From 9fe66f963c71aee76afc863eef31553f8d7f3b8b Mon Sep 17 00:00:00 2001 From: j Date: Sun, 28 Jun 2026 17:50:25 +0700 Subject: [PATCH] fix: correct stale documentation found in post-PR#61 audit MIME-Version: 1.0 Content-Type: text/plain; charset=UTF-8 Content-Transfer-Encoding: 8bit - WET_LAB_HANDOFF.md: update max_disagreement for phase3.yaml from 0.30→0.40; both configs now use 0.40 since PR #61 reinstated SEED-008 (Trp-rich puroindoline-a) - METHODS.md §4.4 + §9: correct "45-sequence" → "72-sequence" reference set (amp_curated_references.csv has 72 entries; 45 was pre-expansion count) - DISCOVERY_PREDICTION.md: correct "45-sequence" → "72-sequence" in novelty section; fix SEED-005 exemplar from variant KRFFKKIGSALKFA → actual seed KRLFKKIGSALKFL with note that VAR_009 (KRFFKKIGSALKFA) is the best-ranked variant --- docs/DISCOVERY_PREDICTION.md | 4 ++-- docs/METHODS.md | 6 +++--- docs/WET_LAB_HANDOFF.md | 4 ++-- 3 files changed, 7 insertions(+), 7 deletions(-) diff --git a/docs/DISCOVERY_PREDICTION.md b/docs/DISCOVERY_PREDICTION.md index 4720b1eb..649f3055 100644 --- a/docs/DISCOVERY_PREDICTION.md +++ b/docs/DISCOVERY_PREDICTION.md @@ -545,7 +545,7 @@ in the 20-member pilot panel, P(≥1 from family) ≈ 1 − (1 − P_candidate)^ | 3 | SEED-006 | INWKGIAAMAKKLL vars | 0.667 | 0.643 | ~14–22% | Balanced stability+novelty; mastoparan mechanism data | | 4 | SEED-009 | RRLPRPPYLPRP vars | 0.80+ | 0.467 | ~12–20% | Proline-rich intracellular (DnaK); orthogonal mechanism to all other seeds; 18 selected | | 5 | SEED-003 | RRWQWRMKKLG vars | 0.27 | 0.182 | ~8–16% | High ensemble (0.780-0.795) but poor serum stability; 16 selected | -| 6 | SEED-005 | KRFFKKIGSALKFA | 0.52 | 0.467 | ~8–14% | FF motif aids membrane insertion; 4 selected | +| 6 | SEED-005 | KRLFKKIGSALKFL (seed) | 0.52 | 0.467 | ~8–14% | Cecropin-magainin hybrid; best variant VAR_009 (KRFFKKIGSALKFA, FF motif) aids membrane insertion; 4 selected | > **Excluded from synthesis** (not in synthesis pool): > - SEED-004 (temporin, HIGH_CYTOTOX_RISK, GRAVY=+1.81): Correctly excluded by safety+cytotox gate @@ -671,7 +671,7 @@ Required to strengthen confidence: ### 3. Novelty Verification -The 45-sequence reference set used for novelty scoring does not represent the full landscape +The 72-sequence reference set used for novelty scoring does not represent the full landscape of known AMPs. Real-world novelty check required against: - APD3 (Antimicrobial Peptide Database v3): > 3,000 natural AMPs - DRAMP v3.0 (Data Repository of Antimicrobial Peptides): > 19,000 entries diff --git a/docs/METHODS.md b/docs/METHODS.md index 33e83af9..7f9f3b41 100644 --- a/docs/METHODS.md +++ b/docs/METHODS.md @@ -206,7 +206,7 @@ This score does not gate the ensemble — it is used only in the pilot panel ran ### 4.4 Novelty Score Novelty is computed as: `1 - max_similarity`, where max_similarity is the maximum normalized -Levenshtein similarity between the candidate and any sequence in the 45-sequence reference set +Levenshtein similarity between the candidate and any sequence in the 72-sequence reference set (`examples/known_reference/amp_curated_references.csv`). Normalized Levenshtein similarity: `1 - (edit_distance / max_length)`. @@ -214,7 +214,7 @@ Normalized Levenshtein similarity: `1 - (edit_distance / max_length)`. A novelty of 0.0 means the sequence is identical to a known reference. A novelty of 1.0 means no sequence in the reference set is similar at all. -**Limitation:** The reference set contains only 45 curated sequences. This is not a complete +**Limitation:** The reference set contains only 72 curated sequences. This is not a complete survey of known AMPs. Real-world novelty should be checked against APD3, CAMP, DRAMP, and UniProt antimicrobial sequences. @@ -375,7 +375,7 @@ power. |-------------|--------|--------| | Scoring not validated against lab data | Activity/safety scores may not correlate with assay results | Known; lab calibration needed | | Near-seed generation only | Misses genuinely novel AMP families | Known; future work | -| Small reference set | Novelty may be overestimated | Partially mitigated; 45 refs used | +| Small reference set | Novelty may be overestimated | Partially mitigated; 72 refs used | | Two scorers only | Disagreement is coarse uncertainty; not a calibrated posterior | Partially mitigated; Boman index added in v0.2 | | Helical amphipathicity assumption | Non-helical AMPs underscored | Known limitation | | No structural modeling | Cannot predict membrane interaction mode | Out of scope v0.1 | diff --git a/docs/WET_LAB_HANDOFF.md b/docs/WET_LAB_HANDOFF.md index 22332ebb..9e41931e 100644 --- a/docs/WET_LAB_HANDOFF.md +++ b/docs/WET_LAB_HANDOFF.md @@ -46,7 +46,7 @@ The pipeline uses four gates before a candidate is marked `selected: true`. |------|----------------|--------------|-----| | `min_novelty` | ≥ 0.20 | ≥ 0.05 | Near-duplicates waste budget on already-known peptides | | `max_safety_risk` → min safety | ≤ 0.70 → safety ≥ 0.30 | ≤ 0.40 → safety ≥ 0.60 | Phase 3 is the final synthesis batch — only clean candidates | -| `max_disagreement` | ≤ 0.40 | ≤ 0.30 | When physchem and Boman scoring diverge > threshold, both models are guessing | +| `max_disagreement` | ≤ 0.40 | ≤ 0.40 | When physchem and Boman scoring diverge > threshold, both models are guessing. Both configs use 0.40 — Trp-rich scaffolds (SEED-008) show disagreement ~0.37 due to mechanism divergence (interfacial insertion vs Boman electrostatic scale), not uncertainty | | Sequence validity | canonical AA only | same | Non-canonical residues are disqualified | A candidate must pass **all four gates** to be nominated. Failing any single gate → `selected: false`. @@ -163,7 +163,7 @@ It also activates G-proteins and has calmodulin-binding properties. If fewer than 10 candidates are nominated from a batch: 1. Check `disagreement` scores — if many candidates cluster near the configured `max_disagreement` - threshold (0.30 for phase3.yaml, 0.40 for pipeline.yaml), the two scorers may systematically + threshold (0.40 for both phase3.yaml and pipeline.yaml), the two scorers may systematically disagree for this peptide series. Consider whether to relax `max_disagreement` in a custom config (document the change and the scientific justification). 2. Check `novelty` scores — if the reference set covers your template region well, novelty will