SCARD

SCARD detects and characterizes rare genomic structural variants using an integrated approach with split-read, chimeric read-pair, and read-depth difference signals from genome sequencing data.

Key Features:

• Rare SV Detection: Detects rare structural variants with minor allele frequency <1% using split-read, chimeric read-pair, and read-depth difference signals.
• SV Characterization: Precisely delineates structural variant composition, including deletions, duplications, and genomic rearrangements.
• Exon-affecting SV Identification: Identifies rare SVs affecting exons with high specificity.
• De novo SV Detection: Detects de novo structural variants in trio and proband sequencing data.
• Validation against Long-read Sequencing: Achieves 97.9% specificity for all SVs, 98.0% for deletions/duplications, and 94% for structural rearrangements when validated against long-read sequencing datasets.

Scientific Applications:

• Recessive Disease Research: Investigates the role of rare structural variants in autosomal recessive conditions and their carrier rates in human populations.
• Population-scale SV Spectrum Analysis: Characterizes the spectrum of rare structural variants across thousands of genomes from population sequencing projects such as the 1000 Genomes Project.
• Clinical Variant Interpretation: Enables correct interpretation of clinically significant structural variants that are missed or misinterpreted by other methods.
• Trio-based De novo Mutation Studies: Quantifies de novo structural variant rates in probands and trios for understanding spontaneous genomic rearrangements.

Methodology:

SCARD integrates split-read, chimeric read-pair, and read-depth difference signals. The method was validated using long-read sequencing datasets and compared against 13 other callers.