VPOT

VPOT prioritizes genetic variants from next-generation sequencing (NGS) data by computing customizable pathogenicity ranking scores for ANNOVAR-annotated VCFs and enabling variant filtering by candidate gene lists and pedigree affected status.

Key Features:

• Customizable pathogenicity ranking: Generates a single pathogenicity ranking score by integrating any number of annotation values with user-defined weights.
• Integration with ANNOVAR annotations: Operates on VCF files annotated with ANNOVAR.
• Efficient variant filtering: Filters variants using predefined candidate gene lists or by affected status within family pedigrees.
• Scalability and performance: Designed to handle datasets with thousands to millions of variants per sample for cohort-scale analyses.

Scientific Applications:

• Disease-causal variant identification: Prioritizes candidate disease-causal variants from NGS data for genetic disorder studies.
• Familial disease investigations: Applies pedigree-based filtering to identify variants segregating with affected status in families.
• Cohort-scale prioritization: Enables prioritization across multiple samples in cohort studies to aid pathogenic mutation discovery.

Methodology:

Implemented as a Python-based command-line application that reads ANNOVAR-annotated VCFs, computes a weighted pathogenicity score from annotation values, and applies filters based on candidate gene lists and pedigree affected status.