Aperture

Aperture identifies structural variations (SVs) and viral integrations in circulating tumor DNA (ctDNA) using an alignment-free approach to detect low-frequency and complex junctions.

Key Features:

• Alignment-Free Strategy: Employs an alignment-free approach that leverages k-mer-based searching to identify SVs without relying on traditional sequence alignment.
• Breakpoint Detection: Utilizes binary labels to detect breakpoints and clusters candidate regions to identify SVs that span repetitive genomic regions.
• Barcode-Based Filtering: Incorporates a barcode-based filter to distinguish true SV events from sequencing artifacts and noise.
• High Sensitivity and Specificity: Demonstrates improved sensitivity and specificity relative to existing methods across stimulated, reference, and real patient datasets, notably in low dilution tests.
• Viral Integration Prediction: Predicts sites of viral integration in ctDNA.
• Complex SV Identification: Identifies complex SVs involving novel insertions and repetitive sequences.

Scientific Applications:

• ctDNA-based Precision Oncology: Enables sensitive and specific detection of SVs and viral integrations in ctDNA to enhance diagnostic interpretation in precision oncology.
• Treatment Selection and Monitoring: Provides genomic alteration information from ctDNA to support clinician decision-making for treatment selection and disease monitoring in personalized cancer care.

Methodology:

Processes paired-end reads in FASTQ format using alignment-free k-mer-based searching, applies binary-label breakpoint detection with clustering of candidate regions and barcode-based filtering, and outputs detected SVs and viral integrations in VCF 4.2 format.