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Permanent link (DOI): https://doi.org/10.7939/R3MC8RP29
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Development of Isotope Labeling Methods and Data Processing Program for Liquid Chromatography Mass Spectrometry-Based Metabolome Analysis Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
- Supervisor and department
Li, Liang (Department of Chemistry)
- Examining committee member and department
Perreault Helene (Department of Chemistry, university of Manitoba)
Campbell, Robert (Department of Chemistry)
Harrison, Jed (Department of Chemistry)
Damaraju, Sambasivarao (Department of Laboratory Medicine and Pathology)
Clive, Derrick (Department of Chemistry)
Department of Chemistry
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
Metabolomics strives to gain a comprehensive picture of the metabolites in a biological system. This emerging research field gives us an insight into the discovery of disease-related biomarkers and an understanding of metabolic flux as well as mechanisms. Liquid chromatography mass spectrometry (LC-MS) is one of the leading techniques used in metabolomics owing to its high sensitivity and capability for structure elucidation.
The main objective of my research was to develop improved LC-MS based differential isotopic labeling methods to quantify and identify metabolites in biological samples with enhanced analytical performance. First of all, an improved dansylation labeling protocol was developed for profiling amine- and phenol-containing metabolites, which can be used to more efficiently label multiple samples in metabolome analysis. Secondly, a new triplex DIL reagent: 5-diethylamino-naphthalene-1-sulfonyl chloride (DensCl), was developed to increase the sample throughput by at least two-fold, compared to the duplex dansylation labeling approach. Thirdly, a new type of isotope labeling reagent was synthesized to provide a means of chemical structure analysis based on the MS/MS fragmentation patterns generated from the labeled metabolites. Finally, a data processing software, IsoMS, was developed to quickly extract quantitative information from LC-MS data generated by the isotope labeling method.
The significance of my research work is that the methods developed can be used to analyze the metabolome with high performance, thereby increasing the application capability of metabolomics for disease biomarker discovery and biological functional studies of metabolites in systems biology.
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- Citation for previous publication
Zhou, R.; Guo, K.; Li, L. Anal. Chem. 2013, 85, 11532-9.
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