gbanyan
174c4af02d
- Implement filter_by_coverage with quality_flag categorization (measured/incomplete_coverage/no_data) - Add normalize_scores with LOEUF inversion (lower LOEUF = higher score) - NULL preservation throughout pipeline (unknown != zero constraint) - process_gnomad_constraint end-to-end pipeline function - 15 comprehensive unit tests covering edge cases: - NULL handling and preservation - Coverage filtering without dropping genes - Normalization bounds and inversion - Mixed type handling for robust parsing - Fix column mapping to handle gnomAD v4.x loeuf/loeuf_upper duplication - All existing tests continue to pass
62 lines
2.6 KiB
Python
62 lines
2.6 KiB
Python
"""Data models for gnomAD constraint metrics."""
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from pydantic import BaseModel
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# gnomAD v4.1 constraint metrics download URL
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GNOMAD_CONSTRAINT_URL = (
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"https://storage.googleapis.com/gcp-public-data--gnomad/release/4.1/constraint/"
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"gnomad.v4.1.constraint_metrics.tsv"
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)
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# Column name mapping for different gnomAD versions
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# v2.1.1 uses: gene, transcript, pLI, oe_lof_upper (LOEUF upper CI), mean_proportion_covered_bases
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# v4.x uses: gene, transcript, mane_select, lof.pLI, lof.oe_ci.upper (LOEUF), mean_proportion_covered
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# NOTE: In gnomAD data, what's called "upper" is actually the LOEUF value we want (observed/expected upper bound)
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COLUMN_VARIANTS = {
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"gene_id": ["gene", "gene_id"],
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"gene_symbol": ["gene_symbol", "gene"],
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"transcript": ["transcript", "canonical_transcript", "mane_select"],
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"pli": ["pLI", "lof.pLI", "pli"],
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# LOEUF is the "upper" column in gnomAD (oe_lof_upper = observed/expected upper bound)
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"loeuf": ["lof.oe_ci.upper", "oe_lof_upper", "oe_lof", "loeuf"],
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# loeuf_upper is typically the same as loeuf in gnomAD data (they report the upper CI)
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"loeuf_upper": ["lof.oe_ci.upper", "oe_lof_upper_ci", "oe_lof_upper"],
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"mean_depth": ["mean_coverage", "mean_depth", "mean_cov"],
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"cds_covered_pct": [
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"mean_proportion_covered_bases",
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"mean_proportion_covered",
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"cds_covered_pct",
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],
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}
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class ConstraintRecord(BaseModel):
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"""gnomAD constraint metrics for a single gene.
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Attributes:
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gene_id: Ensembl gene ID (e.g., ENSG00000...)
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gene_symbol: HGNC gene symbol
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transcript: Canonical transcript ID
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pli: Probability of being loss-of-function intolerant (NULL if no estimate)
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loeuf: Loss-of-function observed/expected upper bound fraction (NULL if no estimate)
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loeuf_upper: Upper bound of LOEUF confidence interval
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mean_depth: Mean exome sequencing depth across CDS
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cds_covered_pct: Fraction of CDS bases with adequate coverage (0.0-1.0)
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quality_flag: Data quality indicator - "measured", "incomplete_coverage", or "no_data"
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loeuf_normalized: Normalized LOEUF score (0-1, inverted: higher = more constrained)
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CRITICAL: NULL values represent missing data and are preserved as None.
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Do NOT convert NULL to 0.0 - "unknown" is semantically different from "zero constraint".
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"""
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gene_id: str
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gene_symbol: str
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transcript: str
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pli: float | None = None
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loeuf: float | None = None
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loeuf_upper: float | None = None
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mean_depth: float | None = None
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cds_covered_pct: float | None = None
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quality_flag: str = "no_data"
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loeuf_normalized: float | None = None
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