An Accurate, Non-invasive, and Cost-effective Methylome Test for Early Cancer Detection

该项目的长期目标是开发和销售一种商业上可行的， 基于血液的甲基化分析测试，可以早期检测和定位癌症。临床 在癌症的早期阶段进行干预可以大大提高癌症的生存率 患者尽管在临床实践中对早期检测方法有巨大的需求，但很少有 市场上有技术。为了解决这一未满足的需求，在NIH的支持下，我们的 加州大学洛杉矶分校的合作伙伴的团队已经开发出一种基于全基因组甲基化分析的方法， 无细胞DNA（cfDNA）。他们的新技术名为CancerDetector，不仅可以早期发现癌症， 而且还推断其位置（起源组织）。为了增加它的能量 计算框架，同一UCLA团队与EarlyDx团队最近开发了 一种新的实验方法，称为无细胞DNA还原表示亚硫酸氢盐 测序（cfRRBS），有效富集覆盖甲基化的cfDNA片段 血液样本中的位点。结合这两种创新产生了具有高灵敏度的测试， 早期肝癌患者的特异性。该测试现已准备好适应临床 使用.拟议的项目将把这些原理验证实验室协议转化为 商业级测定，并验证其用于检测肝癌的有效性。 该项目为一期可行性研究。我们的具体目标如下： 目的1）开发EarlyDx 4 MethylScan测定的商业原型，用于准确的 和具有成本效益的全基因组甲基化分析;目的2） 用于检测肝癌的EarlyDx 4 MethylScan测定。工程样品 目的1中将使用片段化DNA，以确保试验的重现性 在发展过程中。CancerDetector算法已经在我们的 云计算平台。利用这个平台，新的检测方法将用于进行癌症 在100名真实的肝癌患者和100名对照者的队列中进行预测。第一阶段将是 通过成功证明肝癌早期检测的可行性完成。二期 (and beyond）将进一步将该测试应用于多种类型的癌症，并最终商业化 测试：首先作为实验室的研究产品，最后作为临床产品， 医院的

The long-term goal of this project is to develop and market a commercially viable, blood-based methylation profiling test that can detect and locate cancer early. Clinical intervention in the early stages of cancer can greatly improve the survival of cancer patients. Despite the tremendous demand for early detection methods in the clinical practice, few technologies exist on the market. To address this unmet need, with support from the NIH, our partner’s team at UCLA has developed an approach based on the genome-wide methylation analysis of cell-free DNA (cfDNA). Their novel technology, called CancerDetector, not only detects cancer early but also infers its location (tissue of origin). To increase the power of this computational framework, the same UCLA team together with EarlyDx team recently developed a novel experimental approach, called cell-free DNA Reduced Representation Bisulfite Sequencing (cfRRBS), that efficiently enriches the cfDNA fragments covering methylation sites in a blood sample. Combining the two innovations yields a test with high sensitivity and specificity in early-stage liver cancer patients. This test is now ready to be adapted for clinical use. The proposed project will translate these proof-of-principle laboratory protocols into a commercial-grade assay, and validate its effectiveness for the detection of liver cancer. This project is for a Phase I feasibility study. Our specific aims are as follows: Aim 1) Develop a commercial prototype of the EarlyDx4MethylScan assay for accurate and cost4effective genome4wide methylation profiling; Aim 2) Validate the EarlyDx4MethylScan assay for the detection of liver cancer. Engineered samples of fragmented DNAs will be used in Aim 1 to ensure the reproducibility of the assay during development. The CancerDetector algorithm has already been implemented in our cloud-computing platform. Using this platform, the new assay will be used to perform cancer prediction in a cohort of 100 real liver cancer patients and 100 controls. Phase I will be completed by successfully demonstrating the feasibility of liver cancer early detection. Phase II (and beyond) will further apply the test to multiple types of cancer, and eventually commercialize the test: first as a research product for labs, and finally as a clinical product ready for hospitals.