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Based on my review of the GO-CAM model, related publications, and the knowledge about best practices, I'll now provide a comprehensive review of this GO-CAM model.

Review of GO-CAM Model: gomodel:5fb9cc0600000156

Summary

This GO-CAM model represents the relationships between circadian rhythm and hematopoiesis in zebrafish, mediated by proteins such as Ezh2, Per1b, Cry1a, and the CLOCK-BMAL transcription complex. The model is based primarily on the research published in PMID:29447387, which demonstrated that Ezh2 promotes clock function and hematopoiesis independent of its histone methyltransferase activity in zebrafish.

Model Title and Focus

  • Title: "circadian rhythm and hematopoiesis via ezh2, per1b, cry1a etc. (D. rerio)"
  • Taxon: Danio rerio (zebrafish)
  • Status: Production

Strengths of the Model

  1. Biological accuracy: The model accurately captures key findings from the primary literature (PMID:29447387), showing how Ezh2 functions in both circadian regulation and hematopoiesis.

  2. Complex representation: The CLOCK-BMAL transcription complex (GO:1990513) is appropriately represented with its member proteins (clocka and bmal1b), following GO-CAM best practices.

  3. Appropriate use of causal relationships: The model uses appropriate causal relationships such as "directly positively regulates" (RO:0002629) and "directly negatively regulates" (RO:0002630) to show the regulatory interactions between proteins.

  4. Cellular context representation: The model includes biological processes like "circadian regulation of gene expression" (GO:0032922) and "hemopoiesis" (GO:0030097), providing important cellular context.

  5. Evidence quality: The model uses appropriate evidence codes, with experimental evidence from the primary publication.

Issues and Recommendations

1. Activity Flow Inconsistencies

Some activities in the model appear disconnected or have unclear relationships. For example: - Activity node 5fb9cc0600000185 (Ezh2 with transcription coregulator activity) doesn't have any downstream causal associations. - Several activities (e.g., 5fb9cc0600000205, Per1b with molecular function) are shown as endpoints without further connections, which doesn't fully represent their role in the pathway.

Recommendation: Review the activities that appear as endpoints and connect them to downstream processes where appropriate, based on the literature.

2. Redundant Annotations

There are multiple instances of the same protein being annotated with similar functions in slightly different contexts: - Ezh2 is represented multiple times with transcription coactivator activity (GO:0003713) in different nodes - Similar redundancy exists for Cry1a and the CLOCK-BMAL complex

Recommendation: Consider consolidating redundant activities to simplify the model and improve readability while maintaining biological accuracy.

3. Evidence Documentation

While the model cites appropriate evidence, some activity nodes lack specific evidence codes, showing only empty evidence arrays.

Recommendation: Add appropriate evidence codes and references for all activity nodes to increase the model's credibility and traceability.

4. Molecular Function Annotations

Some nodes use the generic "molecular_function" term (GO:0003674) where more specific functions could be used: - Node 5fb9cc0600000205 (Per1b) is annotated with GO:0003674 - Node 60747c4200000570 (lck) is also annotated with GO:0003674

Recommendation: Replace generic GO:0003674 annotations with more specific molecular functions based on the literature. For Per1b, a more appropriate term might be related to its role in circadian regulation.

5. Part-of Relationships

Not all activities have appropriate "part_of" relationships to biological processes, which reduces the contextual information available in the model.

Recommendation: Ensure each activity is associated with the appropriate biological process through "part_of" relationships.

Specific Literature Consistency Check

The primary findings from PMID:29447387 that are well-captured in the model include:

  1. Ezh2 regulation by the circadian clock via E-box and RORE motifs
  2. Ezh2's role in positively regulating key circadian clock genes
  3. Involvement of Ezh2 in hematopoiesis through regulating genes like cmyb and lck
  4. The interaction between Ezh2 and the Clock-Bmal1 complex

These aspects are reasonably represented in the model's structure, though some connections could be strengthened as noted above.

Overall Assessment

This is a good quality GO-CAM model that captures important relationships between circadian rhythm and hematopoiesis in zebrafish. The model would benefit from some refinements to improve its clarity, comprehensiveness, and evidential support. The connections between activities could be optimized to better represent the pathway flow as described in the literature.

The model successfully integrates findings from the primary research paper and represents complex biological relationships in a structured manner that aligns with GO-CAM best practices, particularly in the representation of protein complexes.