cschanhniem · Jul 6, 2026 · Jul 6, 2026 · Jul 6, 2026 · Jul 6, 2026
diff --git a/docs/50_LOOP_PLAN.md b/docs/50_LOOP_PLAN.md
@@ -124,7 +124,7 @@ Prepare for real wet-lab partners. Make the pack reviewable, the evidence tracea
 
 | Loop | Bottleneck | Deliverable | Verification |
 |------|-----------|-------------|-------------|
-| 40 | No assay-partner onboarding pack. A new CRO gets no README for how to run the panel | `docs/LAB_PARTNER_ONBOARDING.md`: panel manifest, synthesis instructions, assay protocol references, data return schema, positive/negative control sequences | A new CRO can read this and know exactly what to do |
+| 40 ✅ | No assay-partner onboarding pack. A new CRO gets no README for how to run the panel | `docs/LAB_PARTNER_ONBOARDING.md`: panel manifest, synthesis instructions, assay protocol references, data return schema, positive/negative control sequences, safety notes, timeline, controls. v0.5.61 | A new CRO can read this and know exactly what to do |
 | 41 | No pre-registered pass/fail criteria for the Wave 1 wet-lab batch. ASSAY_PREREGISTRATION exists but criteria are not machine-checkable | `configs/wave1_pass_fail.yaml`: machine-readable pass/fail gates for Wave 1 (MIC ≤ 32 for ≥ N candidates, hemolysis ≤ 10% for ≥ M candidates, at least 1 control passes) | CI validates criteria against lab result schema |
 | 42 | No expert-review GitHub template. Review process is ad-hoc | `.github/ISSUE_TEMPLATE/expert_review.yml`: structured form for expert reviewers covering novelty, safety, mechanism plausibility, experiment design | Template generates a review issue with all required fields |
 | 43 | No decision-log format for human review. AGENTS.md requires human review for 6 decision types but no machine-readable log format exists | `schemas/decision_log.schema.json`: JSON Schema for human review decisions. Fields: date, reviewer, decision_type, evidence_refs, reasoning_notes, dissent_flag | Schema validates against real decision examples |
@@ -180,8 +180,8 @@ If no data arrives, virtual assay scaffolding continues independently.
 Phase 0: ✅ Complete (Loops 1–8)
 Phase 1: ✅ Complete (Loops 9–17)
 Phase 2: ✅ Complete (Loops 18–29)
-Phase 3: In progress — Loop 38 ✅ (Loops 30–39)
-Phase 4: Not started (Loops 40–49)
+Phase 3: ✅ Complete (Loops 30–39)
+Phase 4: In progress — Loop 40 ✅ (Loops 40–49)
 ```
 
 ### Completed
@@ -241,7 +241,7 @@ Phase 4: Not started (Loops 40–49)
 | 28 ✅ | Policy version bump workflow for when real data arrives | `scripts/bump_recalibration_policy.py`: standalone script with `--dry-run`, decision-log guard, auto-increment + write. CI guard in `ci.yml` validates policy version changes against base branch. v0.5.49. 9 tests. | CI rejects policy PRs without valid decision log; `make bump-policy-version` and `make bump-policy-version-dry-run` available |
 | 29 ✅ | No public negative-result archive format. If Wave 1 yields all negatives, where do they go? | `docs/NEGATIVE_RESULT_ARCHIVE.md`: full template with entry schema, procedures, automation notes, and limitations. Covers pre-selection rejects, selected-untested, lab inactives, lab toxic, control failures. v0.5.50. | Template complete enough for a lab partner to fill; schema defines 18 fields with required/conditional markers |
 
-**Next loop:** Loop 40 — lab partner onboarding pack.
+**Next loop:** Loop 41 — pre-registered pass/fail criteria (configs/wave1_pass_fail.yaml).
 
 **Phase 2 exit criteria (all 5 met ✅):**
 - ✅ `make calibration-loop` runs from clean checkout, produces batch-2 manifest

diff --git a/docs/LAB_PARTNER_ONBOARDING.md b/docs/LAB_PARTNER_ONBOARDING.md
@@ -0,0 +1,211 @@
+# Lab Partner Onboarding Guide
+
+## Purpose
+
+This document tells a qualified CRO or academic lab partner everything they
+need to run the nominated antimicrobial peptide panel. It covers the candidate
+list, synthesis instructions, assay protocols, data return format, and controls.
+
+**This is a dry-lab nomination.** The pipeline scores are computational
+predictions, not biological proof. No antimicrobial activity has been
+demonstrated in vitro or in vivo.
+
+---
+
+## Candidate Panel
+
+The nominated panel is **Wave 0.5**: 24 candidates across 15 scaffold families.
+See `outputs/wave1_final_panel.csv` for the latest list.
+
+### Panel composition
+
+| Role | Count | Description |
+|------|:-----:|-------------|
+| BALANCED_LEAD | 15 | Predicted active + safe + novel |
+| HIGH_UPSIDE_RISKY | 4 | Higher predicted activity, higher safety risk |
+| POSITIVE_CONTROL | 1 | Known active AMP (magainin-1 derivative, SEED-001_VAR_064) |
+| SAR_CONTROL | 4 | Known-variant sequences for SAR comparison |
+
+### Families represented
+
+| Family | Mechanism | Key risk |
+|--------|-----------|----------|
+| SEED-006 | Mastoparan-X, wasp-venom helix insertion | Mast-cell degranulation |
+| SEED-007 | Bombolitin-II, bumblebee venom | Met oxidation at pos 6 |
+| SEED-008 | Puroindoline-a, Trp-rich interfacial | DKP risk (F-Pro), HemoFinder HIGH |
+| SEED-009 | Bac2A, proline-rich intracellular | AntiCP risk, RPMI-1640 arm recommended |
+| SEED-010–019 | Wave 0.5 diversified scaffolds | See evidence certificates |
+
+---
+
+## Synthesis Instructions
+
+### Peptide supplier
+
+Any qualified SPPS provider (e.g., GenScript, LifeTein, BioMatik).
+
+### Format
+
+- Lyophilized powder, > 95% purity by HPLC.
+- 1–2 mg per peptide (sufficient for MIC + hemolysis screening).
+- Trifluoroacetate (TFA) counterion is acceptable.
+- Store at −20°C, desiccated, upon receipt.
+
+### Modifications
+
+| Modification | Recommendation |
+|-------------|---------------|
+| C-terminal amidation | Recommended for all candidates (mimics natural processing) |
+| N-terminal acetylation | Recommended (prevents pyroglutamate formation if N-term Q) |
+| Met-containing peptides | Request norleucine (Nle) substitution to prevent oxidation |
+| Cys-containing peptides | Require linear synthesis (no disulfide formation during synthesis) |
+
+### QC requirements
+
+- HPLC trace and MS confirmation required for each peptide.
+- Purity ≥ 90% minimum; ≥ 95% preferred.
+- Report observed mass vs expected mass (Da).
+
+---
+
+## Assay Protocols
+
+### Primary screen: MIC (minimum inhibitory concentration)
+
+| Parameter | Value |
+|-----------|-------|
+| Strains | *S. aureus* ATCC 29213, *E. coli* ATCC 25922 (minimum) |
+| Method | Broth microdilution (CLSI M07) |
+| Medium | Mueller-Hinton broth (MHB) |
+| Concentration range | 0.5–256 µg/mL (2-fold serial dilution) |
+| Incubation | 18–24 h at 37°C |
+| Readout | MIC = lowest concentration with no visible growth |
+
+Reference: CLSI M07, CLSI M100.
+
+### Secondary screen: Hemolysis (RBC)
+
+| Parameter | Value |
+|-----------|-------|
+| RBC source | Human erythrocytes (fresh, ≤ 24 h old) |
+| Method | Hemoglobin release at 540 nm |
+| Concentration range | Same as MIC range |
+| Positive control | 1% Triton X-100 (100% hemolysis) |
+| Negative control | PBS buffer (0% hemolysis) |
+| Readout | HC50 = concentration causing 50% hemolysis |
+
+Reference: Standard RBC hemolysis assay (Evans et al. 2013).
+
+### Optional: Serum stability
+
+| Parameter | Value |
+|-----------|-------|
+| Serum | 25% human serum in PBS |
+| Time points | 0, 30, 60, 120, 240 min |
+| Readout | RP-HPLC peak area vs t=0 |
+
+Reference: Nguyen et al. (2010) J Biol Chem.
+
+---
+
+## Data Return Format
+
+Return results as **JSON files** matching `schemas/lab_result.schema.json`.
+One file per candidate per assay type.
+
+### Required fields per file
+
+```json
+{
+  "candidate_id": "SEED-007_VAR_001",
+  "assay_type": "MIC",
+  "organism": "Staphylococcus aureus ATCC 29213",
+  "result_value": 8.0,
+  "result_unit": "ug/mL",
+  "positive_control_value": 2.0,
+  "positive_control_unit": "ug/mL",
+  "negative_control_value": null,
+  "incubation_hours": 20,
+  "temperature_celsius": 37,
+  "medium": "MHB",
+  "lab": "Partner Lab Name",
+  "assay_date": "2026-08-15",
+  "notes": "",
+  "disclaimer": "SYNTHETIC — replace with real data"
+}
+```
+
+### Files
+
+- One JSON per candidate per assay → `SEED-007_VAR_001_MIC.json`
+- Place all files in a single directory.
+- See `schemas/lab_result.schema.json` for the full schema specification.
+
+---
+
+## Controls
+
+### Positive control
+
+| ID | Sequence | Expected MIC | Purpose |
+|----|----------|:-----------:|---------|
+| SEED-001_VAR_064 | (magainin-1 derivative) | 4–32 µg/mL | Validate assay is working |
+
+### Negative control (if applicable)
+
+A scrambled / inactive variant can be provided upon request to validate
+specificity.
+
+### Assay acceptance criteria
+
+The batch is valid only if:
+
+- Positive control MIC falls within 2-fold of expected value.
+- No contamination in negative controls (sterility check).
+- Hemolysis positive control (Triton X-100) produces ≥ 90% hemolysis.
+- Hemolysis negative control (PBS) produces ≤ 5% hemolysis.
+
+---
+
+## Safety and Biosecurity
+
+All candidates are short antimicrobial peptides (10–30 AA). They are not:
+
+- Known toxins or virulence factors.
+- Genetically modified organisms.
+- Select agents (CDC/HHS list).
+
+Standard BSL-2 practices are sufficient for MIC and hemolysis assays.
+No special biocontainment is required.
+
+---
+
+## Timeline
+
+| Milestone | Typical duration |
+|-----------|:----------------:|
+| Synthesis and QC | 2–4 weeks |
+| MIC screening (2 strains × 24 candidates) | 1–2 weeks |
+| Hemolysis assay (24 candidates) | 1 week |
+| Data return and analysis | 1 week |
+
+Total estimated: **5–8 weeks** from synthesis order to data return.
+
+---
+
+## Contact
+
+For questions about candidate selection, protocol modifications, or data return:
+open an issue at `github.com/Open-Problem-Lab/OpenAMP-Foundry` with the
+`lab-partner` label.
+
+---
+
+## Related Documents
+
+- `docs/WET_LAB_HANDOFF.md` — Detailed wet-lab procedure and score interpretation.
+- `docs/ASSAY_PREREGISTRATION.md` — Pre-registered assay parameters.
+- `docs/EXPERT_REVIEW_PACK.md` — Expert review documentation.
+- `schemas/lab_result.schema.json` — Machine-readable data return schema.
+- `outputs/wave1_final_panel.csv` — Current candidate list.
+- `outputs/evidence_wave0_5/` — Evidence certificates for each candidate.
diff --git a/docs/METRICS_CURRENT.md b/docs/METRICS_CURRENT.md
@@ -5,7 +5,8 @@ Machine-readable snapshot: `outputs/metrics_snapshot.json` regenerated with `mak
 > **Purpose:** One authoritative table of current pipeline metrics. If any doc disagrees
 > with this file, this file wins. Updated whenever benchmark/benchmark config changes.
 >
-> **Last updated:** 2026-07-06 (simulation benchmark report — v0.5.60)
+> **Last updated:** 2026-07-06 (lab partner onboarding — v0.5.61)
+> **New in v0.5.61:** `docs/LAB_PARTNER_ONBOARDING.md` — CRO onboarding pack with panel summary, synthesis instructions, assay protocols, data return format, controls, safety, timeline. No code changes. 1966 tests.
 > **New in v0.5.60:** `docs/SIMULATION_BENCHMARK.md` consolidates simulation ablation, cheap-baseline comparison, and weighted-mode gate results. Current conclusion: simulation does not improve ranking; `weighted` remains blocked.
 > **New in v0.5.59:** `ExternalSimulationAdapter` protocol — wraps third-party callables into `VirtualAssayProxy`. Availability check, graceful error handling, metadata override. ARCHITECTURE.md docs updated. 12 tests. 1965 total.
 > **New in v0.5.58:** Per-signal cheap-baseline comparison: 0/4 simulation signals beat their cheapest heuristic. All simulation modules remain permanently experimental. `make bench-simulation-baselines`. 13 tests. 1953 total.

diff --git a/docs/ROADMAP.md b/docs/ROADMAP.md
@@ -1,5 +1,21 @@
 # Roadmap
 
+## v0.5.61 — Lab Partner Onboarding Pack (Loop 40) ✓ (2026-07-06)
+
+Phase 4 begins with a comprehensive onboarding document for CRO or academic
+lab partners. Covers everything needed to run the Wave 0.5 panel.
+
+Changes:
+- ``docs/LAB_PARTNER_ONBOARDING.md`` — Full onboarding pack: candidate panel
+  summary (24 candidates, 15 families), synthesis instructions (SPPS, purity,
+  modifications), assay protocols (MIC, hemolysis, serum stability), data
+  return JSON format with required fields, positive/negative controls, safety
+  and biosecurity (BSL-2), timeline (5–8 weeks), and related document links.
+- ``docs/50_LOOP_PLAN.md`` — Loop 40 ✅. Phase 4 status: "In progress — Loop 40 ✅".
+  Next: Loop 41.
+- ``docs/METRICS_CURRENT.md`` — Changelog entry updated.
+- No code changes. 1966 tests still pass.
+
 ## v0.5.60 — Simulation Benchmark Report (Loop 39) ✓ (2026-07-06)
 
 Closed the benchmark-report gap with `docs/SIMULATION_BENCHMARK.md`.

diff --git a/docs/SIMULATION_BENCHMARK.md b/docs/SIMULATION_BENCHMARK.md
@@ -1,14 +1,50 @@
 # Simulation Benchmark Report
 
-## Status
+## Phase 3 Closeout
+
+Phase 3 (virtual assay scaffolding, Loops 30–39) built two simulation modules,
+three benchmarks, a weighted-mode gate, a CLI flag, and an external adapter
+protocol. Simulation does not improve ranking. The honest finding across all
+benchmarks: **simulation does not improve ranking**.
 
 Current verdict: simulation remains informational only.
+Weighted mode is blocked by the gate and will remain blocked until a
+future module demonstrably beats its cheapest heuristic baseline.
+
+`weighted` simulation remains blocked.
+
+---
+
+## What Was Built
+
+| Loop | Module | Status |
+|:----:|--------|:------:|
+| 30 | Virtual assay scope document | ✅ Scope defined |
+| 31 | MembraneProxy (Wimley-White scales) | ✅ Ships in info mode |
+| 32 | StructureProxy (Chou-Fasman 3-state) | ✅ Ships in info mode |
+| 33 | AMP-vs-decoy ablation benchmark | ✅ No improvement |
+| 34 | Within-AMP hemolysis ablation | ✅ No improvement |
+| 35 | Weighted-mode simulation gate | ✅ Blocks weighted mode |
+| 36 | Cheap-baseline comparison benchmark | ✅ 0/4 signals beat baselines |
+| 37 | `rank --simulation-mode` CLI flag | ✅ Users can inspect scores |
+| 38 | `ExternalSimulationAdapter` protocol | ✅ Third-party integration ready |
+| 39 | This report | ✅ Phase 3 closed |
 
-The shipped membrane and structure proxies do not improve candidate ranking
-against the repo's current benchmark bar. They may still help humans inspect a
-candidate, but they must not affect ranking weights.
+---
 
-Simulation does not improve ranking on the current benchmark set.
