DEEPGENTM—A Novel Variant Calling Assay for Low Frequency Variants

Genes

Johannes Bhakdi¹  Sebastian Pfeil¹  Samuel Schaible¹  Robert Kunze¹  BerndTimo Hermann¹  Nicole Groenke¹  MonikaElisabeth Hagen²  Frédéric Ris² 

[1] Department of Research & Development, Quantgene Inc. 2940 Nebraska Ave, Santa Monica, CA 90404, USA;Department of Surgery, University Hospital Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva, Switzerland;

关键词: variant calling;    performance validation;    liquid biopsy;    NGS;    precision medicine;    early cancer detection;   

DOI  :  10.3390/genes12040507

来源: DOAJ

【 摘 要 】

Detection of genetic variants in clinically relevant genomic hot-spot regions has become a promising application of next-generation sequencing technology in precision oncology. Effective personalized diagnostics requires the detection of variants with often very low frequencies. This can be achieved by targeted, short-read sequencing that provides high sequencing depths. However, rare genetic variants can contain crucial information for early cancer detection and subsequent treatment success, an inevitable level of background noise usually limits the accuracy of low frequency variant calling assays. To address this challenge, we developed DEEPGEN^TM, a variant calling assay intended for the detection of low frequency variants within liquid biopsy samples. We processed reference samples with validated mutations of known frequencies (0%–0.5%) to determine DEEPGEN^TM’s performance and minimal input requirements. Our findings confirm DEEPGEN^TM’s effectiveness in discriminating between signal and noise down to 0.09% variant allele frequency and an LOD(90) at 0.18%. A superior sensitivity was also confirmed by orthogonal comparison to a commercially available liquid biopsy-based assay for cancer detection.

【 授权许可】

Unknown