FindSV

FindSV detects and annotates structural variants from whole-genome sequencing (WGS) data to support genetic diagnosis by identifying copy-number variants, complex rearrangements, uniparental disomy (UPD), and short tandem repeat (STR) expansions.

Key Features:

• Variant Calling: Uses TIDDIT and CNVnator to call a wide range of structural variants, including large chromosomal rearrangements and small deletions/duplications.
• Variant Merging: Merges similar variants to streamline downstream analysis.
• Output Files: Generates unfiltered per-caller VCFs, a combined unfiltered VCF (_Combined.vcf), an annotated and filtered VCF (_FindSV.vcf), and a chromosome-specific ploidy tab file.
• Annotation: Annotates and filters variants using VEP, frequency databases, genmod, and custom scripts.
• Detection Scope: Supports detection of complex SVs such as ring chromosomes and insertional translocations, and identification of UPD and STR expansions.

Scientific Applications:

• Diagnostic Yield Enhancement: Increases diagnostic yield in monogenic WGS cohorts by detecting pathogenic SNVs and SVs that were missed by chromosomal microarray analysis (CMA).
• Complex Variant Detection: Identifies complex structural variants including ring chromosomes, insertional translocations, and cases of uniparental disomy such as Prader-Willi syndrome.
• Comprehensive Genetic Testing: Enables integrated analysis of SNVs, SVs, UPD, and STR expansions within a single WGS framework and provides positional information across cohorts.

Methodology:

FindSV performs variant calling with TIDDIT and CNVnator, merges similar variants, generates per-caller and combined VCFs plus a ploidy tab, and annotates/filters variants using VEP, frequency databases, genmod, and custom scripts; it was validated on a retrospective cohort with known CNVs.