From 20be00920aa68c705d5fa194291c2fece552683a Mon Sep 17 00:00:00 2001 From: j Date: Mon, 29 Jun 2026 21:32:39 +0700 Subject: [PATCH 1/2] =?UTF-8?q?fix:=20correct=20SEED-020=20novelty=20?= =?UTF-8?q?=E2=80=94=20VAR=5F004/VAR=5F002=20are=20CLOSE=5FRELATIVE=20with?= =?UTF-8?q?=20patent=20risk?= MIME-Version: 1.0 Content-Type: text/plain; charset=UTF-8 Content-Transfer-Encoding: 8bit Full BLOSUM62 audit against 27,234-sequence DB (APD6+DRAMP general+patent+UniProt) reveals the preliminary broad novelty check (72-AMP curated DB, no patent sequences) was misleading: - SEED-020_VAR_004 (RLRIRVLKRLLK): 75% identity to DRAMP05502 (patent) - SEED-020_VAR_002 (KVRIRVLKRLLK): 67% identity to DRAMP05504 (patent) Both reclassified CLOSE_RELATIVE / POSSIBLE_PATENT_RISK. Docs updated: - WET_LAB_HANDOFF.md: table corrected, IP NOTE expanded to cover all three SEED-019/020 candidates, Novelty paragraph rewritten; SEED-020_VAR_008 (RVRIKVLKRLLK; CLEAR, no patent DB hit) added as the safe fallback - EXPERT_REVIEW_PACK.md: family table corrected; wave 0.5b addendum rewritten with explicit ⚠ correction block naming DRAMP05502/05504 alignments Local outputs/wave1_final_panel.csv updated (gitignored): novelty_class corrected from NOVEL → CLOSE_RELATIVE for VAR_004 and VAR_002. All 1372 tests pass. --- docs/EXPERT_REVIEW_PACK.md | 36 ++++++++++++++++---------- docs/WET_LAB_HANDOFF.md | 53 ++++++++++++++++++++++++++------------ 2 files changed, 59 insertions(+), 30 deletions(-) diff --git a/docs/EXPERT_REVIEW_PACK.md b/docs/EXPERT_REVIEW_PACK.md index bbde245f..323f85e2 100644 --- a/docs/EXPERT_REVIEW_PACK.md +++ b/docs/EXPERT_REVIEW_PACK.md @@ -174,19 +174,29 @@ not a claim that they are inactive. | SEED-007 (bombolitin) | 4 | Short amphipathic helix | Genuine (✓ NOVEL) | Low (11 AA; good) | ~70–82% | Novel short helix | | SEED-008 (Trp-rich) | 4 | Indole ring stacking; not helical | Genuine (✓ NOVEL) | Moderate (13 AA model edge) | ~70–82% | Novel mechanism; high disagreement | | SEED-009 (Pro-rich) | 4 | Ribosome exit + DnaK | Genuine (✓ NOVEL) | **Best** (Pro-X bonds resist protease) | ~60–75% | Novel; run RPMI parallel | -| SEED-019/020 (Arg-Ile/Val/Leu) | 3 | Cationic amphipathic helix | ✓ NOVEL (SEED-020 pair); CLOSE_RELATIVE + ⚠ patent risk (SEED-019_VAR_004) | Short (12 AA model edge) | **~75–85%** (SEED-020 pair); patent clearance needed for SEED-019_VAR_004 | Best ext.-predictor confirmed leads; IP check before SEED-019 synthesis | - -> **Wave 0.5b addendum (2026-06-29):** External predictor screening (CAMPR4 × 4 votes, -> AMPScanner v2, Macrel, AMPActiPred, HemoFinder, AntiCP2) of 23 new SEED-020/021/023/024 -> candidates confirmed SEED-020_VAR_004 (RLRIRVLKRLLK) and SEED-020_VAR_002 (KVRIRVLKRLLK) -> as the best safety-activity tradeoff in the batch: HemoFinder LOW, AMPScanner > 0.99, -> Non-AntiCP. Both confirmed NOVEL by broad novelty check (72-AMP curated DB; < 50% max -> similarity; no patent DB matches). Both added to `outputs/wave1_final_panel.csv` as -> BALANCED_LEAD candidates (source: WAVE0_5B). SEED-019_VAR_004 (already in panel) carries -> a POSSIBLE_PATENT_RISK flag (66.7% to DRAMP05502 in full 27,234-sequence audit) — require -> IP clearance before synthesis. SEED-022 was excluded at pre-screen (no viable candidates -> after safety scoring; poor AntiCP / HemoFinder profile across all variants). Full synthesis -> notes: `docs/WET_LAB_HANDOFF.md §SEED-019/SEED-020`. +| SEED-019/020 (Arg-Ile/Val/Leu) | 3 | Cationic amphipathic helix | CLOSE_RELATIVE + ⚠ patent risk for all 3 (DRAMP05502/05504); CLEAR alternative: VAR_008 | Short (12 AA model edge) | **~75–85%** (activity unchanged); IP clearance required before any synthesis | Best ext.-predictor confirmed leads; VAR_008 is the publication-safe option | + +> **Wave 0.5b addendum (2026-06-29; novelty corrected 2026-06-29):** External predictor +> screening (CAMPR4 × 4 votes, AMPScanner v2, Macrel, AMPActiPred, HemoFinder, AntiCP2) of +> 23 new SEED-020/021/023/024 candidates confirmed SEED-020_VAR_004 (RLRIRVLKRLLK) and +> SEED-020_VAR_002 (KVRIRVLKRLLK) as the best safety-activity tradeoff in the batch: +> HemoFinder LOW, AMPScanner > 0.99, Non-AntiCP. Both added to `outputs/wave1_final_panel.csv` +> as BALANCED_LEAD candidates (source: WAVE0_5B). +> +> **⚠ Novelty correction:** The preliminary broad novelty check (72-AMP curated DB, no patent +> sequences) returned NOVEL for SEED-020_VAR_004 and SEED-020_VAR_002. The full 27,234-sequence +> BLOSUM62 audit (APD6 + DRAMP general + DRAMP patent + UniProt) reclassifies both as +> **CLOSE_RELATIVE with POSSIBLE_PATENT_RISK**: +> - SEED-020_VAR_004: **75% identity to DRAMP05502** (patent; RLLKQWPIGRLLKRLLKRLLK — +> C-terminal repeat RLLK aligns 9/12 residues) +> - SEED-020_VAR_002: **67% identity to DRAMP05504** (patent; RVLKQWPIGRVLKRVLKRVLK) +> - SEED-019_VAR_004: 66.7% to DRAMP05502 (patent; already flagged) +> +> All three require IP clearance before synthesis or publication. **Publication-safe +> alternative: SEED-020_VAR_008 (RVRIKVLKRLLK)** — 67% to DRAMP31150 (general public +> database, no patent hit; classified CLEAR). SEED-022 was excluded at pre-screen (no viable +> candidates after safety scoring; poor AntiCP / HemoFinder profile across all variants). +> Full synthesis and IP notes: `docs/WET_LAB_HANDOFF.md §SEED-019/SEED-020`. **SEED-007 reviewer note:** Bombolitin-II (*Megabombus pennsylvanicus* venom) is the **largest selected family** (26 variants, 4 pilot slots). All 4 pilot candidates are NOVEL diff --git a/docs/WET_LAB_HANDOFF.md b/docs/WET_LAB_HANDOFF.md index 9c52a381..3a6366f4 100644 --- a/docs/WET_LAB_HANDOFF.md +++ b/docs/WET_LAB_HANDOFF.md @@ -450,27 +450,46 @@ confirmed by external predictor screening (wave 0.5b; 2026-06-29). **Best candidates added to final panel (wave 0.5b, external predictor confirmed):** -| Candidate | Sequence | AMPScanner | HemoFinder | AntiCP | Broad novelty (72-AMP DB) | Full-DB novelty | +| Candidate | Sequence | AMPScanner | HemoFinder | AntiCP | Broad novelty (72-AMP DB only) | Full-DB novelty (27,234-seq BLOSUM62) | |-----------|----------|:----------:|:----------:|:------:|:-------------:|:---:| -| SEED-020_VAR_004 | RLRIRVLKRLLK | 0.9928 (AMP) | LOW | Non-AntiCP 0.29 | NOVEL (41.7% max) | NOVEL | -| SEED-020_VAR_002 | KVRIRVLKRLLK | 0.9960 (AMP) | LOW | Non-AntiCP 0.32 | NOVEL (37.5% max) | NOVEL | -| SEED-019_VAR_004 | RVRIRLVKRLLK | panel anchor | LOW | Non-AntiCP | 38.1% max vs non-patent AMPs | **CLOSE_RELATIVE ⚠ patent risk** | - -> **IP NOTE — SEED-019_VAR_004:** Full 27,234-sequence novelty audit v2 (APD6, DRAMP general, -> DRAMP patent, UniProt) classifies SEED-019_VAR_004 as **CLOSE_RELATIVE (66.7% identity to -> DRAMP patent sequence DRAMP05502)**. **IP clearance is required before ordering synthesis -> or publishing results for SEED-019_VAR_004.** The SEED-020 pair (VAR_004 and VAR_002) were -> not flagged in the patent database and carry no identified IP risk. +| SEED-020_VAR_004 | RLRIRVLKRLLK | 0.9928 (AMP) | LOW | Non-AntiCP 0.29 | NOVEL (41.7% max) | ⚠ CLOSE_RELATIVE 75% to DRAMP05502 (patent) | +| SEED-020_VAR_002 | KVRIRVLKRLLK | 0.9960 (AMP) | LOW | Non-AntiCP 0.32 | NOVEL (37.5% max) | ⚠ CLOSE_RELATIVE 67% to DRAMP05504 (patent) | +| SEED-020_VAR_008 | RVRIKVLKRLLK | ext. pred. confirmed | LOW | — | — | CLOSE_RELATIVE 67% to DRAMP31150 (**CLEAR** — public DB, no patent) | +| SEED-019_VAR_004 | RVRIRLVKRLLK | panel anchor | LOW | Non-AntiCP | 38.1% max vs non-patent AMPs | **CLOSE_RELATIVE ⚠ patent risk** (66.7% to DRAMP05502) | + +> **IP NOTE — SEED-020_VAR_004, SEED-020_VAR_002, and SEED-019_VAR_004:** +> Full 27,234-sequence novelty audit v2 (APD6, DRAMP general, DRAMP patent, UniProt; BLOSUM62 +> local alignment) reveals patent proximity for all three candidates: +> - **SEED-020_VAR_004** (RLRIRVLKRLLK): 75% identity to DRAMP patent sequence **DRAMP05502** +> (RLLKQWPIGRLLKRLLKRLLK; C-terminal RLLK-repeat region aligns 9/12 residues) +> - **SEED-020_VAR_002** (KVRIRVLKRLLK): 67% identity to DRAMP patent sequence **DRAMP05504** +> (RVLKQWPIGRVLKRVLKRVLK; analogous C-terminal alignment) +> - **SEED-019_VAR_004** (RVRIRLVKRLLK): 66.7% identity to DRAMP05502 (patent) +> +> All three are classified **POSSIBLE_PATENT_RISK**. **IP clearance is required before +> ordering synthesis or publishing results for any of these three sequences.** +> +> The preliminary broad novelty check used a 72-sequence curated database that does NOT include +> patent sequences; that check returned NOVEL for SEED-020_VAR_004 and SEED-020_VAR_002 — +> that result was misleading and is superseded by the full-DB BLOSUM62 audit above. +> +> **Safest wave 0.5b alternative — SEED-020_VAR_008 (RVRIKVLKRLLK):** 67% to DRAMP31150 +> (general/public database — no patent hit); classified **CLEAR**. If IP clearance for +> VAR_004/VAR_002 cannot be confirmed before the synthesis deadline, use VAR_008 as the +> primary SEED-020 representative. SEED-020_VAR_004 is the **best safety-activity tradeoff in the entire wave 0.5b batch** by combined external predictor consensus. SEED-020_VAR_002 