Cell-free DNA TAPS provides multimodal information for early cancer detection.

Cell-free DNA TAPS provides multimodal information for early cancer detection.
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DOI:
10.1126/sciadv.abh0534
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发表时间:
2021-09-03
期刊:
影响因子:
13.6
通讯作者:
Song CX
Song CX
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Siejka-Zielińska P;Cheng J;Jackson F;Liu Y;Soonawalla Z;Reddy S;Silva M;Puta L;McCain MV;Culver EL;Bekkali N;Schuster-Böckler B;Palamara PF;Mann D;Reeves H;Barnes E;Sivakumar S;Song CX

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新的无细胞DNA全基因组甲基组测序方法使准确的癌症检测。循环无细胞DNA (cfDNA)中表观遗传和遗传信息的多模式全基因组表征可以实现更敏感的早期癌症检测,但在技术上具有挑战性。最近,我们开发了tet辅助吡啶硼烷测序(TAPS),这是一种温和的,无亚硫酸盐的碱基分辨率直接DNA甲基化测序方法。在这里,我们优化了cfDNA的TAPS (cfTAPS),以提供高质量和高深度的全基因组无细胞甲基组。我们将cfTAPS应用于85份来自肝细胞癌(HCC)或胰腺导管腺癌(PDAC)患者和非癌症对照的cfDNA样本。仅从10 ng cfDNA(1至3 ml血浆)中,我们就生成了迄今为止最全面的cfDNA甲基组。我们证明了cfTAPS提供了关于cfDNA特征的多模式信息,包括DNA甲基化,起源组织和DNA片段化。综合分析这些表观遗传学和遗传学特征可以准确识别早期HCC和PDAC。
Novel cell-free DNA whole-genome methylome sequencing method enables accurate cancer detection. 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.
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