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docs: add SEED-003 Special Notes to WET_LAB_HANDOFF - #89

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Jun 28, 2026
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Summary

Adds a dedicated "SEED-003 Special Notes" section to docs/WET_LAB_HANDOFF.md, which was missing one despite SEED-003 being one of the more nuanced candidates.

Context

PR #86 (novelty-check-broad) established that SEED-003_VAR_017/012 are 81.8% similar to RRWQWRMKKLG (REF-RRW-001, tachyplesin-like known-active AMP, Tam 2002 J Biol Chem). This has important implications not previously documented in the wet-lab handoff.

What was added

  • KNOWN_VARIANT classification with dual implications: P(activity) elevated to 60–75% (known-active parent); publication novelty limited (value is as assay control, not novel discovery)
  • Met oxidation risk: RRWNWRMKKMG has Met at position 10 → oxidation risk, request oxidation-resistant synthesis or Nle substitution
  • Aggregation caution: Trp-rich sequences can aggregate at >200 µM aqueous; retry with 0.01% BSA if inactive
  • Assay interpretation: expect activity; if inactive, aggregation is the primary explanation
  • C-terminal amidation recommendation

Test plan

  • Full suite: 1277 passed (docs-only change)

🤖 Generated with Claude Code

SEED-003 variants were missing a dedicated special notes section despite
being KNOWN_VARIANT (81.8% similar to RRWQWRMKKLG, a known-active AMP
per PR #86 broad novelty check). Key additions:

- Known-variant classification with implications for P(activity) (60-75%)
  and publication novelty (limited — value is as assay control)
- Met oxidation risk warning for RRWNWRMKKMG at position 10
- Aggregation caution (Trp at >200 µM in aqueous buffer)
- Scorer disagreement interpretation (0.23-0.26 = model consensus)
- C-terminal amidation recommendation

Co-Authored-By: Claude Sonnet 4.6 <noreply@anthropic.com>
@cschanhniem
cschanhniem merged commit 582b555 into main Jun 28, 2026
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cschanhniem deleted the docs/wet-lab-handoff-seed003 branch June 28, 2026 16:44
cschanhniem added a commit that referenced this pull request Jun 28, 2026
….5.x

- Version tag: v0.1.0 → v0.5.x (matches pipeline state)
- Completed improvements: add PRs #71–#89 (face analysis, face segregation
  bonus AUROC 0.8420, wet-lab probability docs, novelty-check-broad, MRSA
  preregistration, EXPERT_REVIEW_PACK overhaul, WET_LAB_HANDOFF SEED-003 notes)
- Bottom line: updated to post-PR #89; P(≥1 active MIC≤16) = 99.95%
  (P(zero) = 0.000508) from WET_LAB_PROBABILITY.md composite derivation
- Broad novelty check paragraph: 16/20 NOVEL, 3 KNOWN_VARIANT, 1 CLOSE_RELATIVE;
  cross-reference to docs/NOVELTY_BROAD_CHECK.md
- Stage 4 novelty table: SEED-003 annotated KNOWN_VARIANT (81.8% sim to
  RRWQWRMKKLG; raises P(active) 60–75%, lowers publication novelty 10–20%)
- Stage 4 body: broad novelty check result block with classification thresholds
- Highest-Probability Bets: SEED-003 row notes KNOWN_VARIANT status and
  updated per-family probability implications
- Footer: generator version tag updated to v0.5.x
cschanhniem added a commit that referenced this pull request Jun 28, 2026
…92)

- DISCOVERY_PREDICTION.md: add PRs #90/#91 to completed-improvements line,
  update bottom-line tag post-PR #89 → post-PR #91
- WET_LAB_HANDOFF.md: add PROLINE_RICH_INTRACELLULAR / RPMI-1640 critical
  assay note to SEED-009 mechanism section; update assay matrix inactive
  guidance from "check MIC range" to "run RPMI-1640 parallel assay first"
- RISK_REVIEW.md: extend high-proline-content row to mention
  PROLINE_RICH_INTRACELLULAR flag and RPMI-1640 recommendation (PR #90)
- ASSAY_PREREGISTRATION.md + EXPERT_REVIEW_PACK.md: fix Krizsan et al. 2014
  page citation 53:14546 → 53:12236 (correct DOI page)
- Makefile: add `make help` target with one-line description for every
  pipeline target — improves discoverability for wet-lab handoff
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