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: 9066675
• 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 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9066675
• 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; 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; informatics infrastructure; instrument; ion mobility; ion source; ionization; mass spectrometer; metabolome; 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）：本项目的总体目标是开发并初步评价一种新型的基于多维离子迁移率-质谱的高通量代谢组学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，其将提供以下测量：与目前的平台相比，更加稳健、提供更大的覆盖范围和灵敏度、超过一个数量级的更高的通量，并且具有更高的定量效用。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接口的新发展。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，以有效地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品集进行比较，并且在许多情况下，其他检测到的物质也基于其准确的质量、MS/MS数据和结构相关的离子迁移率信息进行鉴定，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，以使该技术更广泛地提供。

项目成果

PIXiE: an algorithm for automated ion mobility arrival time extraction and collision cross section calculation using global data association.

• DOI: 10.1093/bioinformatics/btx305
• 发表时间: 2017-09-01
• 期刊: Bioinformatics (Oxford, England)
• 作者: Ma J;Casey CP;Zheng X;Ibrahim YM;Wilkins CS;Renslow RS;Thomas DG;Payne SH;Monroe ME;Smith RD;Teeguarden JG;Baker ES;Metz TO
• 通讯作者: Metz TO

The fungal cultivar of leaf-cutter ants produces specific enzymes in response to different plant substrates.

切叶蚁的真菌品种会针对不同的植物基质产生特定的酶。

• DOI: 10.1111/mec.13872
• 发表时间: 2016-11
• 期刊: Molecular ecology
• 影响因子: 4.9
• 作者: Khadempour L;Burnum-Johnson KE;Baker ES;Nicora CD;Webb-Robertson BM;White RA 3rd;Monroe ME;Huang EL;Smith RD;Currie CR
• 通讯作者: Currie CR

Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches.

• DOI: 10.1016/j.cbpa.2017.11.009
• 发表时间: 2018-03
• 期刊: Current opinion in chemical biology
• 影响因子: 7.8
• 作者: Zheng X;Smith RD;Baker ES
• 通讯作者: Baker ES

Online Ozonolysis Combined with Ion Mobility-Mass Spectrometry Provides a New Platform for Lipid Isomer Analyses.

在线臭氧分解与离子淌度质谱联用为脂质异构体分析提供了新平台。

• DOI: 10.1021/acs.analchem.7b04091
• 发表时间: 2018-01-16
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Poad BLJ;Zheng X;Mitchell TW;Smith RD;Baker ES;Blanksby SJ
• 通讯作者: Blanksby SJ