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Title: Application of label-free mass spectrometry-based proteomics to biomarker discovery
Author: Slade, Susan E.
ISNI:       0000 0004 2749 5517
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2013
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Mass spectrometry is an analytical technique which is used extensively in the fields of chemistry and physics. Developments in the field over the last two decades have permitted the analysis of a wide variety of biological molecules from a range of sources. The term proteomics relates to the study of the protein complement of a cell or organism with particular interest in the identification and quantification of these analytes. A biomarker is a characteristic that can be measured and evaluated to give an indication of normal, biological processes, or pharmacological responses to a therapeutic intervention. Bodily fluids are a rich source of potential biomarkers as they can be obtained in reasonable quantity and their extraction is generally minimally invasive. The plasma proteome, which contains many thousands of analytes spanning a dynamic range greater than 10 orders of magnitude, reflects the status of the many tissues and organs in the body serving as an ideal medium for potential biomarker discovery. The analytical challenges posed by the plasma proteome are significant. Depletion of the highly abundant proteins is usually a prerequisite of any biomarker study and no technique has the dynamic range to study all of the proteins present. Comprehensive characterisation of the plasma proteome requires significant experimental effort and cost. Use of pooled samples in biomarker studies is widespread and the majority of biomarkers, which have been identified in the discovery phase, have not passed clinical validation. A data independent, label-free quantitative approach has been evaluated for the study of depleted maternal plasma proteomes taken in the first trimester. Plasma was characterised from individual and groups of patients from three obstetric conditions using single and multi-dimensional chromatography. Potential biomarkers from each source were identified and evaluated. Multi-dimensional chromatography was used to simplify the complexity of the analytes introduced to the mass spectrometer and the benefits and limitations of the approach in terms of biomarker discovery have been demonstrated.
Supervisor: Not available Sponsor: Nicolaides, K.H. ; Fetal Medicine Foundation (London, U.K.)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology ; R Medicine (General)