Platform Providing Increased Throughput, Sensitivity and Specificity for Metabolo

为代谢提供更高通量、灵敏度和特异性的平台

• 批准号: 8857441
• 负责人: Erin S Baker
• 金额: $ 43.32万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8857441
• 关键词: Automobile Driving; Bioinformatics; Biological; Blood; Cataloging; Catalogs; Characteristics; Chemicals; Complex; Data; Data Quality; Data Set; Databases; Detection; Development; Diabetes Mellitus; Disease; Environment; Florida; Gases; Growth; Health Sciences; Industry; Informatics; Ions; Laboratories; Letters; Mass Spectrum Analysis; Measurement; Measures; Oregon; Output; Parents; Pathway interactions; Patients; Performance; Phase; Process; Research; Research Infrastructure; Resolution; Sampling; Sensitivity and Specificity; Serum; Software Tools; Spectrometry; Speed; Spottings; Staging; Technology; Time; Tube; Universities; base; biological systems; clinically relevant; computerized data processing; data acquisition; diabetic; improved; instrument; ion mobility; ion source; ionization; mass spectrometer; metabolomics; nano-electrospray; novel; older men; statistics; tool

DESCRIPTION (provided by applicant): The overall objective of this project is to develop and initially evaluate a novel multidimensional ion mobility- mass spectrometry based high throughput metabolomics platform and associated automated informatics pipeline for analyses of biomedically and clinically relevant samples that will provide measurements that will be: much more robust, provide greater coverage and sensitivity, be more than an order of magnitude higher throughput, and have higher quantitative utility compared to present platforms. The new platform will exploit new developments in ionization, ion funnel technology, multidimensional ion mobility separations, and mass spectrometry interfacing. Improvements to the speed of the bioinformatics pipeline will be achieved in part by creating accurate mass and time (AMT) tag databases that utilize information from the multidimensional ion mobility separations in conjunction with accurate mass information to effectively identify previously cataloged metabolites and enable broad quantitative comparisons for different samples. The initially unknown metabolites observed in these measurements can also be compared across sample sets, and in many cases other detected species also identified based on their accurate masses, MS/MS data, and structurally related ion mobility information, and thus driving a continued expansion of the metabolite AMT tag database. The new platform and informatics pipeline will be initially evaluated and demonstrated using significant sets of blood spot and serum samples, and rapidly disseminated to make the technology more broadly available.

描述（由申请人提供）：该项目的总体目标是开发并初步评估一种基于高通量代谢组学平台的新型多维离子淌度-质谱分析平台和相关的自动化信息学管道，用于分析生物医学和临床相关样本，该管道将提供以下测量结果：更加稳健，提供更大的覆盖范围和灵敏度，吞吐量提高一个数量级以上，并且具有更高的定量性 与现有平台相比的实用性。新平台将利用电离、离子漏斗技术、多维离子淌度分离和质谱接口方面的新发展。生物信息学流程速度的提高将部分通过创建精确质量和时间 (AMT) 标签数据库来实现，该数据库利用多维离子淌度分离的信息与精确质量信息相结合，有效识别先前编目的代谢物，并能够对不同样品进行广泛的定量比较。在这些测量中观察到的最初未知的代谢物也可以跨样本集进行比较，并且在许多情况下，其他检测到的物种也可以根据其精确质量、MS/MS 数据和结构相关的离子淌度信息进行识别，从而推动代谢物 AMT 标签数据库的持续扩展。新平台和信息学管道将使用大量血斑和血清样本进行初步评估和演示，并迅速传播以使该技术得到更广泛的应用。