"""Tests for NegBioDB GE (Gene Essentiality) database layer. Tests migration, connection, table creation, and pair aggregation. """ import sqlite3 import tempfile from pathlib import Path import pytest from negbiodb_depmap.depmap_db import ( create_ge_database, get_connection, refresh_all_ge_pairs, run_ge_migrations, ) MIGRATIONS_DIR = Path(__file__).parent.parent / "migrations_depmap" @pytest.fixture def tmp_db(tmp_path): """Create a temporary GE database with all migrations applied.""" db_path = tmp_path / "test_ge.db" run_ge_migrations(db_path, MIGRATIONS_DIR) return db_path @pytest.fixture def conn(tmp_db): """Get a connection to the temporary GE database.""" c = get_connection(tmp_db) yield c c.close() # ── Migration tests ─────────────────────────────────────────────────── class TestMigrations: def test_migration_creates_all_tables(self, conn): """All 10 expected tables should exist after migration.""" tables = { row[0] for row in conn.execute( "SELECT name FROM sqlite_master WHERE type='table'" ).fetchall() } expected = { "schema_migrations", "dataset_versions", "genes", "cell_lines", "ge_screens", "ge_negative_results", "gene_cell_pairs", "ge_split_definitions", "ge_split_assignments", "prism_compounds", "prism_sensitivity", } assert expected.issubset(tables), f"Missing tables: {expected - tables}" def test_migration_version_recorded(self, conn): """Migration 001 should be recorded in schema_migrations.""" versions = { row[0] for row in conn.execute( "SELECT version FROM schema_migrations" ).fetchall() } assert "001" in versions def test_migration_idempotent(self, tmp_db): """Running migrations twice should not fail or duplicate.""" applied = run_ge_migrations(tmp_db, MIGRATIONS_DIR) assert applied == [], "No new migrations expected on second run" def test_create_ge_database(self, tmp_path): """create_ge_database convenience wrapper should work.""" db_path = tmp_path / "convenience.db" result = create_ge_database(db_path, MIGRATIONS_DIR) assert result == db_path assert db_path.exists() # ── Connection tests ────────────────────────────────────────────────── class TestConnection: def test_wal_mode(self, conn): mode = conn.execute("PRAGMA journal_mode").fetchone()[0] assert mode == "wal" def test_foreign_keys_enabled(self, conn): fk = conn.execute("PRAGMA foreign_keys").fetchone()[0] assert fk == 1 # ── Schema constraint tests ────────────────────────────────────────── class TestSchemaConstraints: def test_gene_entrez_unique(self, conn): """Entrez ID should be unique.""" conn.execute( "INSERT INTO genes (entrez_id, gene_symbol) VALUES (7157, 'TP53')" ) conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( "INSERT INTO genes (entrez_id, gene_symbol) VALUES (7157, 'TP53_DUP')" ) def test_cell_line_model_id_unique(self, conn): """Model ID should be unique.""" conn.execute( "INSERT INTO cell_lines (model_id, ccle_name) VALUES ('ACH-000001', 'A549_LUNG')" ) conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( "INSERT INTO cell_lines (model_id, ccle_name) VALUES ('ACH-000001', 'DUP')" ) def test_confidence_tier_check(self, conn): """Invalid confidence tier should fail.""" conn.execute("INSERT INTO genes (entrez_id, gene_symbol) VALUES (1, 'A')") conn.execute("INSERT INTO cell_lines (model_id) VALUES ('ACH-000001')") conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 1, 'crispr_nonessential', 'platinum', 'depmap', 'test', 'score_threshold')""" ) def test_evidence_type_check(self, conn): """Invalid evidence type should fail.""" conn.execute("INSERT INTO genes (entrez_id, gene_symbol) VALUES (1, 'A')") conn.execute("INSERT INTO cell_lines (model_id) VALUES ('ACH-000001')") conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 1, 'invalid_type', 'bronze', 'depmap', 'test', 'score_threshold')""" ) def test_screen_type_check(self, conn): """Screen type must be crispr or rnai.""" with pytest.raises(sqlite3.IntegrityError): conn.execute( """INSERT INTO ge_screens (source_db, depmap_release, screen_type) VALUES ('depmap', '25Q3', 'sirna')""" ) def test_negative_result_dedup(self, conn): """Duplicate