東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back to Search results for [ null ]

Switch To: Labeled | MARC Mode | ISBD

Expanding Coverage of the Chemical E...

Bloszies, Clayton S.

Linked to FindBook

Google Book

Amazon

博客來

Expanding Coverage of the Chemical Exposome Using Novel Data Acquisition and Computational Tools.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Expanding Coverage of the Chemical Exposome Using Novel Data Acquisition and Computational Tools./
Author:	Bloszies, Clayton S.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	117 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-05, Section: B.
Contained By:	Dissertations Abstracts International82-05B.
Subject:	Environmental science. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28093393
ISBN:	9798691214301

Expanding Coverage of the Chemical Exposome Using Novel Data Acquisition and Computational Tools.
Bloszies, Clayton S.

Expanding Coverage of the Chemical Exposome Using Novel Data Acquisition and Computational Tools. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 117 p.

Source: Dissertations Abstracts International, Volume: 82-05, Section: B.

Thesis (Ph.D.)--University of California, Davis, 2020.

This item must not be sold to any third party vendors.

The chemical exposome encompasses the sum of all exposures during an individual's lifetime. This group of compounds, when combined with genetic traits, determine chronic disease, thus, to fully understand human health issues, it is imperative to improve exposome measurements to match genomic technologies. My dissertation focuses on expanding the coverage of the chemical exposome and developing tools and techniques that will increase the reliability of untargeted mass spectrometry based studies.In Chapter 1, I address the many challenges faced when trying to measure all compounds contained within the chemical exposome. Exposome compounds cover a large range of biological concentration, many different structural classes, and are extensively modified in the body via detoxification pathways. I explore the potential strategies researchers can employ to address these difficulties, from instrumental acquisition and sample preparation, to compound identification and other data processing tools.In Chapter 2, I discuss the utilization of hydrogen-deuterium exchange (HDX) for identifying unknown compounds in metabolomics and exposomics studies. HDX is a method by which all of the acidic protons in a compound are exchanged with deuterium prior to mass spectrometric analysis with the goal of using the resulting mass shift to illuminate potential substructures. In this work, we compared the efficacy of different deuterium incorporation methods, explored the filtering potential of this method on 253 test compounds and large chemical databases, and identified 101 compounds in mouse mammary tumors. The results of this study show that HDX can alleviate researchers' reliance on mass spectral databases for identifying compounds in biological samples. Chapter 3 focuses on an untargeted exposomics method that was developed to measure chemical exposures that influence female reproductive health. In the human body, xenobiotic compounds are transformed through metabolism to increase polarity and allow for excretion in the urine. These transformations commonly consist of phase I hydroxylation reactions mediated by CYP450 enzymes and phase II conjugations mediated by transferases. In the urine, the most common conjugate forms are glucuronides and sulfates. Our urinary exposomics method takes advantage of this knowledge. By using B-glucuronidase/aryl sulfatase, we can cleave the phase II conjugates into their phase I forms, and easily extract these less polar analytes from the polar urinary matrix. This method was used to measure exposure compounds in 50 women from Orange County, CA at three different time points. The compound measurements were then used to build linear mixed effects models to predict the chemical variables that influence hormonally derived endocrine endpoints. Models were built for menstrual cycle length, cycle peak luteinizing hormone, follicular estrone-1,3-glucuronide, and estrone-1,3-glucuronide slope. Chemical variables that had not previously been associated with reproductive function were identified for each of these endocrine endpoints. These models illuminate novel chemical exposures for future causative studies on reproductive health.

ISBN: 9798691214301Subjects--Topical Terms:

677245
Environmental science.
Subjects--Index Terms:

Compound identification

Expanding Coverage of the Chemical Exposome Using Novel Data Acquisition and Computational Tools.
LDR:04550nmm a2200433 4500 001 2276366
005 20210503061417.5
008 220723s2020 ||||||||||||||||| ||eng d
020 $a 9798691214301
035 $a (MiAaPQ)AAI28093393
035 $a AAI28093393
040 $a MiAaPQ $c MiAaPQ
100 1 $a Bloszies, Clayton S. $3 3554650
245 1 0 $a Expanding Coverage of the Chemical Exposome Using Novel Data Acquisition and Computational Tools.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 117 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-05, Section: B.
500 $a Advisor: Fiehn, Oliver.
502 $a Thesis (Ph.D.)--University of California, Davis, 2020.
506 $a This item must not be sold to any third party vendors.
520 $a The chemical exposome encompasses the sum of all exposures during an individual's lifetime. This group of compounds, when combined with genetic traits, determine chronic disease, thus, to fully understand human health issues, it is imperative to improve exposome measurements to match genomic technologies. My dissertation focuses on expanding the coverage of the chemical exposome and developing tools and techniques that will increase the reliability of untargeted mass spectrometry based studies.In Chapter 1, I address the many challenges faced when trying to measure all compounds contained within the chemical exposome. Exposome compounds cover a large range of biological concentration, many different structural classes, and are extensively modified in the body via detoxification pathways. I explore the potential strategies researchers can employ to address these difficulties, from instrumental acquisition and sample preparation, to compound identification and other data processing tools.In Chapter 2, I discuss the utilization of hydrogen-deuterium exchange (HDX) for identifying unknown compounds in metabolomics and exposomics studies. HDX is a method by which all of the acidic protons in a compound are exchanged with deuterium prior to mass spectrometric analysis with the goal of using the resulting mass shift to illuminate potential substructures. In this work, we compared the efficacy of different deuterium incorporation methods, explored the filtering potential of this method on 253 test compounds and large chemical databases, and identified 101 compounds in mouse mammary tumors. The results of this study show that HDX can alleviate researchers' reliance on mass spectral databases for identifying compounds in biological samples. Chapter 3 focuses on an untargeted exposomics method that was developed to measure chemical exposures that influence female reproductive health. In the human body, xenobiotic compounds are transformed through metabolism to increase polarity and allow for excretion in the urine. These transformations commonly consist of phase I hydroxylation reactions mediated by CYP450 enzymes and phase II conjugations mediated by transferases. In the urine, the most common conjugate forms are glucuronides and sulfates. Our urinary exposomics method takes advantage of this knowledge. By using B-glucuronidase/aryl sulfatase, we can cleave the phase II conjugates into their phase I forms, and easily extract these less polar analytes from the polar urinary matrix. This method was used to measure exposure compounds in 50 women from Orange County, CA at three different time points. The compound measurements were then used to build linear mixed effects models to predict the chemical variables that influence hormonally derived endocrine endpoints. Models were built for menstrual cycle length, cycle peak luteinizing hormone, follicular estrone-1,3-glucuronide, and estrone-1,3-glucuronide slope. Chemical variables that had not previously been associated with reproductive function were identified for each of these endocrine endpoints. These models illuminate novel chemical exposures for future causative studies on reproductive health.
590 $a School code: 0029.
650 4 $a Environmental science. $3 677245
650 4 $a Biochemistry. $3 518028
650 4 $a Analytical chemistry. $3 3168300
650 4 $a Public health. $3 534748
650 4 $a Genetics. $3 530508
653 $a Compound identification
653 $a Exposomics
653 $a Hydrogen-deuterium exchange
653 $a Metabolomics
653 $a Untargeted mass Spectrometry
653 $a Reproductive health
653 $a Genetic traits
653 $a Genomic technologies
690 $a 0768
690 $a 0487
690 $a 0486
690 $a 0369
690 $a 0573
710 2 $a University of California, Davis. $b Agricultural and Environmental Chemistry. $3 1678688
773 0 $t Dissertations Abstracts International $g 82-05B.
790 $a 0029
791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28093393