Development of a semi-targeted lipidomic method for clinical applicationsTools Liu, Ke (2023) Development of a semi-targeted lipidomic method for clinical applications. PhD thesis, University of Nottingham.
AbstractLipids are a diverse and ubiquitous group of biomolecules incorporating more than 180,000 different molecular species. In general, lipids are considered amphipathic or hydrophobic small molecules that are produced partially or entirely by carbocation/carbanion-based condensations of isoprene/thioester units, respectively. To fill the gap between untargeted lipidomics and targeted lipidomics, a ‘semi-targeted’ lipidomics method is proposed to monitor the concentration fold change of hundreds of lipids in the human body. A semi-targeted approach will explore the relationship between different classes of lipids and potential pathways of certain diseases, as well as the relative change of each lipid at the same time. However, this method is to some extent ambiguous as the lack of reliable lipid identification can limit the analytical confidence in the profiling data. To overcome this problem, it was decided to use a comprehensive and confirmed list of lipids in human plasma that have been quantified in a widely accepted definitive published paper and build up an unambiguous lipid database. The plan is to optimise the method by comparing the extraction method, mobile phase proportion, gradient, running time and different columns. Therefore, a pre-defined list of lipids with known formula, exact mass and the fold change of these lipids was analysed to study specific diseases in order to monitor disease onset and progress and to identify diagnostic lipid biomarkers. These biomarkers can be used as new targets for chemotherapy and the development of new drugs.
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