docs(03-05): complete animal model phenotype evidence layer plan

- SUMMARY.md: Ortholog-mapped animal evidence from MGI/ZFIN/IMPC - Confidence-weighted scoring (mouse +0.4, zebrafish +0.3, IMPC +0.3) - 14/14 tests passing: ortholog confidence, keyword filtering, NULL preservation - Deviations: Schema mismatches, NULL handling, polars deprecations auto-fixed - Duration: 10 minutes, 2 tasks, 8 files, 2 commits
2026-02-11 19:08:45 +08:00
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+---
+phase: 03-core-evidence-layers
+plan: 05
+subsystem: evidence-layers
+tags: [animal-models, phenotypes, orthologs, evidence, MGI, ZFIN, IMPC]
+dependency_graph:
+  requires:
+    - Gene universe (01-02)
+    - DuckDB persistence layer (01-03)
+    - CLI framework (01-04)
+  provides:
+    - animal_model_phenotypes DuckDB table
+    - Ortholog mapping with confidence scoring (HCOP)
+    - Sensory/cilia phenotype filtering
+    - Animal model evidence scoring (0-1 normalized)
+  affects:
+    - Future scoring integration (Phase 04)
+tech_stack:
+  added:
+    - HCOP ortholog database integration
+    - MGI phenotype report parsing
+    - ZFIN phenotype data integration
+    - IMPC SOLR API queries with batching
+  patterns:
+    - Ortholog confidence tiering (HIGH/MEDIUM/LOW based on support count)
+    - Multi-organism evidence aggregation
+    - NULL preservation for unmapped orthologs
+    - Confidence-weighted scoring
+key_files:
+  created:
+    - src/usher_pipeline/evidence/animal_models/__init__.py: Module exports
+    - src/usher_pipeline/evidence/animal_models/models.py: AnimalModelRecord with ortholog fields
+    - src/usher_pipeline/evidence/animal_models/fetch.py: Ortholog and phenotype data retrieval
+    - src/usher_pipeline/evidence/animal_models/transform.py: Keyword filtering and confidence scoring
+    - src/usher_pipeline/evidence/animal_models/load.py: DuckDB persistence with provenance
+    - tests/test_animal_models.py: 10 unit tests for scoring and filtering
+    - tests/test_animal_models_integration.py: 4 integration tests for full pipeline
+  modified:
+    - src/usher_pipeline/cli/evidence_cmd.py: Added animal-models subcommand
+decisions:
+  - decision: "Ortholog confidence based on HCOP support count (HIGH: 8+, MEDIUM: 4-7, LOW: 1-3)"
+    rationale: "Multi-database agreement indicates stronger ortholog relationship, affects scoring weight"
+    alternatives: ["Flat weighting (rejected - ignores quality signal)", "Binary threshold (rejected - loses granularity)"]
+  - decision: "For one-to-many orthologs, select highest confidence (not aggregate)"
+    rationale: "Best-supported ortholog more likely correct, avoids phenotype dilution from paralog mis-mapping"
+    alternatives: ["Keep all (rejected - complex aggregation)", "Average confidence (rejected - noise amplification)"]
+  - decision: "NULL score for genes without orthologs (not zero)"
+    rationale: "Preserves NULL pattern: no ortholog = unknown animal evidence, not zero evidence"
+    alternatives: ["Score as 0 (rejected - conflates absent data with negative evidence)"]
+  - decision: "Keyword-based phenotype filtering (not ontology traversal)"
+    rationale: "Simpler implementation, sufficient for sensory/cilia relevance, avoids MP/ZP ontology complexity"
+    alternatives: ["Full ontology walk (rejected - overkill for MVP)", "Pre-curated term lists (rejected - maintenance burden)"]
+  - decision: "Composite scoring: mouse +0.4, zebrafish +0.3, IMPC +0.3, confidence-weighted"
+    rationale: "Mouse more studied (higher weight), zebrafish complements, IMPC provides independent confirmation"
+    alternatives: ["Equal weights (rejected - ignores organism study depth)", "Max score (rejected - doesn't reward multi-organism)"]
+  - decision: "Phenotype count scaling via log2 (diminishing returns)"
+    rationale: "Rewards multiple phenotypes but prevents linear inflation from comprehensive knockouts"
+    alternatives: ["Linear scaling (rejected - inflates well-studied genes)", "Binary flag (rejected - ignores phenotype richness)"]
+metrics:
+  duration_minutes: 10
+  tasks_completed: 2
+  files_created: 7
+  files_modified: 1
+  tests_added: 14
+  commits: 2
+  completed_date: "2026-02-11"
+---
+
+# Phase 03 Plan 05: Animal Model Phenotype Evidence Summary
+
+**One-liner:** Ortholog-mapped animal model evidence from MGI/ZFIN/IMPC with confidence-weighted scoring (HIGH/MEDIUM/LOW), sensory/cilia keyword filtering, and multi-organism aggregation (mouse +0.4, zebrafish +0.3, IMPC +0.3).
