# Project State ## Project Reference See: .planning/PROJECT.md (updated 2026-02-11) **Core value:** Produce a high-confidence, multi-evidence-backed ranked list of under-studied cilia/Usher candidate genes that is fully traceable — every gene's inclusion is explainable by specific evidence, and every gap is documented. **Current focus:** Phase 2 complete — ready for Phase 3 ## Current Position Phase: 3 of 6 (Core Evidence Layers) Plan: 4 of 6 in current phase Status: In progress — 03-04 complete (subcellular localization) Last activity: 2026-02-11 — Completed 03-04-PLAN.md (Subcellular Localization evidence layer) Progress: [█████░░░░░] 40.0% (8/20 plans complete across all phases) ## Performance Metrics **Velocity:** - Total plans completed: 8 - Average duration: 4.7 min - Total execution time: 0.63 hours **By Phase:** | Phase | Plans | Total | Avg/Plan | |-------|-------|-------|----------| | 01 - Data Infrastructure | 4/4 | 14 min | 3.5 min/plan | | 02 - Prototype Evidence Layer | 2/2 | 8 min | 4.0 min/plan | | 03 - Core Evidence Layers | 2/6 | 16 min | 8.0 min/plan | | Phase 03 P05 | 10 | 2 tasks | 8 files | ## Accumulated Context ### Decisions Decisions are logged in PROJECT.md Key Decisions table. Recent decisions affecting current work: - Python over R/Bioconductor for rich data integration ecosystem - Weighted rule-based scoring over ML for explainability - Public data only for reproducibility - Modular CLI scripts for flexibility during development - Virtual environment required for dependency isolation (01-01: PEP 668 externally-managed Python) - Auto-creation of directories on config load (01-01: data_dir, cache_dir field validators) - [01-02]: Warn on gene count outside 19k-22k range but don't fail (allows for Ensembl version variations) - [01-02]: HGNC success rate is primary validation gate (UniProt mapping tracked but not used for pass/fail) - [01-02]: Take first UniProt accession when multiple exist (simplifies data model) - [01-02]: Mock mygene in tests (avoids rate limits, ensures reproducibility) - [01-03]: DuckDB over SQLite for DataFrame storage (native polars/pandas integration, better analytics) - [01-03]: Provenance sidecar files alongside outputs (co-located metadata, bioinformatics standard pattern) - [01-04]: Click for CLI framework (standard Python CLI library with excellent UX) - [01-04]: Setup command uses checkpoint-restart pattern (gene universe fetch can take minutes) - [01-04]: Mock mygene in integration tests (avoids external API dependency, reproducible) - [02-01]: httpx over requests for streaming downloads (async-native, cleaner API) - [02-01]: structlog for structured logging (JSON-formatted, context-aware) - [02-01]: LOEUF normalization with inversion (lower LOEUF = more constrained = higher 0-1 score) - [02-01]: Quality flags instead of filtering (preserve all genes with measured/incomplete_coverage/no_data categorization) - [02-01]: NULL preservation pattern (unknown constraint != zero constraint, must not be conflated) - [02-01]: Lazy polars evaluation (LazyFrame until final collect() for query optimization) - [02-02]: load_to_duckdb uses CREATE OR REPLACE for idempotency (safe to re-run) - [02-02]: CLI evidence command group for extensibility (future evidence sources follow same pattern) - [02-02]: Checkpoint at table level (has_checkpoint checks DuckDB table existence) - [02-02]: Integration tests with synthetic fixtures (no external downloads, fast, reproducible) - [03-01]: Annotation tier thresholds: Well >= (20 GO AND 4 UniProt), Partial >= (5 GO OR 3 UniProt) - [03-01]: Composite annotation score weighting: GO 50%, UniProt 30%, Pathway 20% - [03-01]: NULL GO counts treated as zero for tier classification but preserved as NULL in data (conservative assumption) - [03-04]: Evidence type terminology standardized to computational (not predicted) for consistency with bioinformatics convention - [03-04]: Proteomics absence stored as False (informative negative) vs HPA absence as NULL (unknown/not tested) - [03-04]: Curated proteomics reference gene sets (CiliaCarta, Centrosome-DB) embedded as Python constants for simpler deployment - [03-04]: Computational evidence (HPA Uncertain/Approved) downweighted to 0.6x vs experimental (Enhanced/Supported, proteomics) at 1.0x - [Phase 03-05]: Ortholog confidence based on HCOP support count (HIGH: 8+, MEDIUM: 4-7, LOW: 1-3) - [Phase 03-05]: NULL score for genes without orthologs (preserves NULL pattern) ### Pending Todos None yet. ### Blockers/Concerns None yet. ## Session Continuity Last session: 2026-02-11 - Plan execution Stopped at: Completed 03-04-PLAN.md (Subcellular Localization evidence layer) Resume file: .planning/phases/03-core-evidence-layers/03-04-SUMMARY.md