I-Corps: Epigenetic Profiling of DNA Methylation: Detection & Diagnostics

I-Corps：DNA 甲基化的表观遗传分析：检测

• 批准号: 1355306
• 负责人: Adam Marsh
• 金额: $ 5万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1355306&HistoricalAwards=false
• 关键词: Corps; Epigenetic; Profiling; DNA; Methylation

Researchers are using a diagnostic technology to pursue linkages between shifts in gene expression patterns mediated by epigenetic DNA modifications and the early onset of a disease etiology. The eventual result is that molecular, biochemical and physiological activities will diverge from a normative state and overtly express the disease symptom progression. If shifts in gene expression could be detected early, a diagnosis could be made before symptoms were significant. Better yet, detecting pre-symptomatic changes in regulatory controls over gene expression events (like epigenetic DNA methylation) would make it possible to diagnosis the pre-onset of an impending disease or disease risk. Early intervention prior to the onset of any disease could potentially reduce the progression of the disease and perhaps reduce the severity of the symptoms. The team proposes to apply an epigenetic profiling technology to the characterization of human lung cancer tumors. Once a tumor is large enough to spot on an x-ray it usually has already metastasized to nearby lymph nodes. Consequently, there is a large unmet need for tests that can diagnose certain types of cancer at an early stage, when the cancer is more likely to respond to treatment. The team is pursuing technical proof of concept work for the epigenetic profiling platform. The team's quantitative algorithms are combined with statistical pattern recognition technology that can enable rapid and cost-effective screening of billions of base pairs of sequence data in a biopsy or tissue sample, producing a sophisticated and statistically rigorous report to an attending physician, clinic or submitting laboratory. This information can be critical for the development of effective personalized medicine strategies for a broad range of disease detection and treatment needs. With genome sequencing rapidly becoming cost-effective, there is an increasing requirement for profiling DNA methylation sites within a patient's genome to provide an individual fingerprint profile of abnormal gene activities. This project may solve this need for rapid, high-throughput, low-cost, computational modeling and statistical pattern recognition to identify how a patient's DNA methylation profile varies from a normative population state.

研究人员正在使用一种诊断技术来研究由表观遗传DNA修饰介导的基因表达模式的变化与疾病病因的早期发作之间的联系。最终的结果是，分子、生化和生理活动将偏离正常状态，并公开表达疾病症状进展。如果基因表达的变化可以早期发现，就可以在症状明显之前做出诊断。更好的是，检测对基因表达事件（如表观遗传DNA甲基化）的调节控制中的症状前变化将使诊断即将发生的疾病或疾病风险的发病前成为可能。在任何疾病发作之前进行早期干预可能会减少疾病的进展，并可能减轻症状的严重程度。该团队建议将表观遗传分析技术应用于人类肺癌肿瘤的表征。 一旦肿瘤大到足以在X射线上发现，它通常已经转移到附近的淋巴结。因此，对于可以在早期阶段诊断某些类型的癌症的测试存在大量未满足的需求，此时癌症更有可能对治疗做出反应。该团队正在为表观遗传分析平台进行概念工作的技术验证。该团队的定量算法与统计模式识别技术相结合，可以快速且具有成本效益地筛选活检或组织样本中数十亿个碱基对的序列数据，为主治医生，诊所或提交实验室提供复杂且统计严格的报告。这些信息对于开发有效的个性化医疗策略以满足广泛的疾病检测和治疗需求至关重要。随着基因组测序迅速变得具有成本效益，越来越需要对患者基因组内的DNA甲基化位点进行分析，以提供异常基因活性的个体指纹图谱。该项目可以解决快速，高通量，低成本，计算建模和统计模式识别的需求，以确定患者的DNA甲基化谱如何与正常人群状态不同。