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Based on my review of the GO-CAM model and relevant information, here's my assessment of gomodel:5fce9b7300002336 (SPModule-TREM1-DAP12):

GO-CAM Review: gomodel:5fce9b7300002336 (SPModule-TREM1-DAP12)

Overview

This model represents the signaling pathway involving TREM1 (Triggering receptor expressed on myeloid cells 1) and its adaptor protein DAP12 (TYROBP). The model shows how TREM1 activation leads to downstream signaling through DAP12, ultimately resulting in SYK kinase activity.

Strengths

  1. Accurate molecular relationships: The model correctly depicts TREM1 as a transmembrane signaling receptor that associates with DAP12, which acts as a molecular adaptor. This is consistent with the literature (PMID:10799849, PMID:9490415).

  2. Appropriate causal associations: The model uses the correct causal association predicate (RO:0002629 - directly positively regulates) to show how TREM1 receptor signaling activates DAP12's adaptor activity, which then activates SYK kinase activity.

  3. Cellular localization: The model correctly annotates the activities with appropriate cellular locations - TREM1 at the cell surface (GO:0009986) and ligands in the extracellular space (GO:0005615).

  4. Multiple ligands: The model appropriately shows multiple ligands (PGLYRP1, HMGB1, HSPA1A) that can activate TREM1, which is supported by evidence in the literature (PMID:25595774, PMID:17568691).

  5. Includes decoy receptor activity: The model includes the important regulatory mechanism of the soluble isoform of TREM1 (TREM1-2) acting as a receptor decoy (GO:0140319) that negatively regulates TREM1 signaling.

Areas for Improvement

  1. Complex representation: According to the GO-CAM guidance on representing complexes, in cases where specific subunits carry known activities, each should be explicitly shown. In this model, both TREM1 and DAP12 have specific known functions (receptor activity and adaptor activity respectively), which is correctly represented. However, there should be a clearer indication that these two proteins form a functional complex together.

  2. Evidence details: While the model includes PMID references for the assertions, it might benefit from more specific evidence statements describing exactly what observations from each paper support the stated relationships.

  3. Additional downstream effects: The model shows signaling only as far as SYK kinase activity, but the literature indicates further downstream effects such as calcium mobilization, ERK1/2 phosphorylation, and activation of PLC-γ (as seen in PMID:10799849). These could be added to make the model more comprehensive.

Technical Review

  1. Molecular functions: All activities are annotated with appropriate GO terms:
  2. TREM1: GO:0004888 (transmembrane signaling receptor activity)
  3. DAP12: GO:0060090 (molecular adaptor activity)
  4. SYK: GO:0016301 (kinase activity)
  5. TREM1-2: GO:0140319 (receptor decoy activity)

  6. Ligands: GO:0048018 (receptor ligand activity)

  7. Causal relationships: The causal relationships use the correct relationship predicates:

  8. Ligands directly positively regulate TREM1 (RO:0002629)
  9. TREM1 directly positively regulates DAP12 (RO:0002629)
  10. DAP12 directly positively regulates SYK (RO:0002629)

  11. TREM1-2 directly negatively regulates TREM1 (RO:0002630)

  12. Cellular context: Appropriate cellular locations are provided:

  13. TREM1 and DAP12 at cell surface (GO:0009986)
  14. Ligands in extracellular space (GO:0005615)

Conclusion

The model gomodel:5fce9b7300002336 accurately represents the TREM1-DAP12 signaling pathway with appropriate molecular functions, causal relationships, and cellular contexts. It follows GO-CAM best practices for representation of activities and their relationships.

The model could be enhanced by: 1. Making the TREM1-DAP12 complex relationship more explicit 2. Adding more downstream signaling events beyond SYK activation 3. Providing more detailed evidence statements

Overall, this is a well-constructed GO-CAM model that effectively captures the essential aspects of TREM1-DAP12 signaling.