Exposomics aims to characterize the totality of exposures over the lifespan, and their impact on human health. Currently, chronic exposure to harmful chemicals from air pollution and/or tobacco smoke, along with a suboptimal diet, remain leading causes for preventable mortality and morbidity worldwide. As a result, new analytical methods are needed to measure robust biomarkers of smoke exposure and food intake for improved risk assessment of clinical events. This thesis aims to develop high throughput methods to rapidly quantify urinary biomarkers of environmental smoke in high-risk occupations, and diverse global populations using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) technology. Chapter II outlines an inter-laboratory method comparison for the targeted analysis of urinary 1-hydroxypyrene (HP) when using gas chromatography-high resolution mass spectrometry (GC-HRMS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) on urine samples collected from firefighters. This work revealed the critical role of incomplete enzymatic deconjugation on method bias and underreporting of true smoke exposures. Chapter III introduces a high throughput MSI-CE-MS/MS method (< 3 min/sample) to directly analyze the intact glucuronide conjugate of HP (HP-G) in urine without complex pre-column enzyme deconjugation and derivatization procedures. Importantly, firefighters deployed under emergency conditions at the 2016 Fort McMurray wildfire had creatinine normalized HP-G concentrations below the biological exposure index, likely caused by delays in urine collection under emergency conditions, at early stages of firefighting. Chapter IV extends from targeted biomonitoring of occupational smoke exposure, towards elucidating the relative risk of tobacco smoking in an international cohort of participants (n=1000) from the Prospective Urban and Rural Epidemiological (PURE) study. Comprehensive analysis of nicotine metabolites in urine by MSI-CE-MS allowed for reliable determination of the total nicotine equivalent and nicotine metabolic ratio as robust indicators of recent tobacco smoke exposure and nicotine dependence, respectively. This method also offers a more accurate approach for biochemical verification of smoking status in large-scale epidemiological studies that are prone to social desirability and gender bias when relying on standardized questionnaires. Lastly, Chapter V employs a nontargeted metabolomics workflow using MSI-CE-MS to identify urinary metabolites that may serve as objective dietary biomarkers of food intake in participants across 14 countries from the PURE cohort. A panel of robust and generalizable metabolites were validated for biomonitoring of complex dietary exposures, that may further exacerbate the hazards of tobacco smoking. In summary, this thesis contributes high throughput analytical tools for characterizing the human urine exposome to better decipher the roles of smoke exposure, and suboptimal diet on chronic disease burden among diverse populations and regions worldwide. / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

Detta examensarbete granskar analysverktyg ur ett tvärvetenskapligt perspektiv. Det finns en hel del olika analysverktyg idag som analyserar specifika typer av omik data och därför undersöker vi hur många det finns samt vad de kan göra. Genom att definiera ett antal specifika krav såsom hur många typer av omik data den kan hantera, noggrannhet av verktygets analys så kan man se vilka som är mest lämpliga analysverktygen när det gäller kartläggning av omik data. Resultaten visar att det idag inte finns analysverktyg som uppfyller de specifikt angivna kraven eller huvudsyftet genom testning av programvaran. Ingenuity analysverktyget är det närmaste vi kan komma för de krav som vi söker. På begäran av slutanvändaren testades två analysverktyg för att se om en kombination av dessa kan uppfylla slut användarens krav. Analysverktyget Uniprot batch converter testas med FEvER men resultat är inte framgångsrikt, då kombinationen av dessa verktyg inte är bättre än Ingenuity analysverktyget. Fokus vänds mot en alternativ kombination som är en hemsida och heter NCBI. Hemsidan har en sökmotor kopplad till flera olika analysverktyg som är gratis att använda. Genom sökmotorn kan ”omik” data kombineras och mer än ett inmatat värde kan hanteras i taget. Eftersom tekniken snabbt går framåt innebär det däremot att nya analysverktyg behövs för data hantering och inom en snar framtid så har vi kanske ett analysverktyg som uppfyller kraven av slutanvändarna. / This thesis examines PATs from a multidisciplinary view. There are a lot of PAT's existing today analyzing specific type of omics data, therefore we investigate them and what they can do. By defining some specific requirements such as how many omics data types it can handle, the accuracy of the PAT can be obtained to get the most suitable PAT when it comes to mapping omics data to pathways. Results show that no PATs found today fulfills the specific set of requirements or the main goal though software testing. The Ingenuity PAT is the closest to fulfill the requirements. Requested by the end user, two PATs are tested in combination to see if these can fulfill the requirements of the end user. Uniprot batch converter was tested with FEvER and results did not turn out successfully since the combination of the two PATs is no better than the Ingenuity PAT. Focus then turned to an alternative combination, a homepage called NCBI that have search engines connected to several free PATs available thus fulfilling the requirements. Through the search engine “omics” data can be combined and more than one input can be taken at a time. Since technology is rapidly moving forward, the need for new tools for data interpretation also grows. It means that in a near future we may be able to find a PAT that fulfills the requirements of the end users.