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feat(panel): integrate wave 0.5b top picks — SEED-020 external predictor confirmation - #109
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…tor confirmation External predictor screening (CAMPR4, AMPScanner v2, Macrel, AMPActiPred, HemoFinder, AntiCP2) of 23 wave 0.5b candidates confirmed SEED-020_VAR_004 (RLRIRVLKRLLK) and SEED-020_VAR_002 (KVRIRVLKRLLK) as the best safety-activity leads in the batch. Broad novelty check confirms both are NOVEL (< 50% similarity to the 72-AMP curated reference database; max similarity 41.7% vs REF-RLK-001 and 37.5% vs REF-LL37-003). Key external predictor metrics: - SEED-020_VAR_004: AMPScanner 0.9928, HemoFinder LOW, Non-AntiCP 0.29 (cleanest in batch) - SEED-020_VAR_002: AMPScanner 0.9960 (highest in batch), HemoFinder LOW, Non-AntiCP 0.32 Both outperform SEED-019_VAR_004 on the AntiCP off-target safety criterion while maintaining equivalent activity. Both are NOVEL — confirmed activity is publishable. Changes: - docs/WET_LAB_HANDOFF.md: new SEED-019/020 section — scaffold description, synthesis guidance (Nα-Ac REQUIRED for 5 trypsin sites, C-amide recommended, SHORT_PEPTIDE serum note, Macrel hemolysis false-positive warning), assay priority note (SAR triad comparison with SEED-019_VAR_004 within same assay plate) - docs/EXPERT_REVIEW_PACK.md: §5 family table extended with SEED-019/020 row (P(≥1 active) ~78–87%, best ext-predictor confirmed); wave 0.5b addendum block added below table summarising the confirmation rationale - docs/ROADMAP.md: PR tracking entries for PR #104 (SEED-006 Met fix) and this PR wave1_final_panel.csv updated locally (outputs/ is gitignored): SEED-020_VAR_004 and SEED-020_VAR_002 added as BALANCED_LEAD (WAVE0_5B). Tests: 1372 passed.
…5b PR HIGH — SEED-019_VAR_004 classified NOVEL in new docs but is CLOSE_RELATIVE with POSSIBLE_PATENT_RISK in official novelty audit v2 (66.7% to DRAMP05502). Added explicit IP NOTE block in WET_LAB_HANDOFF.md; added patent risk flag to EXPERT_REVIEW_PACK.md §5 row and wave 0.5b addendum; publishability claim scoped to SEED-020 pair only. HIGH — Arg count/charge density errors: "≥4 Arg" doesn't apply to KVRIRVLKRLLK (3 Arg + 3 Lys = 6 cationic); net charge "+4 to +5" incorrect — should be "+5 to +6". Fixed to "3–4 Arg plus 2–3 Lys, 6 total cationic, net charge ~+5 to +6." HIGH — Nα-Ac rationale conflated exopeptidase + endopeptidase protection. Added explicit clarification: Nα-Ac blocks aminopeptidase (exopeptidase) from the free α-amine; trypsin endoproteolysis at 5 K/R sites requires D-amino Wave 2. MEDIUM — Motif descriptor removed (had positional errors: K at pos1 for VAR_002, V/L order mismatch for SEED-019); replaced with prose description of the pattern. MEDIUM — Macrel bias characterization changed from "all cationic helices" to "non-discriminating in this dataset — 60/60 candidates flagged regardless of class" (matches documented evidence in METRICS_CURRENT.md). MEDIUM — P(≥1 active) range adjusted from 78–87% to 75–85% in EXPERT_REVIEW_PACK §5; "best ext. predictor confirmed leads" clarification added to reviewer focus. LOW — Melittin cross-reference removed; now cites docs/METRICS_CURRENT.md. LOW — SEED-022 documented in addendum (excluded at pre-screen, no viable candidates after safety scoring). Tests: 1372 passed.
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Summary
External predictor screening of 23 wave 0.5b candidates (CAMPR4, AMPScanner v2, Macrel, AMPActiPred, HemoFinder, AntiCP2) identified the two best safety-activity leads:
RLRIRVLKRLLK): AMPScanner 0.9928, HemoFinder LOW, Non-AntiCP 0.29 — best safety profile in batchKVRIRVLKRLLK): AMPScanner 0.9960 (highest in batch), HemoFinder LOW, Non-AntiCP 0.32Both confirmed NOVEL by broad novelty check (72-AMP curated database, < 50% max similarity). Both outperform SEED-019_VAR_004 on the AntiCP off-target safety criterion while maintaining equivalent activity scores.
Changes
docs/WET_LAB_HANDOFF.md: New SEED-019/020 section — Arg-Ile/Val/Leu scaffold description, synthesis guidance (Nα-Ac REQUIRED for 5 trypsin sites, C-amide recommended, Macrel hemolysis false-positive warning), SAR triad assay priority notedocs/EXPERT_REVIEW_PACK.md: §5 family table extended with SEED-019/020 row (P(≥1 active) ~78–87%); wave 0.5b addendum block addeddocs/ROADMAP.md: PR tracking entries for PR fix(docs+qc): correct SEED-006 Met synthesis error and close expert-pack gaps #104 and this PRoutputs/wave1_final_panel.csv(local only, gitignored): SEED-020_VAR_004 and SEED-020_VAR_002 added as BALANCED_LEAD candidates from WAVE0_5B sourceTest plan
make test→ 1372 tests pass (verified locally)docs/WET_LAB_HANDOFF.mdSEED-019/020 section present with correct synthesis flags (Nα-Ac REQUIRED, C-amide RECOMMENDED, SHORT_PEPTIDE note)docs/EXPERT_REVIEW_PACK.md§5 table includes SEED-019/020 row🤖 Generated with Claude Code