Platform Providing Increased Throughput, Sensitivity and Specificity for Metabolo

描述(由申请人提供)：该项目的总体目标是开发和初步评估一种新的基于多维离子迁移率-质谱仪的高通量代谢组学平台和相关的自动化信息学管道，用于生物医学和临床相关样本的分析，将提供以下测量：与现有平台相比，更加可靠，提供更大的覆盖范围和灵敏度，超过一个数量级的吞吐量，并具有更高的定量实用价值。新平台将利用电离、离子漏斗技术、多维离子迁移率分离和质谱学接口方面的新发展。生物信息学管道速度的提高将部分通过创建准确的质量和时间(AMT)标签数据库来实现，该数据库利用来自多维离子迁移率分离的信息以及准确的质量信息来有效地识别先前编目的代谢物，并能够对不同的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在样本集之间进行比较，在许多情况下，还可以根据它们的准确质量、MS/MS数据和结构相关的离子迁移率信息来识别其他被检测物种，从而推动代谢物AMT标签数据库的持续扩展。新的平台和信息学管道将使用重要的血斑和血清样本进行初步评估和演示，并迅速传播，以使技术更广泛地可用。

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.