This funding request is for an Orbitrap Elite/H-ESI Mass Spectrometer Bundle to support NIH-sponsored projects involving clinical biomarker development, disease prediction and classification and therapeutic development for personalized medicine. New analytic workflow developed by the PI in collaboration with investigators in the Departments of Medicine, Chemistry, Biostatistics and Bioinformatics and Environmental Health at Emory University has provided capability to routinely and reproducibly measure >20,000 high- resolution m/z features in extracts of human plasma and other biological materials. Many of these m/z features are significantly associated with specific diseases, but most are of low abundance, and over half do not match chemicals in human metabolic databases. Verification of identities and characterization of unidentified chemicals are challenging yet critical to the goals of major users with NIH grants in basic, translational and clinical research. The requested instrument will be used to apply specialized deconvolution MS/MS methods to confirm identities of significant, low abundance chemicals in these projects, and to characterize unidentified chemicals with predicted MS/MS spectra suitable for chemical database entry and searches. Strategies have been developed within the Department of Medicine (DOM) Clinical Biomarkers Laboratory, in conjunction with the Emory Mass Spectrometry Center, to use deconvolution MS/MS to create predicted MS/MS spectra, and MSn, to aid in identification of these significant, low-abundance chemicals present in complex mixtures such as human plasma. The requested instrument is specifically justified by the capability to accumulate and dissociate low-abundance ions and measure product ions with sufficient mass accuracy and resolution to gain insight into elemental composition and structure. The instrument will be maintained and operated by skilled personnel in the DOM Clinical Biomarkers Laboratory with specific training in high-resolution mass spectrometry and computational biology, biostatistics and bioinformatics. Major and minor users will provide a standard fee for service by skilled technicians within the DOM Clinical Biomarkers Laboratory. The instrument purchase will be cost-shared by the DOM Clinical Biomarkers Laboratory and operated within this laboratory with priority given to the named major users and a group of minor users also supported by NIH grants. Excess capacity will be used with priority given to other NIH-sponsored research, pilot and feasibility projects for NIH grant submissions, and other sponsored projects according to policies established by a High-Resolution Metabolomics Advisory Committee. The instrument will be maintained by the DOM Clinical Biomarkers Laboratory with a service contract and a cost recovery system to assure long-term operation and maintenance.

Public Health Relevance

This high-resolution mass spectrometry system will be used to support NIH-sponsored projects involving biomarker development, disease prediction and classification and therapeutic development for personalized medicine. Specific use is to verify identities and aid in identification of low abundance chemicals associated with disease. Advanced computational methods will be used to deconvolute ion dissociation spectra and provide predicted MS/MS and MSn spectra of low abundance m/z features.

National Institute of Health (NIH)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1)
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Birken, Steven
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Emory University
Internal Medicine/Medicine
Schools of Medicine
United States
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