+
+## What Was Built
+
+Implemented the animal model phenotypes evidence layer, retrieving knockout/perturbation phenotypes from three sources, mapping human genes to mouse and zebrafish orthologs with confidence scoring, filtering for sensory/cilia relevance, and scoring with ortholog quality weighting:
+
+1. **Data Models (models.py)**
+   - AnimalModelRecord pydantic model with:
+     - Ortholog fields: mouse_ortholog, zebrafish_ortholog with confidence (HIGH/MEDIUM/LOW)
+     - Phenotype flags: has_mouse_phenotype, has_zebrafish_phenotype, has_impc_phenotype
+     - Counts and categories: sensory_phenotype_count, phenotype_categories (semicolon-separated)
+     - Normalized score: animal_model_score_normalized (0-1 range)
+   - SENSORY_MP_KEYWORDS and SENSORY_ZP_KEYWORDS: keyword lists for phenotype filtering
+   - Table name constant: ANIMAL_TABLE_NAME = "animal_model_phenotypes"
+
+2. **Data Fetching (fetch.py)**
+   - `fetch_ortholog_mapping()`: Downloads HCOP human-mouse and human-zebrafish ortholog data
+     - Confidence assignment: HIGH (8+ supporting databases), MEDIUM (4-7), LOW (1-3)
+     - One-to-many handling: selects ortholog with highest support count
+     - Returns DataFrame with gene_id, orthologs, and confidence columns
+   - `fetch_mgi_phenotypes()`: Retrieves mouse phenotypes from MGI gene-phenotype report
+   - `fetch_zfin_phenotypes()`: Retrieves zebrafish phenotypes from ZFIN bulk download
+   - `fetch_impc_phenotypes()`: Queries IMPC SOLR API in batches (50 genes at a time with retry)
+   - All with httpx streaming downloads, tenacity retry, and structured logging
+
+3. **Data Transformation (transform.py)**
+   - `filter_sensory_phenotypes()`: Case-insensitive keyword matching against MP/ZP terms
+     - Filters for hearing, deaf, vestibular, balance, retina, vision, cochlea, stereocilia, cilia, etc.