has the highest AMPScanner score (0.9960) -of any candidate in the batch. - -**Novelty:** SEED-020_VAR_004 and SEED-020_VAR_002 confirmed NOVEL by broad novelty check -(72-AMP curated reference database; < 50% similarity). Closest matches are in the REF-RLK-001 -(cationic helix) and REF-LL37-003 (LL-37 fragment) classes — confirmed activity in either -would be publishable. SEED-019_VAR_004 carries a patent proximity flag (see IP NOTE above); -publishability claims for SEED-019_VAR_004 require IP clearance. +of any candidate in the batch. Both require IP clearance before synthesis (see IP NOTE above). + +**Novelty:** The preliminary broad novelty check (72-AMP curated DB; <50% similarity) showed +NOVEL for SEED-020_VAR_004 and VAR_002, but this database does not include patent sequences. +The full BLOSUM62 audit (27,234 sequences including DRAMP patent DB) classifies VAR_004 and +VAR_002 as **CLOSE_RELATIVE with POSSIBLE_PATENT_RISK** (75% to DRAMP05502 and 67% to +DRAMP05504 respectively). Activity confirmed at wet-lab would require patent search and IP +clearance before publication. SEED-020_VAR_008 (RVRIKVLKRLLK; CLEAR, no patent DB match) +is the publication-safe fallback within this scaffold class. SEED-019_VAR_004 also carries +a patent proximity flag (see IP NOTE above). **Mechanism:** Cationic amphipathic helix — alternating hydrophobic (Leu/Val/Ile) and cationic (Arg/Lys) faces interact with anionic bacterial membranes, causing rapid membrane depolarization. From 2c461563cf47d36a1cee2e7a85f5e9fbb7fa7790 Mon Sep 17 00:00:00 2001 From: j Date: Mon, 29 Jun 2026 21:37:45 +0700 Subject: [PATCH 2/2] fix: address code-review MEDIUM/LOW issues on novelty correction docs MIME-Version: 1.0 Content-Type: text/plain; charset=UTF-8 Content-Transfer-Encoding: 8bit - EXPERT_REVIEW_PACK.md table: expand DRAMP shorthand to "VAR_004/VAR_019→DRAMP05502; VAR_002→DRAMP05504" to eliminate ambiguity about which accession covers which candidate - WET_LAB_HANDOFF.md table: mark VAR_008 row as "(fallback — see IP NOTE)" to prevent technicians from treating it as a current panel member - WET_LAB_HANDOFF.md Novelty prose: tighten "no patent DB match" to "public DRAMP entry, no patent sub-database hit" matching EXPERT_REVIEW_PACK phrasing for precision All 1372 tests pass. --- docs/EXPERT_REVIEW_PACK.md | 2 +- docs/WET_LAB_HANDOFF.md | 6 +++--- 2 files changed, 4 insertions(+), 4 deletions(-) diff --git a/docs/EXPERT_REVIEW_PACK.md b/docs/EXPERT_REVIEW_PACK.md index 323f85e2..d28f0e24 100644 --- a/docs/EXPERT_REVIEW_PACK.md +++ b/docs/EXPERT_REVIEW_PACK.md @@ -174,7 +174,7 @@ not a claim that they are inactive. | SEED-007 (bombolitin) | 4 | Short amphipathic helix | Genuine (✓ NOVEL) | Low (11 AA; good) | ~70–82% | Novel short helix | | SEED-008 (Trp-rich) | 4 | Indole ring stacking; not helical | Genuine (✓ NOVEL) | Moderate (13 AA model edge) | ~70–82% | Novel mechanism; high disagreement | | SEED-009 (Pro-rich) | 4 | Ribosome exit + DnaK | Genuine (✓ NOVEL) | **Best** (Pro-X bonds resist protease) | ~60–75% | Novel; run RPMI parallel | -| SEED-019/020 (Arg-Ile/Val/Leu) | 3 | Cationic amphipathic helix | CLOSE_RELATIVE + ⚠ patent risk for all 3 (DRAMP05502/05504); CLEAR alternative: VAR_008 | Short (12 AA model edge) | **~75–85%** (activity unchanged); IP clearance required before any synthesis | Best ext.