---
phase: 06-validation
plan: 03
subsystem: validation
tags: [comprehensive-validation, cli-validate, validation-report, weight-tuning, unit-tests]
dependency_graph:
  requires: [06-01-negative-controls-recall, 06-02-sensitivity-analysis]
  provides: [comprehensive-validation-report, cli-validate-command, validation-tests]
  affects: [validation-workflow-completion]
tech_stack:
  added: []
  patterns: [comprehensive-validation-pipeline, weight-tuning-recommendations, cli-orchestration]
key_files:
  created:
    - src/usher_pipeline/scoring/validation_report.py
    - src/usher_pipeline/cli/validate_cmd.py
    - tests/test_validation.py
  modified:
    - src/usher_pipeline/cli/main.py
    - src/usher_pipeline/scoring/__init__.py
decisions:
  - "Comprehensive validation report combines positive, negative, and sensitivity prongs in single Markdown document"
  - "Weight tuning recommendations are guidance-only with critical circular validation warnings"
  - "CLI validate command follows score_cmd.py pattern with --force, --skip-sensitivity, --output-dir, --top-n options"
  - "Tests use synthetic DuckDB data with designed score patterns (known genes high, housekeeping low)"
  - "Validation report saved to {data_dir}/validation/validation_report.md by default"
metrics:
  duration_minutes: 5
  completed_date: 2026-02-12
  tasks_completed: 2
  files_created: 3
  files_modified: 2
  commits: 2
---

# Phase 6 Plan 03: Comprehensive Validation Report & CLI Summary

CLI validate command orchestrating full validation pipeline (positive controls, negative controls, sensitivity analysis) with comprehensive Markdown report and weight tuning recommendations.

## Tasks Completed

### Task 1: Create comprehensive validation report and CLI validate command
**Status:** Complete
**Commit:** 10f19f8
**Files:** src/usher_pipeline/scoring/validation_report.py, src/usher_pipeline/cli/validate_cmd.py, src/usher_pipeline/cli/main.py, src/usher_pipeline/scoring/__init__.py

**Created validation_report.py** with comprehensive report generation:

- **generate_comprehensive_validation_report()**: Multi-section Markdown report combining all three validation prongs
  - Section 1: Positive Control Validation (median percentile, recall@k table, per-source breakdown, pass/fail)
  - Section 2: Negative Control Validation (median percentile, top quartile count, in-HIGH-tier count, pass/fail)
  - Section 3: Sensitivity Analysis (Spearman rho table by layer × delta, stability verdict, most/least sensitive layers)
  - Section 4: Overall Validation Summary (all-pass/partial-fail/fail verdict with interpretation)
  - Section 5: Weight Tuning Recommendations (targeted suggestions based on validation results)

- **recommend_weight_tuning()**: Analyzes validation results and provides weight adjustment guidance
  - All validations pass → "Current weights are validated. No tuning recommended."
  - Positive controls fail → Suggest increasing weights for layers where known genes score highly
  - Negative controls fail → Suggest examining layers boosting housekeeping genes, reducing generic layer weights
  - Sensitivity unstable → Identify most sensitive layer, suggest reducing its weight
  - **CRITICAL WARNING:** Documents circular validation risk (post-validation tuning invalidates controls)
  - Provides best practices: independent validation set, document rationale, prefer a priori weights

- **save_validation_report()**: Persists report to file with parent directory creation

**Created validate_cmd.py** CLI command following score_cmd.py pattern:

- Click command `validate` with options:
  - `--force`: Re-run even if validation checkpoint exists
  - `--skip-sensitivity`: Skip sensitivity analysis for faster iteration
  - `--output-dir`: Custom output directory (default: {data_dir}/validation)
  - `--top-n`: Top N genes for sensitivity analysis (default: 100)

- Pipeline steps:
  1. Load configuration and initialize store
  2. Check scored_genes checkpoint exists (error if not - must run `score` first)
  3. Run positive control validation (validate_positive_controls_extended)
  4. Run negative control validation (validate_negative_controls)
  5. Run sensitivity analysis (unless --skip-sensitivity) - run_sensitivity_analysis + summarize_sensitivity
  6. Generate comprehensive validation report (generate_comprehensive_validation_report)
  7. Save report to output_dir/validation_report.md and provenance sidecar

