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 #
5R01ES022190-03
Application #
8687655
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
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$433,176
Indirect Cost
$224,816
Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352
Khadempour, Lily; Burnum-Johnson, Kristin E; Baker, Erin S et al. (2016) The fungal cultivar of leaf-cutter ants produces specific enzymes in response to different plant substrates. Mol Ecol 25:5795-5805
Kyle, Jennifer E; Zhang, Xing; Weitz, Karl K et al. (2016) Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry. Analyst 141:1649-59
Liu, Rui; Chen, Shuang; Cheng, Shuang et al. (2016) Surprising impact of remote groups on the folding--unfolding and dimer-chain equilibria of bifunctional H-bonding unimers. Chem Commun (Camb) 52:3773-6
Cong, Yongzheng; Katipamula, Shanta; Trader, Cameron D et al. (2016) Mass spectrometry-based monitoring of millisecond protein-ligand binding dynamics using an automated microfluidic platform. Lab Chip 16:1544-8
Burnum-Johnson, Kristin E; Nie, Song; Casey, Cameron P et al. (2016) Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry. Mol Cell Proteomics 15:3694-3705
Zhang, Xing; Ibrahim, Yehia M; Chen, Tsung-Chi et al. (2015) Enhancing biological analyses with three dimensional field asymmetric ion mobility, low field drift tube ion mobility and mass spectrometry (μFAIMS/IMS-MS) separations. Analyst 140:6955-63
Baker, Erin Shammel; Burnum-Johnson, Kristin E; Ibrahim, Yehia M et al. (2015) Enhancing bottom-up and top-down proteomic measurements with ion mobility separations. Proteomics 15:2766-76
Cha, Jeeyeon; Burnum-Johnson, Kristin E; Bartos, Amanda et al. (2015) Muscle Segment Homeobox Genes Direct Embryonic Diapause by Limiting Inflammation in the Uterus. J Biol Chem 290:15337-49
Ibrahim, Yehia M; Baker, Erin S; Danielson 3rd, William F et al. (2015) Development of a New Ion Mobility (Quadrupole) Time-of-Flight Mass Spectrometer. Int J Mass Spectrom 377:655-662
Baker, Erin Shammel; Burnum-Johnson, Kristin E; Jacobs, Jon M et al. (2014) Advancing the high throughput identification of liver fibrosis protein signatures using multiplexed ion mobility spectrometry. Mol Cell Proteomics 13:1119-27

Showing the most recent 10 out of 14 publications