Abstract 418: Highly efficient duplex DNA tagging strategy improves accuracy of detecting ultra-low-frequency mutations through consensus read reconstruction

Introduction: Molecular diagnostics and precise personalized care continue to increase the sensitivity and specificity requirements for detecting low (~5%) to ultra-low ( 4,000 false positives, resulting in a positive predictive value (PPV) of 90% detection sensitivity was achieved for genomic and cell-free DNA samples with 0 false positives, resulting in 100% PPV, a >40-fold error suppression. For FFPE DNA samples, the duplex adapters provided >30-fold PPV improvement compared to standard adapters. Conclusions: The duplex UMI adapters eliminate background NGS errors by collapsing duplicated reads using their unique tags. This leads to unprecedented accuracy in detecting true low-frequency variants, regardless of the input DNA source. Such advances are key to refining diagnostics and improving precision cancer care. Citation Format: Jiashi Wang, Kevin Lai, Madelyn Light, Layla Katiraee, Kristina Giorda, Mirna Jarosz, Yun Bao, Criss Walworth, David Kupec, Caifu Chen. Highly efficient duplex DNA tagging strategy improves accuracy of detecting ultra-low-frequency mutations through consensus read reconstruction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 418.