Accelerating high-throughput proteomics with proteome-selective isolation chromatography (P-SLICY)

dc.contributor.authorYeung, Darien
dc.contributor.examiningcommitteeWilkins, John (Internal Medicine)
dc.contributor.examiningcommitteeTriggs-Raine, Barbara (Biochemistry and Medical Genetics)
dc.contributor.examiningcommitteeHu, Pingzhao (Biochemistry and Medical Genetics)
dc.contributor.examiningcommitteeKonermann, Lars (University of Western Ontario)
dc.contributor.supervisorKrokhin, Oleg
dc.date.accessioned2025-01-13T17:19:55Z
dc.date.available2025-01-13T17:19:55Z
dc.date.issued2025-01-03
dc.date.submitted2025-01-03T00:55:00Zen_US
dc.degree.disciplineBiochemistry and Medical Genetics
dc.degree.levelDoctor of Philosophy (Ph.D.)
dc.description.abstractProteomics is one of the most effective ways to study protein regulation including characterizing the changes in protein quantity as a result of biological perturbation. Liquid chromatography paired with tandem mass spectrometry (LC-MS/MS) is the most commonly used analytical technology in this field. After two decades of technological advancements, the quantitation of the total human proteome still precludes us. These advancements have allowed for high throughput quantitation of near tens of thousands of proteins in hours of analysis time. However, 30% of the proteome remain elusive in routine proteomic analysis. Current LC-MS/MS methods rely on increasing the number of peptides identified to yield more protein identifications. But it has been shown by Bekker-Jensen et al. that this is a logarithmic relationship with diminishing returns. This diminishing return is because a majority of the peptides belong to high abundance or large proteins and are highly redundant. Prior peptide-centric approaches have shown promising improvements to proteome coverage by enriching a subset of peptides containing specific amino acids for analysis rather than analyzing the whole digested proteome. By reducing the number of peptides necessary to analyze and the overall protein identification redundancy, these approaches can potentially bypass the logarithmic relationship between peptide and protein identifications. We aim to develop a peptide-centric approach that can be generally applicable for a variety of sample types by enriching a subset of peptides that have a particular physicochemical property via chromatographic approaches. Therefore, our approach is named Proteome-Selective Isolation Chromatography (P-SLICY). In this thesis, we will describe the fundamental topics within proteomics, chromatography, and mass spectrometry and the innovations towards understanding peptide chromatography to develop P-SLICY.
dc.description.noteFebruary 2025
dc.identifier.urihttp://hdl.handle.net/1993/38785
dc.language.isoeng
dc.subjectproteomics
dc.subjectchromatography
dc.subjectpeptides
dc.titleAccelerating high-throughput proteomics with proteome-selective isolation chromatography (P-SLICY)
local.subject.manitobano
oaire.awardNumberNSERC_PGSD3-560084-2021
oaire.awardTitlePostgraduate Scholarship - Doctoral
project.funder.identifierhttps://doi.org/10.13039/501100000038
project.funder.nameNatural Sciences and Engineering Research Council of Canada
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Yeung_Darien.pdf
Size:
4.91 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
770 B
Format:
Item-specific license agreed to upon submission
Description: