PeCanPIE

PeCanPIE annotates and prioritizes genetic variants from Variant Call Format (VCF) files to support classification of variant pathogenicity for massively parallel sequencing studies, particularly in cancer predisposition genes.

Key Features:

• Input format: Accepts Variant Call Format (VCF) files that can contain millions of variants.
• Variant types supported: Processes single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions.
• Annotation and ranking: Performs variant annotation and ranks variants by putative pathogenicity.
• ACMG decision support: Provides decision-support aligning variant classification with published American College of Medical Genetics and Genomics (ACMG) guidelines.
• Cloud-executable pipelines: Back-end pipelines can be executed on cloud platforms for integration into larger analysis workflows.
• Expert-reviewed repository: Stores expert-reviewed variant classifications within the platform.

Scientific Applications:

• Pediatric cancer variant classification: Applied in large-scale investigations involving over 4,000 pediatric cancer patients to classify variant pathogenicity in cancer predisposition genes.
• Extension to other diseases: Adaptable for analysis of non-pediatric cancers and other genetic diseases.
• Interpretation of sequencing studies: Supports interpretation of variants derived from massively parallel sequencing.

Methodology:

Accepts VCF input; processes SNVs, indels, MNVs, and complex substitutions; annotates and ranks variants by putative pathogenicity; applies decision-support aligned with ACMG guidelines; stores expert-reviewed classifications; and supports execution of back-end pipelines on cloud platforms.