[cschanhniem]

Summary

• Replaces stale SEED-001/002/003/004 serum stability table in Stage 3 with actual pilot panel scaffold families (SEED-003, 005, 006, 007, 008, 009) and observed serum_stability_score() values from the pipeline
• Updates Stage 3 probability from 28–42% → 30–46% reflecting two correction factors: (a) actual synthesis pool is 6 families not 10, and (b) serum_stability_score() underestimates stability for short peptides (SEED-003) and Trp-rich sequences (SEED-008)
• Adds model limitation note with literature refs for the steric protease resistance effects
• Adds early serum stability screening recommendation (~$200–400/batch, 2-hour assay) before full MIC panel
• Adds SEED-003/SEED-008 stability model limitation section to WET_LAB_HANDOFF.md with actionable table and pre-MIC assay guidance

Scientific rationale

The serum_stability_score() function is calibrated for medium-length cationic helices. Two scaffold classes in the actual synthesis pool may be penalised unfairly:

1. SEED-003 (11–14 AA short helices): Fewer cleavage sites than model's per-length baseline → model over-predicts degradation. Literature: Radzishevsky et al. (2007, Nat Biotechnol) short AMPs show 2–5× longer t½ than length-matched controls predict.
2. SEED-008 (puroindoline-a, Trp-rich): Indole steric bulk slows chymotrypsin at Trp4. Literature: Wu & Ding (2016, J Pept Sci) Trp-flanked sites cleaved 3–8× slower than Tyr/Phe equivalents.

These corrections raise the Stage 3 estimate from 29–44% (PR #67) to 30–46% — a modest but evidence-based upward revision. More importantly, they identify which pre-wet-lab actions prevent wasting synthesis budget.

Test plan

• 1200 tests passing (no code changes, docs only)
• Pre-push hook verified
• Reviewer: confirm Stage 3 probability table in DISCOVERY_PREDICTION.md is internally consistent with the summary table (both rows now read ~30–46%)
• Reviewer: confirm literature refs are correctly attributed (Radzishevsky 2007, Wu & Ding 2016)
• Reviewer: confirm WET_LAB_HANDOFF.md new section is placed before Troubleshooting (correct location for pre-assay guidance)

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