gene-cell_line-screen-source should be rejected.""" conn.execute("INSERT INTO genes (entrez_id, gene_symbol) VALUES (1, 'A')") conn.execute("INSERT INTO cell_lines (model_id) VALUES ('ACH-000001')") conn.execute( """INSERT INTO ge_screens (source_db, depmap_release, screen_type) VALUES ('depmap', '25Q3', 'crispr')""" ) conn.commit() conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, screen_id, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 1, 1, 'crispr_nonessential', 'bronze', 'depmap', 'r1', 'score_threshold')""" ) conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, screen_id, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 1, 1, 'crispr_nonessential', 'bronze', 'depmap', 'r2', 'score_threshold')""" ) def test_prism_broad_id_unique(self, conn): """PRISM broad_id should be unique.""" conn.execute( "INSERT INTO prism_compounds (broad_id, name) VALUES ('BRD-K001', 'Drug1')" ) conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( "INSERT INTO prism_compounds (broad_id, name) VALUES ('BRD-K001', 'Drug2')" ) def test_foreign_key_gene(self, conn): """FK from ge_negative_results to genes should be enforced.""" conn.execute("INSERT INTO cell_lines (model_id) VALUES ('ACH-000001')") conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (999, 1, 'crispr_nonessential', 'bronze', 'depmap', 'test', 'score_threshold')""" ) def test_foreign_key_cell_line(self, conn): """FK from ge_negative_results to cell_lines should be enforced.""" conn.execute("INSERT INTO genes (entrez_id, gene_symbol) VALUES (1, 'A')") conn.commit() with pytest.raises(sqlite3.IntegrityError): conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 999, 'crispr_nonessential', 'bronze', 'depmap', 'test', 'score_threshold')""" ) # ── Pair aggregation tests ──────────────────────────────────────────── def _insert_test_data(conn): """Insert synthetic test data for pair aggregation tests.""" # 3 genes, 2 cell lines conn.execute("INSERT INTO genes (gene_id, entrez_id, gene_symbol) VALUES (1, 7157, 'TP53')") conn.execute("INSERT INTO genes (gene_id, entrez_id, gene_symbol) VALUES (2, 673, 'BRAF')") conn.execute("INSERT INTO genes (gene_id, entrez_id, gene_symbol) VALUES (3, 2064, 'ERBB2')") conn.execute("INSERT INTO cell_lines (cell_line_id, model_id) VALUES (1, 'ACH-000001')") conn.execute("INSERT INTO cell_lines (cell_line_id, model_id) VALUES (2, 'ACH-000002')") # Screen conn.execute( """INSERT INTO ge_screens (screen_id, source_db, depmap_release, screen_type, algorithm) VALUES (1, 'depmap', '25Q3', 'crispr', 'Chronos')""" ) conn.execute( """INSERT INTO ge_screens (screen_id, source_db, depmap_release, screen_type, algorithm) VALUES (2, 'demeter2', 'DEMETER2_v6', 'rnai', 'DEMETER2')""" ) # Gene 1 (TP53) non-essential in both cell lines (CRISPR) conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, screen_id, gene_effect_score, dependency_probability, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 1, 1, 0.05, 0.1, 'crispr_nonessential', 'gold', 'depmap', 'r1', 'score_threshold')""" ) conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, screen_id, gene_effect_score, dependency_probability, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 2, 1, 0.02, 0.15, 'crispr_nonessential', 'silver', 'depmap', 'r2', 'score_threshold')""" ) # Gene 1 (TP53) also non-essential in cell line 1 via RNAi conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, screen_id, gene_effect_score, dependency_probability, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (1, 1, 2, 0.08, NULL, 'rnai_nonessential', 'bronze', 'demeter2', 'r3', 'score_threshold')""" ) # Gene 2 (BRAF) non-essential in cell line 1 only conn.execute( """INSERT INTO ge_negative_results (gene_id, cell_line_id, screen_id, gene_effect_score, dependency_probability, evidence_type, confidence_tier, source_db, source_record_id, extraction_method) VALUES (2, 1, 1, -0.3, 0.35, 'crispr_nonessential', 'bronze', 'depmap', 'r4', 'score_threshold')""" ) conn.commit() class TestPairAggregation: def test_refresh_pair_count(self, conn): """Should create correct number of aggregated