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2 changes: 1 addition & 1 deletion .github/workflows/main.yaml
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Expand Up @@ -19,7 +19,7 @@ jobs:
runs-on: ubuntu-latest
strategy:
matrix:
python-version: ["3.10", "3.13"]
python-version: ["3.12"]
fail-fast: false

steps:
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31 changes: 31 additions & 0 deletions README.md
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Expand Up @@ -100,6 +100,37 @@ The repository includes example gene reviews for:

Browse the `genes/` directory to see complete examples.

## Case Studies

### PedH (Pseudomonas putida KT2440) - Lanthanide-Dependent Alcohol Dehydrogenase

The review of **pedH** revealed several important curation insights:

#### Key Discoveries

1. **Lanthanide vs Calcium Dependency**: PedH was incorrectly annotated with "calcium ion binding" (GO:0005509) when it actually requires lanthanide ions (La³⁺, Ce³⁺, Pr³⁺, Nd³⁺, Sm³⁺) for activity. This highlights the importance of reviewing automated annotations based on sequence similarity.

2. **Cellular Localization Precision**: Bioinformatics analysis confirmed PedH is a **soluble periplasmic enzyme**, not membrane-associated:
- Signal peptide (aa 1-25) directs export, then is cleaved
- No transmembrane regions in mature protein
- Functions throughout periplasmic space, not just at membrane boundaries
- Led to choosing GO:0042597 (periplasmic space) over GO:0030288 (outer membrane-bounded periplasmic space)

3. **Dual Functional Roles**: PedH serves both as:
- **Metabolic enzyme**: Oxidizes alcohols in 2-phenylethanol degradation pathway
- **Regulatory sensor**: Part of lanthanide-sensing system controlling gene expression via PedS2/PedR2 two-component system

4. **Missing GO Terms Identified**: The review revealed gaps in GO:
- No term for "lanthanide ion binding" (distinct from transition metal binding)
- No term for "lanthanide-dependent alcohol dehydrogenase activity"

#### Lessons for Curation

- **Verify metal cofactors carefully** - Don't assume calcium when other metals are possible
- **Consider protein mobility** - Soluble vs membrane-associated matters for localization terms
- **Look for regulatory functions** - Enzymes may have sensory/regulatory roles beyond catalysis
- **Use bioinformatics to validate** - Signal peptide and TM predictions can clarify localization

## Anti-Hallucination Validation

The AI Gene Review system implements a robust **anti-hallucination validation mechanism** using **ID/label tuple checksums** to prevent AI systems from fabricating or misusing ontological terms.
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12,360 changes: 11,236 additions & 1,124 deletions app/data.js

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