SVScore

SVScore predicts the impact of structural variants by aggregating SNP pathogenicity scores across relevant genomic intervals to assess potential deleterious effects on genomic function.

Key Features:

• Pathogenicity Score Aggregation: Aggregates SNP pathogenicity scores across genomic intervals for each structural variant to estimate combined deleterious potential.
• Consideration of Variant Characteristics: Incorporates variant type and gene features into score aggregation to refine impact estimates.
• Positional Uncertainty Handling: Accounts for positional uncertainty in SV coordinates when aggregating scores.
• Selection Pressure Insights: Reports that high-scoring SVs are enriched at lower allele frequencies, consistent with purifying selection.
• Comparison with Alternative Methods: Demonstrates improved identification of deleterious variants relative to alternative methods based on empirical comparisons.
• Duplication and Deletion Selection: Identifies that duplications may be under stronger selection pressure than deletions.
• Equivalence in Pathogenicity Potential: Finds a comparable number of strongly pathogenic SVs and SNPs within human populations.

Scientific Applications:

• Variant Prioritization: Prioritizes structural variants for experimental validation or clinical investigation by scoring deleterious potential.
• Population Genetics and Evolutionary Inference: Analyzes allele frequency distributions of high-scoring SVs to infer purifying selection and differential selection between duplications and deletions.
• Disease Association and Functional Genomics: Supports studies of SV contribution to genetic disorders and phenotypic traits by providing impact predictions.

Methodology:

Aggregates SNP pathogenicity scores across SV-overlapping genomic intervals while incorporating variant type, gene features, and positional uncertainty in the score calculation.