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665912ed00001983 subtelomeric heterochromatin formation GO 0031509

Based on my review of the model and relevant documentation, I'll now provide a detailed review of GO-CAM model gomodel:665912ed00001983 on "subtelomeric heterochromatin formation (GO:0031509)".

GO-CAM Model Review: Subtelomeric Heterochromatin Formation in S. pombe

Model Overview

The model gomodel:665912ed00001983 describes the process of subtelomeric heterochromatin formation in fission yeast Schizosaccharomyces pombe (NCBITaxon:4896). The model captures multiple activities involved in this complex process, including RNA processing, histone modification, protein binding, adaptor activities, and regulatory relationships between these components.

Strengths of the Model

  1. Comprehensive coverage: The model effectively captures multiple molecular pathways involved in heterochromatin formation, including both RNAi-dependent and RNAi-independent mechanisms.

  2. Well-evidenced: Most activities and relationships are supported by appropriate experimental evidence with clear literature references.

  3. Appropriate cellular components: The model correctly localizes activities to their cellular compartments (e.g., RITS complex, SHREC complex, CLRC complex).

  4. Clear activity flow: The model generally depicts a logical flow of activities showing how different proteins contribute to heterochromatin formation.

Issues and Recommendations

  1. Duplicate causal associations: Several activities have duplicate causal associations with the same predicate and downstream activity:
  2. Activity gomodel:665912ed00001983/665912ed00002048 (enabled by raf1) has two identical causal associations to activity gomodel:665912ed00001983/665912ed00001995 (enabled by clr4) using RO:0002304
  3. Activity gomodel:665912ed00001983/665912ed00002143 (enabled by arb1) has two identical causal associations to activity gomodel:665912ed00001983/665912ed00002158 (enabled by ago1) using RO:0002630
  4. Activity gomodel:665912ed00001983/665912ed00002109 (enabled by dcr1) has two identical causal associations to activity gomodel:665912ed00001983/665912ed00002158 (enabled by ago1) using RO:0002413
  5. Activity gomodel:665912ed00001983/665912ed00002158 (enabled by ago1) has two causal associations to activity gomodel:665912ed00001983/665912ed00002173 (enabled by rdp1) using RO:0002304

Recommendation: Remove duplicate causal associations, keeping only one instance with the strongest evidence.

  1. Missing molecular function terms: Several activities use "GO:0003674" (molecular_function) rather than specific molecular function terms:
  2. Activities enabled by rss1, cul4, raf1, rik1, clr1, clr2, and rad25

Recommendation: Replace generic molecular function terms with more specific terms based on literature evidence when available.

  1. Feedback loops: The model shows several feedback relationships but should clarify the temporal sequence of events, especially between:
  2. SHREC complex components
  3. RITS complex and RNAi machinery

Recommendation: Consider adding annotations to clarify temporal sequence and the biological context of feedback regulation.

  1. Evidence consistency: Some causal associations have strong experimental evidence while others rely on genetic interaction evidence. For example:
  2. The causal association between lsd1/lsd2 activities and sir2 activity is based on genetic interaction evidence

Recommendation: For associations based on genetic evidence, consider adding notes to clarify that these may represent indirect rather than direct relationships.

  1. Molecular adaptor annotations: The model contains a protein with annotated adaptor activity (stc1, GO:0030674). According to GO-CAM best practices, adaptor proteins should follow the guidelines in the "How to annotate molecular adaptors" document.

Recommendation: Review the annotations of adaptors to ensure they follow current best practices.

Technical Model Quality Issues

  1. PMID format inconsistency: In activity gomodel:665912ed00001983/665912ed00001985, there is a malformatted PMID reference: "PMID: 16246721" (contains a space).

  2. Unclear evidence objects: Some evidence statements use "with_objects" whose relationship to the assertion isn't immediately clear.

Biological Accuracy

The model accurately represents current understanding of subtelomeric heterochromatin formation in S. pombe, including:

  1. The role of the RNAi machinery (dcr1, ago1, rdp1, hrr1) in siRNA-mediated heterochromatin formation
  2. The role of the CLRC complex (cul4, rik1, raf1, raf2) in directing the histone methyltransferase clr4
  3. The role of the SHREC complex (clr1, clr2, clr3, mit1) in histone deacetylation
  4. The binding of heterochromatin proteins (swi6, chp1, chp2) to methylated histones
  5. The demethylase activities of lsd1 and lsd2 in regulating histone methylation

The model successfully captures both RNAi-dependent and independent pathways of heterochromatin formation, reflecting the current state of knowledge.

Summary

This is a high-quality model that effectively represents the complex process of subtelomeric heterochromatin formation in S. pombe. The model integrates multiple pathways and molecular components with appropriate evidence. The main improvements needed are technical (removing duplicated causal associations) and adding more specific molecular function terms for some gene products. Overall, the model provides a comprehensive view of this important biological process, connecting histone modifications, RNA processing, and chromatin binding proteins in a coherent framework.