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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BST-P (50))
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Balshaw, David M
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Battelle Pacific Northwest Laboratories
United States
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Zheng, Xueyun; Smith, Richard D; Baker, Erin S (2017) 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
Zheng, Xueyun; Renslow, Ryan S; Makola, Mpho M et al. (2017) Structural Elucidation of cis/trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry. J Phys Chem Lett 8:1381-1388
Metz, Thomas O; Baker, Erin S; Schymanski, Emma L et al. (2017) Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go? Bioanalysis 9:81-98
Zheng, Xueyun; Deng, Liulin; Baker, Erin S et al. (2017) Distinguishing d- and l-aspartic and isoaspartic acids in amyloid ? peptides with ultrahigh resolution ion mobility spectrometry. Chem Commun (Camb) 53:7913-7916
Ma, Jian; Casey, Cameron P; Zheng, Xueyun et al. (2017) PIXiE: an algorithm for automated ion mobility arrival time extraction and collision cross section calculation using global data association. Bioinformatics 33:2715-2722
Zheng, Xueyun; Zhang, Xing; Schocker, Nathaniel S et al. (2017) Enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses. Anal Bioanal Chem 409:467-476
Burnum-Johnson, Kristin E; Baker, Erin S; Metz, Thomas O (2017) Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging. Placenta 60 Suppl 1:S67-S72
Stow, Sarah M; Causon, Tim J; Zheng, Xueyun et al. (2017) An Interlaboratory Evaluation of Drift Tube Ion Mobility-Mass Spectrometry Collision Cross Section Measurements. Anal Chem 89:9048-9055
Zheng, Xueyun; Wojcik, Roza; Zhang, Xing et al. (2017) Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses. Annu Rev Anal Chem (Palo Alto Calif) 10:71-92
Kyle, Jennifer E; Casey, Cameron P; Stratton, Kelly G et al. (2017) Comparing identified and statistically significant lipids and polar metabolites in 15-year old serum and dried blood spot samples for longitudinal studies. Rapid Commun Mass Spectrom 31:447-456

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