:0051607) biological process

Key Activities and Causal Associations

The model includes the following core activities: 1. cGLR2 (FB:FBgn0050424) has two activities: - 2',3'-cyclic GMP-AMP synthase activity (GO:0061501) - 3',2'-cyclic GMP-AMP synthase activity (GO:0140700) - Both provide input to STING protein (RO:0002413)

  1. cGLR1 (FB:FBgn0034047) has two activities:
  2. Double-stranded RNA binding (GO:0003725)
  3. 3',2'-cyclic GMP-AMP synthase activity (GO:0140700)

  4. Both directly positively regulate STING (RO:0002629 and RO:0002413)

  5. STING (FB:FBgn0033453) has two binding activities:

  6. 2',3'-cyclic GMP-AMP binding (GO:0061507)
  7. 3',2'-cyclic GMP-AMP binding (GO:0140704)

  8. Both directly positively regulate Rel (RO:0002629)

  9. Rel (FB:FBgn0014018) has transcription factor activity (GO:0000981)

  10. Part of defense response to virus (GO:0051607)

Evidence Support

The model is well-supported by recent primary literature: - PMID:34261128 (2021) - Two cGAS-like receptors induce antiviral immunity in Drosophila - PMID:34261127 (2021) - Related to cGAS-like receptors and RNA sensing - PMID:33262294 (2020) - Related to STING activation - PMID:19135474 (2009) - Related to Rel transcription factor activity - PMID:30119996 (2018) - Related to antiviral response

Quality Assessment

Strengths

  1. Good representation of the current literature: The model accurately captures the latest findings about the cGAS-STING pathway in Drosophila, where cGAS-like receptors (cGLRs) detect RNA and produce cyclic dinucleotides to activate STING.

  2. Appropriate causal relationships: The model uses appropriate relationship predicates:

  3. "provides input for" (RO:0002413) for substrate-product relationships

  4. "directly positively regulates" (RO:0002629) for regulatory relationships

  5. Consistent biological process annotation: All activities are appropriately annotated as part of the defense response to virus (GO:0051607).

  6. Logical flow: The pathway representation follows a clear sequence from sensor proteins (cGLRs) to effector (Rel transcription factor).

Areas for Improvement

  1. Upstream signal representation: The model could be improved by including the upstream viral RNA that triggers the pathway. The model starts with the cGLR activities but does not explicitly represent what activates these proteins.

  2. Molecular details: While the model shows the cyclic dinucleotide synthase and binding activities, it would be beneficial to include the specific molecules involved (e.g., dsRNA, 2',3'-cGAMP, 3',2'-cGAMP) as chemical entities within the model.

  3. Downstream targets: The model represents Rel transcription factor activity but doesn't include any downstream target genes. Including key antiviral genes regulated by Rel would complete the signaling pathway.

  4. Alternative pathways: The literature suggests that the two cGLRs may have somewhat distinct roles. The model could potentially clarify if there are any pathway-specific differences between cGLR1 and cGLR2 signaling.

Consistency with GO-CAM Guidelines

The model generally follows GO-CAM best practices:

  1. Activity representation: Each activity is appropriately enabled by a specific gene product.

  2. Process context: All activities are correctly placed within a biological process context.

  3. Causal relationships: The model uses appropriate causal relationships between activities.

  4. Evidence: Each assertion is supported by evidence from the literature.

Recommendations for Improvement

  1. Add upstream stimulus: Include viral RNA as a trigger for cGLRs to provide more complete context.

  2. Include molecular participants: Add the cyclic dinucleotides as participants in the model.

  3. Expand downstream effects: Include key antiviral genes regulated by Rel transcription factor.

  4. Consider adding complex representation: If the cGLRs or STING function as part of larger complexes, these could be represented following GO-CAM complex guidelines.

  5. Clarify specific roles: Provide more detail on any distinct roles of cGLR1 versus cGLR2 if indicated by the literature.

Conclusion

This GO-CAM model effectively represents the cGAS-STING pathway in Drosophila as described in recent literature. It captures the core signaling pathway from RNA sensing by cGAS-like receptors through cyclic dinucleotide production, STING activation, and downstream Rel transcription factor activity. While generally well-constructed, the model could be enhanced by including upstream stimuli, molecular participants, and downstream targets to provide a more complete representation of the pathway.