DEEPGEN^TM-A Novel Variant Calling Assay for Low Frequency Variants

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Next-generation sequencing (NGS) enables precision oncology by detecting genetic variants.
• Low-frequency variants in liquid biopsies are critical for early cancer detection and treatment but are often obscured by background noise.
• Current variant calling assays face limitations in accuracy for detecting rare variants.

Purpose of the Study:

• To develop and validate DEEPGEN™, a novel variant calling assay for sensitive detection of low-frequency genetic variants in liquid biopsy samples.
• To assess the performance and minimal input requirements of DEEPGEN™ for clinical applications.

Main Methods:

• Targeted, short-read sequencing with high depth was employed.
• Reference samples with validated mutations at known low frequencies (0%-0.5%) were processed.
• DEEPGEN™ performance was evaluated against a commercial liquid biopsy assay.

Main Results:

• DEEPGEN™ demonstrated effectiveness in discriminating true variants from background noise down to 0.09% variant allele frequency.
• The assay achieved a limit of detection (LOD(90)) at 0.18% variant allele frequency.
• Orthogonal comparison confirmed superior sensitivity of DEEPGEN™ compared to a commercial assay.

Conclusions:

• DEEPGEN™ offers a sensitive and accurate method for detecting low-frequency genetic variants in liquid biopsies.
• The assay has significant potential for improving early cancer detection and personalized treatment strategies.
• DEEPGEN™ overcomes limitations of existing assays in managing background noise for rare variant detection.