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Development of mass spectrometry-based untargeted metabolomics for precision health Wang, Chenjingyi
Abstract
As the most recently emerged “omics”, metabolomics grabbed attention in human health studies by measuring thousands of small-molecule metabolites in a wide range of biological samples. As the downstream products in the biological pathway, metabolites are regarded as the closest link to the phenotypes. Small stimuli in the human body will cause relatively huge changes in the level of metabolites. Liquid chromatography-mass spectrometry (LC-MS) is the mainstay in metabolomics research due to its high throughput, sensitivity, and reliable analysis of metabolites. Nevertheless, two of the main challenges in LC-MS based metabolomics are 1) how to apply metabolomics in studying human health and 2) apart from commonly used biological samples, including serum, plasma, and urine, how to develop a methodology of new biological samples that can be adapted to specific human health research. To address those challenges, in Chapter 2, I integrated metabolomics with metagenomics to examine human gut health. 13-species metagenomic signature was selected by random forest machine learning and achieved high diagnostic accuracy in differentiating hepatic decompensation in NAFLD-related cirrhosis. The signature was cross-validated by metabolomics. 32 metabolites and 15 metabolites from serum and feces, respectively, were found to be significantly linked to 13-discriminatory species, suggesting that the identified discriminatory species may play important roles in the progression from compensated to decompensated cirrhosis. This multi-omics study yields new avenues for identifying novel targets for therapy and microbial biomarkers of hepatic decompensation, a worldwide human disease. In Chapter 3, I integrated plasma metabolomics and proteomics to examine the health conditions of highly trained females and males following acute, severe-intensity exercise. Metabolomic and proteomic homeostasis were substantially perturbed. Through statistical analysis, some metabolites and proteins were found to be closely linked to high-intensity exercise. This multi-omics study was a powerful tool to study molecular responses to acute exercise and provided a new insight to exercise-bolstered human health. In Chapter 4, I developed a new methodology to track skin secretion. Our high-performance workflow was readily applied to a wide range of skin metabolomics research to gain a better understanding of the molecular signatures on skin that link to human health and disease.
Item Metadata
Title |
Development of mass spectrometry-based untargeted metabolomics for precision health
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Creator | |
Supervisor | |
Publisher |
University of British Columbia
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Date Issued |
2022
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Description |
As the most recently emerged “omics”, metabolomics grabbed attention in human health studies by measuring thousands of small-molecule metabolites in a wide range of biological samples. As the downstream products in the biological pathway, metabolites are regarded as the closest link to the phenotypes. Small stimuli in the human body will cause relatively huge changes in the level of metabolites. Liquid chromatography-mass spectrometry (LC-MS) is the mainstay in metabolomics research due to its high throughput, sensitivity, and reliable analysis of metabolites. Nevertheless, two of the main challenges in LC-MS based metabolomics are 1) how to apply metabolomics in studying human health and 2) apart from commonly used biological samples, including serum, plasma, and urine, how to develop a methodology of new biological samples that can be adapted to specific human health research.
To address those challenges, in Chapter 2, I integrated metabolomics with metagenomics to examine human gut health. 13-species metagenomic signature was selected by random forest machine learning and achieved high diagnostic accuracy in differentiating hepatic decompensation in NAFLD-related cirrhosis. The signature was cross-validated by metabolomics. 32 metabolites and 15 metabolites from serum and feces, respectively, were found to be significantly linked to 13-discriminatory species, suggesting that the identified discriminatory species may play important roles in the progression from compensated to decompensated cirrhosis. This multi-omics study yields new avenues for identifying novel targets for therapy and microbial biomarkers of hepatic decompensation, a worldwide human disease.
In Chapter 3, I integrated plasma metabolomics and proteomics to examine the health conditions of highly trained females and males following acute, severe-intensity exercise. Metabolomic and proteomic homeostasis were substantially perturbed. Through statistical analysis, some metabolites and proteins were found to be closely linked to high-intensity exercise. This multi-omics study was a powerful tool to study molecular responses to acute exercise and provided a new insight to exercise-bolstered human health.
In Chapter 4, I developed a new methodology to track skin secretion. Our high-performance workflow was readily applied to a wide range of skin metabolomics research to gain a better understanding of the molecular signatures on skin that link to human health and disease.
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Genre | |
Type | |
Language |
eng
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Date Available |
2022-10-18
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0421299
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2022-11
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Campus | |
Scholarly Level |
Graduate
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International