+     - Handles NULL term values gracefully (skip filtering if all NULL)
+   - `score_animal_evidence()`: Confidence-weighted composite scoring
+     - Formula: base_score = sum of organism contributions weighted by confidence
+     - Mouse: +0.4 × confidence_weight (HIGH=1.0, MEDIUM=0.7, LOW=0.4)
+     - Zebrafish: +0.3 × confidence_weight
+     - IMPC: +0.3 (independent confirmation bonus)
+     - Phenotype count scaling: × log2(count + 1) / log2(max_count + 1) for diminishing returns
+     - Clamped to [0, 1], NULL if no ortholog mapping
+   - `process_animal_model_evidence()`: End-to-end pipeline orchestration
+     - Fetches orthologs → fetches phenotypes → filters sensory → aggregates → scores → returns
+
+4. **DuckDB Persistence (load.py)**
+   - `load_to_duckdb()`: Saves animal_model_phenotypes table with provenance
+     - Records ortholog coverage (mouse/zebrafish counts)
+     - Records confidence distributions (HIGH/MEDIUM/LOW breakdowns)
+     - Records mean sensory phenotype count
+     - Idempotent CREATE OR REPLACE pattern
+   - `query_sensory_phenotype_genes()`: Helper for querying by score threshold
+
+5. **CLI Integration (evidence_cmd.py)**
+   - `animal-models` subcommand following evidence layer pattern
+     - Checkpoint-restart: skips if animal_model_phenotypes table exists
+     - --force flag for reprocessing
+     - Loads gene universe from DuckDB
+     - Calls process_animal_model_evidence()
+     - Saves provenance sidecar to data/animal_models/phenotypes.provenance.json
+     - Displays summary: ortholog coverage, sensory phenotype counts, top 10 scoring genes
+
+## Tests
+
+**14 tests total (all passing):**
+
+### Unit Tests (10)
+- `test_ortholog_confidence_high`: 8+ supporting sources → HIGH confidence
+- `test_ortholog_confidence_low`: 1-3 supporting sources → LOW confidence
+- `test_one_to_many_best_selected`: One-to-many mappings → highest confidence kept
+- `test_sensory_keyword_match`: "hearing loss" matches SENSORY_MP_KEYWORDS
+- `test_non_sensory_filtered`: "increased body weight" filtered out
+- `test_score_with_confidence_weighting`: HIGH confidence scores higher than LOW
+- `test_score_null_no_ortholog`: No ortholog → NULL score (not zero)
+- `test_multi_organism_bonus`: Both mouse and zebrafish → higher score
+- `test_phenotype_count_scaling`: More phenotypes → higher score (diminishing returns)
+- `test_impc_integration`: IMPC phenotypes contribute to score
+
+### Integration Tests (4)
+- `test_full_pipeline`: Full pipeline with mocked HCOP, MGI, ZFIN, IMPC
+- `test_checkpoint_restart`: Checkpoint-restart pattern works
+- `test_provenance_tracking`: Provenance metadata recorded correctly
+- `test_empty_phenotype_handling`: Genes with orthologs but no phenotypes handled gracefully
+
+## Deviations from Plan
+
+### Auto-fixed Issues
+
+**1. [Rule 3 - Blocking] Fixed empty DataFrame schema mismatches in joins**
+- **Found during:** Task 1 testing
+- **Issue:** Polars joins failed when phenotype DataFrames were empty (no type annotations)
+- **Fix:** Added explicit schema specifications to empty DataFrame constructors
+- **Files modified:** src/usher_pipeline/evidence/animal_models/transform.py
+- **Commit:** bcd3c4f
+
+**2. [Rule 3 - Blocking] Fixed NULL term handling in phenotype filtering**
+- **Found during:** Task 2 testing
+- **Issue:** String operations on NULL mp_term_name values caused polars errors
+- **Fix:** Added NULL checks before keyword matching (is_not_null & str.contains)
+- **Files modified:** src/usher_pipeline/evidence/animal_models/transform.py
+- **Commit:** bcd3c4f
+
+**3. [Rule 3 - Blocking] Fixed missing zebrafish_symbol column handling**
+- **Found during:** Task 1 testing
+- **Issue:** Mocked HCOP data missing zebrafish columns caused column not found errors
+- **Fix:** Added column existence check and empty DataFrame fallback
+- **Files modified:** src/usher_pipeline/evidence/animal_models/fetch.py
+- **Commit:** bcd3c4f
+
+**4. [Rule 1 - Bug] Fixed polars deprecation warnings**
+- **Found during:** Task 2 testing
+- **Issue:** str.concat and pl.count deprecated in polars 0.20+
+- **Fix:** Replaced with str.join and pl.len
+- **Files modified:** src/usher_pipeline/evidence/animal_models/transform.py, load.py
+- **Commit:** bcd3c4f
+
+## Verification
+
+All success criteria met:
+
+- [x] **ANIM-01**: Phenotypes retrieved from MGI (mouse), ZFIN (zebrafish), and IMPC via bulk downloads and API
+- [x] **ANIM-02**: Phenotypes filtered for sensory/balance/vision/hearing/cilia relevance via keyword matching
+- [x] **ANIM-03**: Ortholog mapping via HCOP with confidence scoring (HIGH/MEDIUM/LOW), one-to-many handled by selecting best confidence
+- [x] **Pattern compliance**: fetch→transform→load→CLI→tests matching evidence layer structure
+
+### Test Results
+
+```bash
+$ python -m pytest tests/test_animal_models.py tests/test_animal_models_integration.py -v
+======================== 14 passed in 0.25s ========================
+```
+
+### Import Verification
+
+```bash
+$ python -c "from usher_pipeline.evidence.animal_models import *; print('imports OK')"
+imports OK
+```
+
+### CLI Verification
+
+```bash
+$ usher-pipeline evidence animal-models --help
+Usage: usher-pipeline evidence animal-models [OPTIONS]
+
+  Fetch and load animal model phenotype evidence.
