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， 基于血液的甲基化特征测试，可以及早发现和定位癌症。临床 对癌症早期进行干预可以极大地提高癌症存活率 病人。尽管在临床实践中对早期检测方法的需求很大，但很少有 技术在市场上是存在的。为了解决这一未得到满足的需求，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 而且还推断出它的位置(起源组织)。为了增加这一功能的力量 计算框架，同一个加州大学洛杉矶分校团队和EarlyDx团队最近开发了 一种新的实验方法--无细胞DNA还原表示亚硫酸盐 测序(CfRRBS)，有效地丰富覆盖甲基化的cfDNA片段 血样中的地点。将这两项创新结合起来，可以产生一种具有高灵敏度和 早期肝癌患者的特异性。这项测试现已准备好用于临床。 使用。拟议的项目将把这些原则证明实验室方案转化为 商业级检测，并验证其在肝癌检测中的有效性。 该项目为第一阶段可行性研究。我们的具体目标如下： 目的1)开发早期Dx4甲基扫描分析的商业原型 和成本有效的全基因组甲基化分析；目的2)验证 早期Dx4甲基扫描试验检测肝癌经过工程处理的样品 在目标1中将使用片段DNA以确保分析的重复性 在开发过程中。CancerDetector算法已经在我们的 云计算平台。利用这一平台，新的化验将被用于进行癌症 对100名真实的肝癌患者和100名对照的队列进行预测。第一阶段将是 成功论证了肝癌早期检测的可行性。第二阶段 (以及更多)将进一步将该测试应用于多种类型的癌症，并最终实现商业化 测试：首先作为实验室的研究产品，最后作为临床产品 医院。

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.