-predictor confirmed leads; VAR_008 is the publication-safe option | +| SEED-019/020 (Arg-Ile/Val/Leu) | 3 | Cationic amphipathic helix | CLOSE_RELATIVE + ⚠ patent risk for all 3 (VAR_004/VAR_019→DRAMP05502; VAR_002→DRAMP05504); CLEAR alternative: VAR_008 | Short (12 AA model edge) | **~75–85%** (activity unchanged); IP clearance required before any synthesis | Best ext.-predictor confirmed leads; VAR_008 is the publication-safe option | > **Wave 0.5b addendum (2026-06-29; novelty corrected 2026-06-29):** External predictor > screening (CAMPR4 × 4 votes, AMPScanner v2, Macrel, AMPActiPred, HemoFinder, AntiCP2) of diff --git a/docs/WET_LAB_HANDOFF.md b/docs/WET_LAB_HANDOFF.md index 3a6366f4..f0c3e67a 100644 --- a/docs/WET_LAB_HANDOFF.md +++ b/docs/WET_LAB_HANDOFF.md @@ -454,7 +454,7 @@ confirmed by external predictor screening (wave 0.5b; 2026-06-29). |-----------|----------|:----------:|:----------:|:------:|:-------------:|:---:| | SEED-020_VAR_004 | RLRIRVLKRLLK | 0.9928 (AMP) | LOW | Non-AntiCP 0.29 | NOVEL (41.7% max) | ⚠ CLOSE_RELATIVE 75% to DRAMP05502 (patent) | | SEED-020_VAR_002 | KVRIRVLKRLLK | 0.9960 (AMP) | LOW | Non-AntiCP 0.32 | NOVEL (37.5% max) | ⚠ CLOSE_RELATIVE 67% to DRAMP05504 (patent) | -| SEED-020_VAR_008 | RVRIKVLKRLLK | ext. pred. confirmed | LOW | — | — | CLOSE_RELATIVE 67% to DRAMP31150 (**CLEAR** — public DB, no patent) | +| SEED-020_VAR_008 *(fallback — see IP NOTE)* | RVRIKVLKRLLK | ext. pred. confirmed | LOW | — | — | CLOSE_RELATIVE 67% to DRAMP31150 (**CLEAR** — public DRAMP entry, no patent sub-database hit) | | SEED-019_VAR_004 | RVRIRLVKRLLK | panel anchor | LOW | Non-AntiCP | 38.1% max vs non-patent AMPs | **CLOSE_RELATIVE ⚠ patent risk** (66.7% to DRAMP05502) | > **IP NOTE — SEED-020_VAR_004, SEED-020_VAR_002, and SEED-019_VAR_004:** @@ -487,8 +487,8 @@ NOVEL for SEED-020_VAR_004 and VAR_002, but this database does not include paten The full BLOSUM62 audit (27,234 sequences including DRAMP patent DB) classifies VAR_004 and VAR_002 as **CLOSE_RELATIVE with POSSIBLE_PATENT_RISK** (75% to DRAMP05502 and 67% to DRAMP05504 respectively). Activity confirmed at wet-lab would require patent search and IP -clearance before publication. SEED-020_VAR_008 (RVRIKVLKRLLK; CLEAR, no patent DB match) -is the publication-safe fallback within this scaffold class. SEED-019_VAR_004 also carries +clearance before publication. SEED-020_VAR_008 (RVRIKVLKRLLK; CLEAR — public DRAMP entry, +no patent sub-database hit) is the publication-safe fallback within this scaffold class. SEED-019_VAR_004 also carries a patent proximity flag (see IP NOTE above). **Mechanism:** Cationic amphipathic helix — alternating hydrophobic (Leu/Val/Ile) and cationic