- Styled output with click.echo patterns (green for success, yellow for warnings, red for errors, bold for step headers)
- Provenance tracking: record_step for each validation phase with metrics
- Final summary: displays overall pass/fail, recall@10%, housekeeping median percentile, sensitivity stability

**Updated main.py:**
- Imported validate from validate_cmd
- Added `cli.add_command(validate)` following existing pattern

**Updated scoring.__init__.py:**
- Added validation_report imports: generate_comprehensive_validation_report, recommend_weight_tuning, save_validation_report
- Added all 3 functions to __all__ exports

**Verification:** Both verification commands passed:
- `python -c "from usher_pipeline.cli.validate_cmd import validate; print(f'Command name: {validate.name}'); print('OK')"` → OK
- `python -c "from usher_pipeline.cli.main import cli; assert 'validate' in cli.commands"` → OK

### Task 2: Create unit tests for all validation modules
**Status:** Complete
**Commit:** 5879ae9
**Files:** tests/test_validation.py

**Created test_validation.py** with 13 comprehensive tests using synthetic DuckDB data:

**Test helper:**
- **create_synthetic_scored_db()**: Creates DuckDB with gene_universe (20 genes) and scored_genes table
  - Designed scores ensure known cilia genes (MYO7A, IFT88, BBS1) get high scores (0.85-0.92)
  - Housekeeping genes (GAPDH, ACTB, RPL13A) get low scores (0.12-0.20)
  - Filler genes get mid-range scores (0.35-0.58)
  - Includes all 6 layer scores and quality_flag
  - Creates known_genes table with 3 genes (1 OMIM, 2 SYSCILIA)

**Tests for negative controls (4 tests):**
1. **test_compile_housekeeping_genes_structure**: Verifies compile_housekeeping_genes() returns DataFrame with 13 genes, correct columns (gene_symbol, source, confidence), all confidence=HIGH, all source=literature_validated

2. **test_compile_housekeeping_genes_known_genes_present**: Asserts GAPDH, ACTB, RPL13A, TBP are in gene_symbol column

3. **test_validate_negative_controls_with_synthetic_data**: Uses synthetic DB where housekeeping genes score low, asserts validation_passed=True, median_percentile < 0.5

4. **test_validate_negative_controls_inverted_logic**: Creates DB where housekeeping genes score HIGH (artificial scenario), asserts validation_passed=False

**Tests for recall@k (1 test):**
5. **test_compute_recall_at_k**: Uses synthetic DB, asserts recall@k returns dict with recalls_absolute and recalls_percentage keys. With 3 known genes in dataset (out of 38 total from compile_known_genes), recall@100 = 3/38 = 0.0789

**Tests for weight perturbation (3 tests):**
6. **test_perturb_weight_renormalizes**: Perturbs gnomad by +0.10, asserts weights still sum to 1.0 within 1e-6 tolerance

7. **test_perturb_weight_large_negative**: Perturbs by -0.25 (more than weight value), asserts weight >= 0.0 (clamped) and sum = 1.0

8. **test_perturb_weight_invalid_layer**: Asserts perturb_weight with layer="nonexistent" raises ValueError

**Tests for validation report (5 tests):**
9. **test_generate_comprehensive_validation_report_format**: Passes mock metrics dicts, asserts report contains expected sections ("Positive Control", "Negative Control", "Sensitivity Analysis", "Weight Tuning")

10. **test_recommend_weight_tuning_all_pass**: Passes metrics indicating all validations pass, asserts response contains "No tuning recommended"

11. **test_recommend_weight_tuning_positive_fail**: Passes metrics with positive controls failed, asserts response contains "Known Gene Ranking Issue" or "Positive Control"

12. **test_recommend_weight_tuning_negative_fail**: Passes metrics with negative controls failed, asserts response contains "Housekeeping" or "Negative Control"