pairs.""" _insert_test_data(conn) count = refresh_all_ge_pairs(conn) conn.commit() # Gene 1 in cell line 1 (2 sources), Gene 1 in cell line 2 (1 source), # Gene 2 in cell line 1 (1 source) = 3 pairs assert count == 3 def test_multi_source_pair(self, conn): """Pair with CRISPR + RNAi should have num_sources=2.""" _insert_test_data(conn) refresh_all_ge_pairs(conn) conn.commit() row = conn.execute( """SELECT num_screens, num_sources, best_confidence, min_gene_effect, max_gene_effect FROM gene_cell_pairs WHERE gene_id = 1 AND cell_line_id = 1""" ).fetchone() assert row is not None assert row[0] == 2 # num_screens assert row[1] == 2 # num_sources (depmap + demeter2) assert row[2] == "gold" # best_confidence assert row[3] == pytest.approx(0.05) # min_gene_effect assert row[4] == pytest.approx(0.08) # max_gene_effect def test_single_source_pair(self, conn): """Pair with single source should have num_sources=1.""" _insert_test_data(conn) refresh_all_ge_pairs(conn) conn.commit() row = conn.execute( """SELECT num_screens, num_sources, best_confidence FROM gene_cell_pairs WHERE gene_id = 2 AND cell_line_id = 1""" ).fetchone() assert row is not None assert row[0] == 1 # num_screens assert row[1] == 1 # num_sources assert row[2] == "bronze" def test_gene_degree(self, conn): """Gene 1 should have degree 2 (non-essential in 2 cell lines).""" _insert_test_data(conn) refresh_all_ge_pairs(conn) conn.commit() row = conn.execute( "SELECT gene_degree FROM gene_cell_pairs WHERE gene_id = 1 LIMIT 1" ).fetchone() assert row[0] == 2 def test_cell_line_degree(self, conn): """Cell line 1 should have degree 2 (2 genes non-essential).""" _insert_test_data(conn) refresh_all_ge_pairs(conn) conn.commit() row = conn.execute( "SELECT cell_line_degree FROM gene_cell_pairs WHERE cell_line_id = 1 LIMIT 1" ).fetchone() assert row[0] == 2 def test_mean_gene_effect(self, conn): """Mean gene effect should be computed correctly.""" _insert_test_data(conn) refresh_all_ge_pairs(conn) conn.commit() row = conn.execute( """SELECT mean_gene_effect FROM gene_cell_pairs WHERE gene_id = 1 AND cell_line_id = 1""" ).fetchone() # Average of 0.05 (CRISPR) and 0.08 (RNAi) = 0.065 assert row[0] == pytest.approx(0.065) def test_refresh_clears_old_pairs(self, conn): """Refreshing should delete old pairs and split assignments.""" _insert_test_data(conn) refresh_all_ge_pairs(conn) conn.commit() # Add a split assignment conn.execute( """INSERT INTO ge_split_definitions (split_name, split_strategy) VALUES ('test_split', 'random')""" ) pair_id = conn.execute("SELECT pair_id FROM gene_cell_pairs LIMIT 1").fetchone()[0] conn.execute( """INSERT INTO ge_split_assignments (pair_id, split_id, fold) VALUES (?, 1, 'train')""", (pair_id,), ) conn.commit() # Refresh again count = refresh_all_ge_pairs(conn) conn.commit() assert count == 3 # Split assignments should be cleared sa_count = conn.execute( "SELECT COUNT(*) FROM ge_split_assignments" ).fetchone()[0] assert sa_count == 0 def test_empty_results(self, conn): """Refreshing with no results should produce 0 pairs.""" count = refresh_all_ge_pairs(conn) assert count == 0 # ── Index tests ─────────────────────────────────────────────────────── class TestIndices: def test_key_indices_exist(self, conn): """Critical indices should exist for query performance.""" indices = { row[1] for row in conn.execute("PRAGMA index_list('ge_negative_results')").fetchall() } assert "idx_ge_nr_gene" in indices assert "idx_ge_nr_cell_line" in indices assert "idx_ge_nr_pair" in indices assert "idx_ge_nr_tier" in indices assert "idx_ge_nr_unique_source" in indices def test_cell_line_indices(self, conn): """Cell line lookup indices should exist.""" indices = { row[1] for row in conn.execute("PRAGMA index_list('cell_lines')").fetchall() } assert "idx_cell_lines_ccle" in indices assert "idx_cell_lines_stripped" in indices def test_prism_indices(self, conn): """PRISM bridge indices should exist.""" indices = { row[1] for row in conn.execute("PRAGMA index_list('prism_compounds')").fetchall() } assert "idx_prism_inchikey" in indices assert "idx_prism_chembl" in indices