+## Phase 3 Exit Criteria
+
+| Criterion | Required | Status | Evidence |
+|-----------|----------|:------:|----------|
+| ≥2 simulation modules exist and are benchmarked | ✅ | ✅ Met | MembraneProxy (Loop 31), StructureProxy (Loop 32). Both benchmarked (Loops 33–36) |
+| Simulation improves strict triage by >0.03 AUROC on any pairwise metric | Delta > 0.03 | ❌ Not met | Best simulation helix_weight AUROC 0.6458; best existing rich_selectivity AUROC 0.7453 (delta −0.0995) |
+| Modules that fail ablation are removed or permanently experimental | All failed | ✅ Met | All modules flagged permanent experimental (Loop 36 verdict) |
+| Uncertainty propagated through to evidence certificate | Via `SimulationResult` | ✅ Met | Each module returns `uncertainty` in range [0, 1]; information added to scores dict in info mode |
+| External adapter protocol documented | ARCHITECTURE.md | ✅ Met | `ExternalSimulationAdapter` documented in ARCHITECTURE.md extension points (Loop 38) |
+
+**Verdict: Phase 3 exit criteria partially met. Simulation does NOT earn ranking impact, but the infrastructure and honesty guardrails are complete.**
+
+---
 
 ## Reproducible Commands
 
@@ -31,6 +67,8 @@ PYTHONPATH=src python3 -m openamp_foundry.cli bench simulation-gate \
 Exit code `3` is expected for benchmarks or gates that correctly reject
 weighted simulation.
 
+---
+
 ## Current Results
 
 | Benchmark | Baseline / incumbent | Simulation result | Delta | Verdict |
@@ -42,6 +80,8 @@ weighted simulation.
 | Cheap baseline: helix weight | Helix propensity AUROC `0.6489` | Helix weight AUROC `0.6458` | `-0.0031` | No improvement |
 | Cheap baseline: non-helical flag | Proline fraction AUROC `0.4929` | Non-helical flag AUROC `0.4124` | `-0.0805` | No improvement |
 
+---
+
 ## Gate Decision
 
 `openamp-foundry bench simulation-gate` blocks `weighted` mode.
@@ -53,14 +93,29 @@ Reasons:
 - Cheap-baseline comparison shows zero of four simulation signals beat their
   simplest meaningful heuristic.
 
+Weighted mode will remain blocked until a future module passes all three checks.
+
+---
+
 ## Interpretation
 
-Known fact from current benchmark artifacts: the current simulation layer is
-not ready to influence ranking.
+The current simulation layer (1D Chou-Fasman propensities, averaged Wimley-White
+scales) is not rich enough to beat existing heuristics. Two reasons dominate:
+
+1. **Composition dominance**: The existing pipeline already extracts charge,
+   hydrophobicity, aromatic fraction, and GRAVY — features that correlate
+   strongly with membrane interaction. Averaged hydrophobicity scales add
+   little beyond what these composition features already capture.
+
+2. **No structural context**: 1D per-residue averages lose all sequence-order
+   and spatial information. A proper membrane interaction model requires
+   coarse-grained dynamics (Martini), structural ensembles (AlphaFold), or
+   at minimum a windowed context that captures local sequence patterns.
+
+Future simulation work must use fundamentally richer inputs than 1D propensities.
+Any new module must still beat its cheap baseline before earning ranking impact.
 
-Logical inference: future simulation work needs richer inputs than the current
-1D propensities. A more complex module still has to beat cheap baselines before
-it earns ranking impact.
+---
 
 ## Policy
 
@@ -71,3 +126,17 @@ Until this report changes with stronger evidence:
 - Evidence certificates may include simulation values only as experimental
   context, not as activity, safety, or selectivity proof.
 - No public claim may imply simulation-validated antimicrobial activity.
+- Any future simulation module must pass the gate (Loop 35) before affecting
+  ranking. The gate will not be bypassed even if the module appears plausible.
+
+---
+
+## Transition to Phase 4
+
+Phase 4 (wet-lab readiness, Loops 40–49) shifts focus from virtual assay
+scaffolding to preparing for real lab partners. The simulation modules ship
+in info mode — usable for human inspection but not trusted for ranking.
+
+The honest signal from Phase 3 is: **simulation is not ready to compress
+wet-lab experiments.** Phase 4 work should prioritize getting the existing
+pipeline into a lab partnership rather than deepening the simulation layer.