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

使用游离 DNA 甲基化分析进行多癌症早期检测

基本信息

批准号：
10763305
负责人：
ROBERT S BRESALIER
金额：
$ 95.26万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-19 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10763305
关键词：
Adoption Benign Biological Biological Assay Biological Markers Biopsy Blood Blood specimen Breast Bypass Cancer Detection Cancer Patient Cervix Uteri Cessation of life Clinical Cloud Computing Collaborations Colon Colon Carcinoma Colorectal Neoplasms Communication Computational algorithm Computing Methodologies Copy Number Polymorphism CpG Islands DNA DNA methylation profiling Data Decentralization Detection Development Diagnostic Disease Early Diagnosis Endoscopy Enrollment General Population Human Image Immune Incidence Individual Learning Literature Liver Lung Malignant Neoplasms Malignant neoplasm of liver Malignant neoplasm of lung Methylation Modality Modeling Names Nature Neural Network Simulation Nodule Organ Patients Performance Plasma Proteins Protocols documentation Publishing RNA Recommendation Reproducibility Resource Sharing Sampling Screening for Hepatocellular Cancer Screening for cancer Secure Signal Transduction Site Specificity Stomach Technology Testing Time Tissues Training Tube United States Validation bioinformatics tool bisulfite bisulfite sequencing cancer biomarkers cancer cell cancer diagnosis cancer type cell free DNA clinical care cohort computational platform computer framework cost cost effective data sharing deep neural network detection assay detection test exosome fighting high risk improved industry partner liquid biopsy liver cancer patient malignant stomach neoplasm methylation pattern methylome microbial multidisciplinary multiple omics prospective restriction enzyme screening screening program trial design whole genome

项目摘要

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.

项目概要及早发现癌症是对抗癌症的最佳方法。多种癌症早期的发展检测 (MCED) 液体活检测试有望将早期癌症检测纳入常规临床护理。然而，目前的 MCED 测试对于早期癌症的表现并不令人满意。最近，我们开发了一种敏感且经济高效的技术，称为无细胞DNA甲基化技术测序 (cfMmethyl-Seq)，使用游离 DNA 甲基化组进行早期癌症检测。 cf甲基测序与 CpG 岛的全基因组亚硫酸氢盐测序相比，富集度超过 12 倍。我们进行了证明—— 将 cfMmethyl-seq 应用于结肠癌、肝癌、肺癌和胃癌患者队列的原理性研究控制，并在检测和定位这些癌症类型方面获得了有希望的结果。在此，我们将进一步改进cfMmethyl-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该 MCED 测试。我们的多学科团队提出以下目标： (1) 持续改进用于早期癌症检测的 cfMmethyl-seq 检测。（二）持续改进我们分析 cfDNA 甲基化组测定数据的计算方法。 (3) cfDNA的临床验证甲基化组测定作为 MCED 测定，以结肠癌/胃癌/肝癌/肺癌作为第一个适应症。 (4) 贡献跨联盟合作活动。我们与行业合作伙伴有着长期的合作， EarlyDiagnostics，将优化 cfMmethyl-seq 检测，以促进其临床采用并实施安全云计算平台中的计算算法，以促进数据共享和分散测试。