Siejka-Zielińska Paulina, Cheng Jingfei, Jackson Felix, Liu Yibin, Soonawalla Zahir, Reddy Srikanth, Silva Michael, Puta Luminita, McCain Misti Vanette, Culver Emma L, Bekkali Noor, Schuster-Böckler Benjamin, Palamara Pier Francesco, Mann Derek, Reeves Helen, Barnes Eleanor, Sivakumar Shivan, Song Chun-Xiao
Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sci Adv. 2021 Sep 3;7(36):eabh0534. doi: 10.1126/sciadv.abh0534. Epub 2021 Sep 1.
Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.
对循环游离DNA（cfDNA）中的表观遗传和遗传信息进行多模态、全基因组表征，可能有助于实现更灵敏的早期癌症检测，但在技术上具有挑战性。最近，我们开发了四氢叶酸辅助吡啶硼烷测序（TAPS），这是一种温和的、无需亚硫酸氢盐的碱基分辨率直接DNA甲基化测序方法。在此，我们对cfDNA的TAPS（cfTAPS）进行了优化，以提供高质量、高深度的全基因组游离甲基化组。我们将cfTAPS应用于85份来自肝细胞癌（HCC）或胰腺导管腺癌（PDAC）患者及非癌症对照的cfDNA样本。仅从10 ng的cfDNA（1至3毫升血浆）中，我们就生成了迄今为止最全面的cfDNA甲基化组。我们证明，cfTAPS可提供有关cfDNA特征的多模态信息，包括DNA甲基化、起源组织和DNA片段化。对这些表观遗传和遗传特征的综合分析能够准确识别早期HCC和PDAC。
