Slade, Susan E. (2013) Application of label-free mass spectrometry-based proteomics to biomarker discovery. PhD thesis, University of Warwick.

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Abstract

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.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General)
Library of Congress Subject Headings (LCSH):	Biochemical markers, Mass spectrometry, Proteomics
Official Date:	April 2013
Dates:	Date Event April 2013 Submitted
Institution:	University of Warwick
Theses Department:	School of Life Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Scrivens, James H.
Sponsors:	Nicolaides, K. H.; Fetal Medicine Foundation (London, U.K.)
Extent:	xx, 225 leaves : illustrations, charts.
Language:	eng

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