BRACNAC

BRACNAC detects copy number variations (CNVs) and copy number alterations (CNAs) in BRCA1 and BRCA2 from next-generation sequencing (NGS) data for diagnostic assessment of patient eligibility for targeted therapies.

Key Features:

• Targeted Detection: Analyzes CNVs/CNAs specifically within BRCA1 and BRCA2 genes.
• Versatile Data Compatibility: Processes NGS data from in-house and commercial library preparation kits and is compatible with whole-exome sequencing (WES) and targeted NGS datasets.
• Coverage Normalization and CNV Probability Evaluation: Employs multiple coverage normalization steps followed by CNV probability evaluation.
• Performance Metrics: Demonstrates sensitivity of 100%, specificity of 94%, and area under the curve (AUC) of 94% on reported datasets.
• External Data Performance: Achieved AUC up to 99.9% when tested on publicly available WES and targeted NGS datasets.
• Validation: Validated on NGS data from 213 ovarian and prostate cancer samples with multiplex ligation-dependent probe amplification (MLPA) results from 12 CNV-positive samples.
• Operational Constraints: Requires a minimum of 20 samples per NGS run and at least 80% CNV-negative samples within the dataset.

Scientific Applications:

• Clinical diagnostics: Identification of BRCA1/2 CNVs to inform assessment of patient eligibility for targeted therapies in ovarian and prostate cancers.
• Research studies: Comparative analysis of BRCA1/2 copy number status across WES and targeted NGS datasets.
• Clinical validation workflows: Application in diagnostic workflows validated against MLPA results for CNV-positive samples.

Methodology:

Performs multiple coverage normalization steps on NGS-derived coverage data followed by CNV probability evaluation.