13. **test_recommend_weight_tuning_sensitivity_fail**: Passes metrics with sensitivity unstable, asserts response contains "Sensitivity" or "gnomad"

**Verification:** All 13 tests passed:
```
tests/test_validation.py::test_compile_housekeeping_genes_structure PASSED
tests/test_validation.py::test_compile_housekeeping_genes_known_genes_present PASSED
tests/test_validation.py::test_validate_negative_controls_with_synthetic_data PASSED
tests/test_validation.py::test_validate_negative_controls_inverted_logic PASSED
tests/test_validation.py::test_compute_recall_at_k PASSED
tests/test_validation.py::test_perturb_weight_renormalizes PASSED
tests/test_validation.py::test_perturb_weight_large_negative PASSED
tests/test_validation.py::test_perturb_weight_invalid_layer PASSED
tests/test_validation.py::test_generate_comprehensive_validation_report_format PASSED
tests/test_validation.py::test_recommend_weight_tuning_all_pass PASSED
tests/test_validation.py::test_recommend_weight_tuning_positive_fail PASSED
tests/test_validation.py::test_recommend_weight_tuning_negative_fail PASSED
tests/test_validation.py::test_recommend_weight_tuning_sensitivity_fail PASSED
======================== 13 passed, 1 warning in 0.79s =========================
```

## Deviations from Plan

None - plan executed exactly as written.

## Verification Results

All verification checks passed:

1. `python -c "from usher_pipeline.cli.validate_cmd import validate; print(f'Command name: {validate.name}'); print('OK')"` → OK
2. `python -c "from usher_pipeline.cli.main import cli; assert 'validate' in cli.commands"` → OK
3. `python -m pytest tests/test_validation.py -v` → 13 passed, 0 failed

## Success Criteria

- [x] CLI `validate` command runs positive + negative + sensitivity validations and generates comprehensive report
- [x] Validation report includes all three prongs with pass/fail verdicts and weight tuning recommendations
- [x] Unit tests cover negative controls, recall@k, perturbation, and report generation
- [x] All tests pass with synthetic data
- [x] validate command registered in main CLI

## Key Files

### Created
- **src/usher_pipeline/scoring/validation_report.py** (410 lines)
  - Comprehensive validation report generation combining all three validation prongs
  - Exports: generate_comprehensive_validation_report, recommend_weight_tuning, save_validation_report

- **src/usher_pipeline/cli/validate_cmd.py** (408 lines)
  - CLI validate command orchestrating full validation pipeline
  - Exports: validate (Click command)

- **tests/test_validation.py** (478 lines)
  - Unit tests for negative controls, recall@k, sensitivity, and validation report
  - 13 tests with synthetic DuckDB fixture

### Modified
- **src/usher_pipeline/cli/main.py** (+2 lines)
  - Added validate command import and registration

- **src/usher_pipeline/scoring/__init__.py** (+7 lines)
  - Added validation_report module exports

## Integration Points

**Depends on:**
- Phase 06-01: Negative control validation (validate_negative_controls) and positive control validation (validate_positive_controls_extended, compute_recall_at_k)
- Phase 06-02: Sensitivity analysis (run_sensitivity_analysis, summarize_sensitivity)
- Phase 04-02: scored_genes checkpoint (validation requires scoring to be complete)

**Provides:**
- Comprehensive validation report combining all three validation prongs
- CLI `validate` command for user-facing validation workflow
- Unit test coverage for all validation modules

**Affects:**
- Phase 6 completion: This is the final plan in validation phase
- User workflow: Provides `usher-pipeline validate` command for validation step

## Technical Notes

**Comprehensive Validation Report Design:**

The report combines three complementary validation approaches:
1. **Positive controls** (Plan 06-01): Known genes should rank high → validates sensitivity
2. **Negative controls** (Plan 06-01): Housekeeping genes should rank low → validates specificity
3. **Sensitivity analysis** (Plan 06-02): Rankings stable under perturbations → validates robustness

If all three pass: scoring system is sensitive, specific, and robust.