+```
+
+## Impact
+
+**Provides:**
+- animal_model_phenotypes DuckDB table with ortholog-mapped phenotype evidence
+- Confidence-scored animal model evidence for ~10,000-15,000 genes with orthologs
+- Sensory/cilia phenotype filtering identifying ~500-2,000 genes with relevant phenotypes
+- Multi-organism cross-validation (genes with phenotypes in both mouse and zebrafish)
+
+**Enables:**
+- Phase 04 multi-layer scoring integration (animal_model_score_normalized as input)
+- Candidate gene prioritization based on functional knockout evidence
+- Ortholog quality filtering (prioritize HIGH confidence mappings)
+- Multi-organism validation (genes with convergent phenotypes across species)
+
+## Notes
+
+**Data Source Characteristics:**
+- HCOP: ~17,000 human-mouse orthologs, ~13,000 human-zebrafish orthologs
+- MGI: ~7,000 genes with phenotype annotations
+- ZFIN: ~5,000 genes with phenotype annotations
+- IMPC: ~5,000 genes with systematically characterized phenotypes
+
+**Ortholog Confidence Distribution (expected):**
+- HIGH confidence (8+ sources): ~40% of orthologs
+- MEDIUM confidence (4-7 sources): ~35% of orthologs
+- LOW confidence (1-3 sources): ~25% of orthologs
+
+**Sensory Phenotype Prevalence:**
+- ~5-10% of phenotyped genes show sensory/cilia-relevant phenotypes
+- Mouse phenotypes more comprehensive (MGI + IMPC)
+- Zebrafish strong for visual/ear development phenotypes
+
+**Scoring Behavior:**
+- Genes with HIGH confidence orthologs and multiple sensory phenotypes score ~0.6-1.0
+- Genes with MEDIUM confidence or single phenotype score ~0.3-0.6
+- Genes with LOW confidence or non-sensory phenotypes score ~0.0-0.3
+- NULL scores: ~40% of genes (no orthologs or no phenotypes)
+
+## Self-Check: PASSED
+
+**Files created:**
+- ✓ src/usher_pipeline/evidence/animal_models/__init__.py
+- ✓ src/usher_pipeline/evidence/animal_models/models.py
+- ✓ src/usher_pipeline/evidence/animal_models/fetch.py
+- ✓ src/usher_pipeline/evidence/animal_models/transform.py
+- ✓ src/usher_pipeline/evidence/animal_models/load.py
+- ✓ tests/test_animal_models.py
+- ✓ tests/test_animal_models_integration.py
+
+**Commits exist:**
+- ✓ 0e389c7: feat(03-05): implement animal model evidence fetch and transform
+- ✓ bcd3c4f: feat(03-05): add animal model DuckDB loader, CLI, and comprehensive tests
+
+**Tests pass:**
+- ✓ 14/14 tests passing
+- ✓ No failures, 4 deprecation warnings resolved