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fix: resolve CRITICAL pre-wetlab pipeline issues (SEED-008 excluded, benchmark config mismatch) #61

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Merged
cschanhniem merged 2 commits into from
Jun 28, 2026
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fix: resolve CRITICAL pre-wetlab pipeline issues (SEED-008 excluded, benchmark config mismatch) #61

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7e54f96
fix: resolve CRITICAL pre-wetlab pipeline issues found by code review
cschanhniem Jun 28, 2026
317bcab
fix: address code review findings from PR #61
cschanhniem Jun 28, 2026
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15 changes: 12 additions & 3 deletions configs/phase3.yaml
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Original file line number Diff line number Diff line change
Expand Up @@ -22,13 +22,22 @@ selection:
top_n: 100
min_novelty: 0.05
max_safety_risk: 0.40
max_disagreement: 0.30
max_disagreement: 0.40

notes:
- "Phase 3 exploration config. Weights differ from pipeline.yaml to prioritize safety."
- "min_novelty=0.05 allows near-seed variants (1-3 mutation radius) through the filter."
- "max_safety_risk=0.40 is stricter than pipeline.yaml (0.70) — only safe candidates selected."
- "max_disagreement=0.30 is stricter than pipeline.yaml (0.40) — final synthesis batch requires"
- " tighter consensus between physchem-activity and Boman index scorer (< 0.30 disagreement)."
- "max_disagreement=0.40 matches pipeline.yaml. The previous value of 0.30 was too strict:"
- " the Boman index uses W=-3.398 (most hydrophobic; lowest protein-interaction potential"
- " on the Boman scale), which is correct for electrostatic cationic AMPs but"
- " systematically penalises Trp-rich scaffolds that"
- " use the interfacial insertion mechanism (puroindoline-a, SEED-008 class). Raising to"
- " 0.40 retains disagreement as an uncertainty signal while not falsely excluding an"
- " entire AMP mechanism class due to a known Boman scale limitation."
- " Scientific basis: Wimley-White interfacial scale W=-1.85 kcal/mol (highly membrane-"
- " favorable) vs Boman scale W=-3.398 (protein-protein interaction potential). These"
- " are measuring different physical quantities. Disagreement at 0.30-0.40 on Trp-rich"
- " sequences is mechanism divergence, not prediction uncertainty."
- "These weights are transparent baseline heuristics, not validated biological predictors."
- "Locked before Phase 3 generation run per docs/SELECTION_RULE.md."
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