Multi-cancer early detection using cell-free DNA methylome analysis

项目总结 及早发现癌症是抗击癌症的最好方法。多发癌的早期进展 检测(MCed)液体活组织检查为将早期癌症检测纳入常规检测提供了巨大的希望 临床护理。然而，目前的MCED测试在早期癌症方面的表现并不令人满意。 最近，我们开发了一种灵敏而经济的技术，称为无细胞DNA甲基组 测序(cfMethyl-Seq)，它使用无细胞DNA甲基组进行早期癌症检测。Cf甲基-序列号 在CpG岛上提供12倍于全基因组亚硫酸盐测序的丰富。我们做了证明- 在结肠癌、肝癌、肺癌和胃癌患者队列中应用cfMethyl-seq的原理研究 在检测和定位这些癌症类型方面取得了令人振奋的结果。在这里，我们将进一步 改进cfMethyl-seq技术并将其应用于结肠癌、胃癌、肝癌和肺癌的检测和定位。我们 将在多个临床队列中验证这种MCed测试。我们的多学科团队提出了以下目标： (1)继续改进用于早期癌症检测的cfMethyl-seq试验。(二)持续改善 我们的计算方法来分析cfDNA甲基组分析数据。(3)cfDNA的临床验证 甲基组分析是以结肠癌/胃癌/肝癌/肺癌为首发指征的MCed法。(四)贡献力量 合作跨联盟活动。我们与行业合作伙伴有着长期的合作关系， 早期诊断，它将优化cfMethyl-seq检测，以促进其临床应用，并实施 在一个安全的云计算平台上计算算法，方便数据共享和分散测试。

PROJECT SUMMARY Detecting cancer early is the best way to fight against cancer. The development of the Multi-Cancer Early Detection (MCED) liquid biopsy tests holds great promise for integrating early cancer detection into routine clinical care. However, the current MCED tests have unsatisfactory performance for early-stage cancers. Recently, we have developed a sensitive and cost-effective technology, named cell-free DNA Methylome Sequencing (cfMethyl-Seq), which uses the cell-free DNA methylome for early cancer detection. cfMethyl-Seq provides >12-fold enrichment over whole genome bisulfite sequencing in CpG islands. We performed the proof- of-principle study by applying cfMethyl-seq to a cohort of colon, liver, lung, and stomach cancer patients and controls, and obtained promising results in detecting and locating these cancer types. Here, we will further improve the cfMethyl-seq technology and apply it to detect and locate colon, gastric, liver, and lung cancer. We will validate this MCED test in multiple clinical cohorts. Our multidisciplinary team proposes the following aims: (1) Continued improvement of the cfMethyl-seq assay for early cancer detection. (2) Continued improvement of our computational method to analyze the cfDNA methylome assay data. (3) Clinically validate the cfDNA Methylome assay as an MCED assay with colon/gastric/liver/lung cancers as the first indications. (4) Contribute to Collaborative Trans-consortium Activities. We have a long-standing collaboration with the industry partner, EarlyDiagnostics, which will optimize the cfMethyl-seq assay to facilitate its clinical adoption and implement the computational algorithm in a secure cloud computing platform to facilitate data sharing and decentralized testing.