CNVfilteR

CNVfilteR filters false-positive germline copy-number variant (CNV) calls by leveraging single-nucleotide variant (SNV) calls from germline NGS pipelines, implemented as an R/Bioconductor package to improve CNV detection accuracy.

Key Features:

• Implementation: Implemented as an R package within the Bioconductor framework.
• SNV integration: Uses single-nucleotide variant (SNV) calls obtained during germline NGS pipelines to assess CNV calls.
• False deletion and duplication detection: Identifies false deletions and false duplications within CNV callsets.
• Compatibility with multiple callers: Applies to CNV callsets generated by a variety of CNV calling tools.
• Performance gains: Demonstrated reductions in false positives up to 44.8% and consistent improvements in F1-score.
• Evaluation scope: Tested on callsets from 13 CNV calling tools across three whole-genome sequencing projects and 541 panel samples.
• Pipeline integration: Designed to be applied within existing CNV calling pipelines to refine results.

Scientific Applications:

• Hereditary disease studies: Refines germline CNV calls used in studies of hereditary diseases.
• Variant interpretation: Reduces false positives to improve interpretation of CNVs in genetic analyses.
• CNV-caller benchmarking: Supports evaluation and comparison of CNV calling tool performance.

Methodology:

Integrates SNV calls from germline NGS pipelines with CNV callsets to identify and flag false deletions and duplications; implemented as an R/Bioconductor package.