[cschanhniem]

Summary

Pre-wet-lab polish sprint — three improvements that increase scientific rigor and wet-lab success probability:

1. AUPRC benchmark metric

• Added _auprc() to benchmark/retrospective.py (trapezoidal PR-curve integration)
• run_retrospective_benchmark() now returns auprc, auprc_random_baseline, auprc_above_random
• AUPRC is preferable to AUROC for class-imbalanced screening datasets (emphasises precision at the operating point used for selection)
• Random baseline = dataset prevalence; values above baseline indicate positive signal
• 10 new tests covering perfect/worst/random/edge cases + full integration test

2. Two new mechanistically distinct seeds

• SEED-009: Bac2A (RRLPRPPYLPRP, bovine proline-rich cathelicidin)
  • Intracellular DnaK-targeting mechanism — genuinely distinct from all 8 prior membrane-disruption seeds
  • Gram-negative selective; naturally proline-rich (synthesis penalty flagged appropriately)
• SEED-010: KR-12 (KRIVQRIKDFLR, shortest active fragment of human LL-37 cathelicidin)
  • Human origin → clinical relevance context; good selectivity profile (MRSA + E. coli data)
• Effect on calibrated probability: effective independent scaffold families 8 → 10; breaking-news P(≥1) improves from 12–22% to 15–26% (DISCOVERY_PREDICTION External Calibration section updated)

3. Assay pre-registration

• docs/ASSAY_PREREGISTRATION.md: full pre-registration template
  • EUCAST ISO 20776-1 broth microdilution protocol (4 target organisms with QC strains)
  • HC50 hemolysis assay protocol (0.5% hRBC, 541 nm readout)
  • Pre-registered hit criteria and selectivity index thresholds (TI > 10 = PASS)
  • Statistical plan (biological triplicate, geometric mean MIC)
  • Negative result reporting obligations
  • Decision gate table (P1/P2/P3)
  • Signature block for PI, synthesiser, biosafety officer, lab partner

Test plan

• 1182 tests pass (10 new AUPRC tests)
• Pre-push hook CI passed
• Verify make validate-scoring output includes auprc field
• Have domain expert confirm EUCAST broth microdilution parameters in ASSAY_PREREGISTRATION.md
• Check that SEED-009 and SEED-010 generate valid candidates through make generate

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