(Georgia Institute of Technology, 2021-01-19)
Huang, Danning
Mass Spectrometry (MS) is the most commonly used technology in metabolomics studies. The high sensitivity of MS enables the detection of low abundance metabolites that are below the detection threshold of other analytical platforms, and high resolution greatly reduces spectral overlaps. When coupled with separation techniques, such as ultra- performance liquid chromatography (UPLC), spectral complexity is greatly reduced and metabolic chemical properties can be revealed. Overall, MS-based non-targeted metabolomics allows the detection and identification of a wide range of metabolites with high sensitivity and high resolution.
In this thesis work, UPLC-MS based non-targeted metabolomics was used to investigate metabolic alterations and discover potential biomarkers for high-grade serous carcinoma (HGSC) and medulloblastoma (MB). The evaluation of two leading analytical platforms, Orbitrap ID-X and 12T solariX FT-ICR mass spectrometers, in mass accuracy and relative isotope abundance (RIA) measurements of 13C1 and 18O1, and how these affect the assignment of the correct elemental formulae was performed. In addition, a multi-omics approach was performed to discover candidate critical quality attributes (CQA) that are predictive of MSC immunomodulatory capacity.
Taken together, this thesis work has contributed meaningfully to the metabolomics field by discovering potential biomarkers for HGSC and MB diseases, providing the first comparison between high- resolution FT-ICR-MS and Orbitrap Tribrid MS platforms for elemental formulae annotation purposes. Furthermore, the thesis work also provides candidate CQAs that are predictive of MSC immunomodulatory capacity, bringing the potential to inform future manufacturing strategies. This multi-omics approach to CQA discovery can also be translated into other cell therapies.