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.

Public Health Relevance

Metabolomics aims to provide a comprehensive approach to measure the functional output of biological pathways within biological systems that indicate characteristics of a disease, growth conditions, or other perturbations. The planned research will develop, evaluate, and initially demonstrate a new instrumental platform and associated automated informatics pipeline for analyses of biomedically and clinically relevant metabolomics samples with significantly improved sensitivity, coverage, and measurement throughput.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES022190-02
Application #
8545854
Study Section
Special Emphasis Panel (ZRG1-BST-P (50))
Program Officer
Balshaw, David M
Project Start
2012-09-15
Project End
2017-05-31
Budget Start
2013-07-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$420,181
Indirect Cost
$218,073
Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352
Nagy, Gabe; Chouinard, Christopher D; Attah, Isaac K et al. (2018) Distinguishing enantiomeric amino acids with chiral cyclodextrin adducts and structures for lossless ion manipulations. Electrophoresis 39:3148-3155
Nicora, Carrie D; Burnum-Johnson, Kristin E; Nakayasu, Ernesto S et al. (2018) The MPLEx Protocol for Multi-omic Analyses of Soil Samples. J Vis Exp :
Zheng, Xueyun; Dupuis, Kevin T; Aly, Noor A et al. (2018) Utilizing ion mobility spectrometry and mass spectrometry for the analysis of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polybrominated diphenyl ethers and their metabolites. Anal Chim Acta 1037:265-273
MacLean, Brendan X; Pratt, Brian S; Egertson, Jarrett D et al. (2018) Using Skyline to Analyze Data-Containing Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry Dimensions. J Am Soc Mass Spectrom 29:2182-2188
Poad, Berwyck L J; Zheng, Xueyun; Mitchell, Todd W et al. (2018) Online Ozonolysis Combined with Ion Mobility-Mass Spectrometry Provides a New Platform for Lipid Isomer Analyses. Anal Chem 90:1292-1300
Orton, Daniel J; Tfaily, Malak M; Moore, Ronald J et al. (2018) A Customizable Flow Injection System for Automated, High Throughput, and Time Sensitive Ion Mobility Spectrometry and Mass Spectrometry Measurements. Anal Chem 90:737-744
Zheng, Xueyun; Smith, Richard D; Baker, Erin S (2018) Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches. Curr Opin Chem Biol 42:111-118
Kyle, Jennifer E; Aly, Noor; Zheng, Xueyun et al. (2018) Evaluating lipid mediator structural complexity using ion mobility spectrometry combined with mass spectrometry. Bioanalysis 10:279-289
Bilbao, Aivett; Gibbons, Bryson C; Slysz, Gordon W et al. (2018) An algorithm to correct saturated mass spectrometry ion abundances for enhanced quantitation and mass accuracy in omic studies. Int J Mass Spectrom 427:91-99
Chouinard, Christopher D; Nagy, Gabe; Webb, Ian K et al. (2018) Rapid Ion Mobility Separations of Bile Acid Isomers Using Cyclodextrin Adducts and Structures for Lossless Ion Manipulations. Anal Chem 90:11086-11091

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