Skip to content

665912ed00000459 dolichol linked oligosaccharide biosynthetic process GO 0006488

Let me continue with my review of GO-CAM model 665912ed00000459. This model represents the dolichol-linked oligosaccharide biosynthetic process (GO:0006488) in Schizosaccharomyces pombe (fission yeast).

GO-CAM Review: gomodel:665912ed00000459

Title and Overview

Title: "dolichol-linked oligosaccharide biosynthetic process (GO:0006488)"
Taxon: NCBITaxon:4896 (Schizosaccharomyces pombe)
Status: Production
Comments: "waiting for correct activity for dfg10, need to connect sec9, dfg10, rer2"

Strengths of the Model

  1. Pathway Completeness: The model represents a comprehensive view of the dolichol-linked oligosaccharide biosynthetic pathway, including multiple sequential steps with appropriate enzymes.
  2. Cellular Context: Activities are properly annotated with cellular locations, primarily occurring in the endoplasmic reticulum membrane (GO:0005789).
  3. Causal Connections: Most activities are connected through appropriate causal relationships, forming a coherent pathway flow using RO:0002413 (provides input for).
  4. Evidence Support: Most activities have strong evidence codes, including experimental evidence (ECO:0000315, ECO:0000316) and literature citations.

Issues Identified

  1. Incomplete Connections: The model has a comment indicating that connections between sec9, dfg10, and rer2 need to be completed. This is indeed the case - these components aren't fully integrated into the pathway flow.

  2. Missing Activity: The comment mentions "waiting for correct activity for dfg10" - I see dfg10 (PomBase:SPAC7D4.09c) is annotated with 3-oxo-5-alpha-steroid 4-dehydrogenase activity (GO:0003865), but this may not be the most appropriate activity term based on its role in dolichol biosynthesis.

  3. Duplicate Activities: There are duplicate activities for some proteins, such as:

  4. PomBase:SPBC11B10.01 (alg2) has two activities: GO:0004378 and GO:0102704
  5. PomBase:SPAC1834.05 (alg9) has two activities: GO:0052926 and GO:0052918

  6. PomBase:SPCC330.08 (alg11) appears twice with the same activity GO:0004377

  7. Input/Output Molecules: While some activities have specified input/output molecules, there are inconsistencies:

  8. alg7 (SPBC15D4.04) has CHEBI:16264 (UDP-N-acetyl-alpha-D-glucosamine) listed as input multiple times

  9. Some molecular inputs and outputs are missing for key steps in the pathway

  10. Ambiguous Causal Relationships: Several activities have multiple downstream connections to the same activity, which may create confusion in pathway interpretation.

  11. Uncertain Evidence: Some associations have no evidence codes specified.

Recommendations

  1. Complete Missing Connections:

  2. Connect sec59 (SPCC63.10c), dfg10 (SPAC7D4.09c), and rer2 (SPAC4D7.04c) as mentioned in the comments to show the proper flow of the dolichol biosynthetic process.

  3. Resolve Duplicate Activities:

  4. For molecules with multiple activities, determine whether these are indeed separate functions or redundant annotations, and connect them appropriately in the pathway.

  5. For example, clarify whether alg2 (SPBC11B10.01) performs both GDP-Man:Man1GlcNAc2-PP-Dol alpha-1,3-mannosyltransferase and GDP-Man:Man2GlcNAc2-PP-dolichol alpha-1,6-mannosyltransferase activities sequentially or in different contexts.

  6. Add Missing Input/Output Molecules:

  7. Ensure all activities have their relevant input and output molecules specified to better illustrate the flow of material through the pathway.

  8. Clarify Causal Relationships:

  9. Review cases where multiple causal connections point to the same downstream activity and determine if these represent alternative pathways, redundancy, or modeling errors.

  10. Complete Evidence Documentation:

  11. Add appropriate evidence codes for any associations currently lacking them.

  12. Review Activity for dfg10:

  13. Confirm the appropriate molecular function for dfg10 (SPAC7D4.09c). The current annotation with 3-oxo-5-alpha-steroid 4-dehydrogenase activity may need revision based on its role in dolichol biosynthesis.

Biological Accuracy

The overall biological process represented appears accurate, modeling the dolichol-linked oligosaccharide biosynthetic pathway in fission yeast, which is a conserved pathway involved in N-linked glycosylation. The sequential arrangement of enzymes follows the known steps of this pathway, moving from early glycosylation with N-acetylglucosamine to later additions of mannose and glucose residues.

The model connects many of the key enzymes involved including the ALG family proteins (ALG1, ALG2, ALG3, etc.) that sequentially build the lipid-linked oligosaccharide precursor. The inclusion of dolichol biosynthesis components (dfg10, rer2, sec59) is also biologically appropriate, as dolichol phosphate is a key substrate in this pathway.

Summary

This GO-CAM model provides a good representation of the dolichol-linked oligosaccharide biosynthetic process in S. pombe. While the model has several strengths in terms of pathway coverage and evidence support, there are areas that need improvement, particularly in connecting dolichol biosynthesis to the main pathway, resolving duplicate activities, and ensuring consistent annotation of molecular inputs and outputs. Addressing these issues would improve the model's clarity and biological accuracy.