WHOLE GENOME SEQUENCING FOR SOMATIC MUTATIONS IN GTEX

Broad将为TOPMed提供代谢组学和蛋白质组学服务。 代谢组学。 代谢组学技术提供了人血浆和组织样本的系统生化表征。我们已经建立了一个高通量代谢组学平台， 基于真实标准品测量了600多种已知代谢物，以及我们正在有条不紊地表征的数千个LC-MS峰。我们的方法整合了 靶向和非靶向LC-MS方法。我们严格处理了试验内和试验间的变异性，以“群体”水平规模采集数据。在FHS、糖尿病预防研究、妇女健康倡议和其他队列的先前分析中，我们已经确定了心脏代谢疾病的新生物标志物，并在模型系统中整合了遗传信息和研究，以确定新的生物学途径。为了响应2017年发布的关于2000个梅萨样本的试点代谢组学研究和2018年发布的关于约8000个样本的CORE第3年代谢物分析的任务订单请求，我们提供了完整及时的高质量靶向和非靶向数据，在两种情况下都满足了最后期限。我们目前正在与梅萨研究人员合作，为CORE第4年的数据生成生成约8000份血浆样本的代谢组学数据。自试点研究以来，我们一直积极响应TOPM研究人员的代谢组学数据工作，并支持和合作进行数据分析。 基于这些经验，我们寻求提供代谢组学能力，以响应任务订单请求（TORFP）#75N92020R0034;集中组学资源（CORE）;任务领域5：使用我们的高通量，多学科方法的代谢物谱。

The Broad will provide both metabolomics and proteomics service for the TOPMed. Metabolomics. Metabolomic technologies provide the systematic biochemical characterization of human plasma and tissue samples. We have established a high-throughput metabolomics platform that measures over 600 known metabolites based on authentic standards, as well as thousands of LC-MS peaks that we are methodically working to characterize. Our methods integrate both targeted and non-targeted LC-MS approaches. We have rigorously addressed intra- and interassay variability, acquiring data at “population” level scale. In prior analyses in the Framingham Heart Study (FHS), the Diabetes Prevention Study, the Women’s Health Initiative and other cohorts, we have identified novel biomarkers of cardiometabolic disease and integrated genetic information and studies in model systems to identify novel biologic pathways. In response to Task Order Request for Proposals issued in 2017 for pilot metabolomics studies on 2000 MESA samples and in 2018 for CORE Year 3 metabolite profiling of approximately 8000 samples, we provided high quality targeted and nontargeted data delivered in a complete and timely manner, meeting deadlines in both cases. We are presently collaborating with MESA investigators to generate metabolomics data on approximately 8000 plasma samples for Data generation for CORE Year 4. Since the pilot studies, we have been responsive to TOPMed investigators working with metabolomics data and have supported and collaborated on data analysis. Based on these experiences, we seek to provide metabolomic capabilities in response to Task Order Request for Proposal (TORFP) #75N92020R0034; Centralized Omics REsource (CORE); Task Area 5: Metabolite Profiles using our high throughput, multidisciplinary approach.