ADDING ADDITIONAL FUNDS UNDER OPTION PERIOD 1, TASK AREAS 5 AND 6, FOR CORE YEAR 5.

在选项期 1、任务领域 5 和 6 下为核心第 5 年添加额外资金。

• 批准号: 10510183
• 负责人: ASHLIN BOLTON
• 金额: $ 1095.33万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-28 至 2022-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10510183
• 关键词: Address; Affinity; Antibodies; Area; Biochemical; Biological; Biological Assay; Biological Markers; Biological Models; Cardiometabolic Disease; Cardiovascular system; Cohort Studies; Collection; Communities; DNA; Data; Data Analyses; Diabetes prevention; Framingham Heart Study; Funding; Generations; Genetic study; Human; Institutes; Jackson Heart Study; Label; Laboratories; Mass Spectrum Analysis; Measures; Methods; National Heart, Lung, and Blood Institute; Nucleotides; Pathway interactions; Pilot Projects; Plasma; Population; Proteins; Proteomics; Protocols documentation; Request for Proposals; Research Personnel; Resources; Sampling; Services; Specificity; Technology; Time; Tissue Sample; Trans-Omics for Precision Medicine; Validation; Women' s Health; Work; aptamer; base; cohort; database of Genotypes and Phenotypes; experience; genetic information; interdisciplinary approach; meetings; metabolomics; next generation sequencing; novel; novel marker; population based; programs; response; trait

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. Proteomics Emerging proteomic technologies are beginning to permit the systematic, unbiased characterization of human plasma samples, though few data exist in large, population-based cohort studies. To address limitations of prior studies, we have established a high-throughput proteomic platform in our laboratory that measures 1,536 proteins using an extensive collection of nucleotide-labeled antibodies (Olink). The assay leverages a novel method referred to as a proximity extension assay (PEA) which can be quantified by Next Generation Sequencing (NGS). We have rigorously addressed intra- and inter-assay variability (both <13%) and acquired data >20-fold faster than mass spectrometry based methods with a level of specificity that appears to be better than existing high throughput affinity-based methods that use DNA aptamers. In new work in the Jackson Heart Study and other cohorts, we confirmed established relationships between known biomarkers and cardiovascular traits and discovered many new associations. Based on these experiences, we seek to provide proteomic capabilities in response to Task Order Request for Proposal (TORFP) #75N92020R0034; Centralized Omics REsource (CORE); Task Area 6: Proteomics using our high throughput, multidisciplinary approach. Our proposal reflects a longstanding collaborative effort between our laboratory and the Broad Institute. The present application will also couple discovery with novel “orthogonal” validation protocols using mass spectrometry. All of the data generated on our platform will be available for TOPMed investigators and will be made broadly available in real time to the scientific community via dbGap, as we have done previously. We believe this body of experience strongly. supports our plan to analyze ~8,000 samples and provide proteomic profiles as part of the NHLBI TOPMed program in the coming year.

Broad将为TOPMed提供代谢组学和蛋白质组学服务。