WHOLE GENOME SEQUENCING FOR SOMATIC MUTATIONS IN GTEX

博德将为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体血浆和组织样本的系统生化特征。我们已经建立了一个高通量的代谢组学平台 根据可靠的标准测量600多种已知代谢物，以及我们正在有条不紊地工作的数千个LC-MS峰。我们的方法将两者结合在一起 定向和非定向LC-MS方法。我们已经严格地处理了化验内和化验间的可变性，获取了“总体”水平的数据。在弗雷明翰心脏研究(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性疾病的新生物标记物，并整合了遗传信息和模型系统中的研究，以确定新的生物途径。针对2017年发布的关于2000个MESA样本的代谢组学试点研究的建议和2018年针对大约8000个样本的第3年核心代谢物分析的建议的任务单请求，我们提供了高质量的、有针对性的和非有针对性的数据，以完整和及时的方式提供，在这两种情况下都满足了最后期限。我们目前正在与MESA研究人员合作，在大约8000个血浆样本上生成代谢组学数据，以用于核心年份的数据生成。自试点研究以来，我们一直响应TOPMed研究人员处理代谢组学数据的工作，并在数据分析方面提供支持和合作。基于这些经验，我们寻求提供代谢能力，以响应任务订单征求建议书(TORFP)#75N92020R0034；集中式OMICS资源(核心)；任务区域5：使用我们的高通量、多学科方法的代谢物概况。

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.