Skip to content

Now that I have gathered information about the GO-CAM model and examined the best practices for GO-CAM curation, let me provide a comprehensive review of the GO-CAM model "gomodel:63a86a8600001720".

Review of GO-CAM Model gomodel:63a86a8600001720

Model Overview

Title: "The non-canonical inflammasome mediated by Casp11 upon lipopolysaccharide-binding (Mouse)"
Taxon: NCBITaxon:9606 (Human)
Status: Production
ID: gomodel:63a86a8600001720

Summary of Model Content

This GO-CAM model represents the non-canonical inflammasome pathway activated by caspase-11 (Casp11) binding to lipopolysaccharide (LPS) in a mouse model. The model describes a key innate immune pathway where cytosolic LPS from Gram-negative bacteria is directly recognized by caspase-11, leading to its auto-processing and activation. Activated caspase-11 then cleaves gasdermin D (GSDMD) to release its N-terminal domain (GSDMD-NT), which forms pores in the plasma membrane, resulting in pyroptotic cell death and the release of inflammatory cytokines.

Model Strengths

  1. Well-evidenced activities: Each molecular function in the model is supported by appropriate evidence codes (ECO:0000314 - direct assay evidence) and literature references.

  2. Clear causal flow: The model correctly represents the sequence of events from LPS binding to caspase-11, through caspase-11 activation, GSDMD cleavage, to pore formation and inflammasome assembly.

  3. Cellular locations: Each activity is appropriately annotated with cellular locations (cytosol, plasma membrane, etc.).

  4. Part_of relations: Activities are correctly placed within the broader biological processes they contribute to.

Issues and Recommendations

  1. Taxon inconsistency:
  2. The model title indicates it's a mouse model, but the taxon is listed as NCBITaxon:9606 (human).

  3. Recommendation: Change the taxon to NCBITaxon:10090 (mouse) to match the model content and title.

  4. Potential complex annotation issue:

  5. The model includes NLRP3 inflammasome complex assembly (GO:0044546), but no explicit representation of the complex itself.

  6. Recommendation: Consider using GO complex terms to properly represent the inflammasome complex according to the "How to annotate complexes in GO-CAM" guidelines.

  7. Missing causal link:

  8. There's no explicit causal connection between NLRP3's signaling adaptor activity (GO:0035591) and other downstream events.

  9. Recommendation: Add causal links to show how NLRP3 contributes to the overall inflammasome activation process.

  10. Input relation clarification:

  11. Caspase-11 lipid binding (GO:0008289) has CHEBI:58712 (lipid A(4-)) as input, which is appropriate, but the model could benefit from clearer representation of how LPS sensing leads to caspase-11 auto-processing.

  12. Recommendation: Consider adding more detail about the mechanism of caspase-11 activation upon LPS binding.

  13. Biological completeness:

  14. The model does not include the release of IL-1β and IL-18 as final outcomes, which are important consequences of inflammasome activation.

  15. Recommendation: Add these downstream effects to provide a more complete representation of the pathway.

  16. Human counterpart consideration:

  17. Since the model focuses on mouse proteins but is potentially relevant to human biology, adding a note about human orthologs (caspase-4/5) would be valuable.
  18. Recommendation: Add comments noting the human equivalents of key mouse proteins.

Detailed Pathway Analysis

The model correctly represents the following causally linked events:

  1. Caspase-11 (MGI:MGI:107700) binds lipid A (CHEBI:58712) via lipid binding activity (GO:0008289), which occurs in the cytosol (GO:0005829).

  2. This leads to caspase-11's cysteine-type endopeptidase activity (GO:0004197), which is properly represented as auto-processing based on the referenced literature (PMID:30135078).

  3. Activated caspase-11 then cleaves GSDMD (MGI:MGI:1916396), which is accurately represented by a causal chain of molecular functions.

  4. GSDMD, upon cleavage, exhibits phosphatidylinositol-4,5-bisphosphate binding (GO:0005546) and wide pore channel activity (GO:0022829) at the plasma membrane (GO:0005886).

  5. The model also includes NLRP3's role in inflammasome complex assembly, though this connection could be strengthened.

Conclusion

Overall, this is a well-constructed GO-CAM model that accurately represents the non-canonical inflammasome pathway based on current literature. The model follows many GO-CAM best practices regarding evidence, causal relations, and molecular function representation.

The main improvements needed are: 1. Correcting the taxon inconsistency 2. Strengthening the representation of the inflammasome complex 3. Adding missing causal links for NLRP3's role 4. Expanding the model to include downstream cytokine release

With these adjustments, the model would provide an even more accurate and comprehensive representation of this important innate immune pathway.