**Overall Validation Verdict Logic:**
- **All pass** → "ALL VALIDATIONS PASSED ✓" (scientifically defensible)
- **Pos + Neg pass, Sensitivity fail** → "PARTIAL PASS (Sensitivity Unstable)" (directionally correct but may need weight tuning)
- **Pos pass, Neg fail** → "PARTIAL PASS (Specificity Issue)" (sensitive but not specific)
- **Pos fail** → "VALIDATION FAILED ✗" (fundamental scoring issues)

**Weight Tuning Recommendations Philosophy:**

Recommendations are **guidance**, not automatic actions. They suggest:
- Which layers to adjust (increase/decrease weights)
- Why adjustments are needed (based on validation failures)
- How to interpret failures (specificity vs sensitivity vs stability)

**CRITICAL WARNING** included in all recommendations:
- Post-validation tuning introduces **circular validation risk**
- If weights are tuned based on validation results, those same controls cannot validate the tuned weights
- Best practices: independent validation set, document rationale, prefer a priori weights

This prevents the pitfall identified in 06-RESEARCH.md: "Tuning weights to maximize known gene recall, then using known gene recall as validation."

**CLI validate Command Design:**

Follows established pattern from score_cmd.py:
1. Click command with options (--force, --skip-sensitivity, --output-dir, --top-n)
2. Step-by-step pipeline with styled output (bold headers, colored status)
3. Checkpoint-restart support (skips if validation_report.md exists unless --force)
4. Provenance tracking for all steps (record_step for each validation phase)
5. Final summary with overall status and key metrics
6. Error handling with sys.exit(1) on failures

**Test Design Philosophy:**

All tests use **synthetic DuckDB data** with **designed score patterns**:
- Known genes get high scores (0.85-0.92) → positive controls should pass
- Housekeeping genes get low scores (0.12-0.20) → negative controls should pass
- Deterministic scores enable precise assertions

Tests cover:
- **Happy path**: Validations pass with expected data
- **Inverted logic**: Validations fail when data is wrong (housekeeping genes high)
- **Edge cases**: Large negative perturbations, invalid layer names
- **Format verification**: Report contains expected sections
- **Recommendation logic**: Different tuning suggestions for different failure modes

**Usage Pattern:**

```bash
# Full validation pipeline
usher-pipeline validate

# Skip sensitivity analysis (faster iteration)
usher-pipeline validate --skip-sensitivity

# Custom output directory
usher-pipeline validate --output-dir results/validation

# More genes for sensitivity (default 100)
usher-pipeline validate --top-n 200

# Force re-run
usher-pipeline validate --force
```

**Expected Workflow:**

1. User runs `usher-pipeline score` (Phase 04-03)
2. User runs `usher-pipeline validate` (this plan)
3. User reviews validation report at {data_dir}/validation/validation_report.md
4. If all pass: proceed to candidate prioritization
5. If failures: review weight tuning recommendations, adjust weights with biological justification, re-run

**Phase 6 Completion:**

This plan completes Phase 6 (Validation). All three plans executed:
- 06-01: Negative controls and recall@k (2 min)
- 06-02: Sensitivity analysis (3 min)
- 06-03: Comprehensive validation report and CLI (5 min)

Total Phase 6 duration: 10 minutes across 3 plans.

## Self-Check: PASSED

**Created files verified:**
- [x] src/usher_pipeline/scoring/validation_report.py exists (410 lines)
- [x] src/usher_pipeline/cli/validate_cmd.py exists (408 lines)
- [x] tests/test_validation.py exists (478 lines)

**Modified files verified:**
- [x] src/usher_pipeline/cli/main.py updated with validate import and registration
- [x] src/usher_pipeline/scoring/__init__.py updated with validation_report exports

**Commits verified:**
- [x] 10f19f8: Task 1 commit exists (comprehensive validation report and CLI validate command)
- [x] 5879ae9: Task 2 commit exists (unit tests for all validation modules)

**Functionality verified:**
- [x] validate command imports correctly (Command name: validate, OK)
- [x] validate registered in CLI (CLI commands includes 'validate', OK)
- [x] All 13 tests pass (pytest reports 13 passed, 0 failed)

All claims in summary verified against actual implementation.