Dissertations / Theses on the topic 'Mass spectrometry metabolomic'
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Yang, Zhiyi. "Mass spectrometry-based metabolomic and lipidomic characterization of esophageal cancer and lung cancer." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/819.
Full textOrlowsky, Andrea. "Development of an ambient ionisation mass spectrometry method for metabolomic analysis of blood microsamples." Thesis, Orlowsky, Andrea (2021) Development of an ambient ionisation mass spectrometry method for metabolomic analysis of blood microsamples. Masters by Research thesis, Murdoch University, 2021. https://researchrepository.murdoch.edu.au/id/eprint/63786/.
Full textDelabrière, Alexis. "New approaches for processing and annotations of high-throughput metabolomic data obtained by mass spectrometry." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS359/document.
Full textMetabolomics is a phenotyping approach with promising prospects for the diagnosis and monitoring of several diseases. The most widely used observation technique in metabolomics is mass spectrometry (MS). Recent technological developments have significantly increased the size and complexity of data. This thesis focused on two bottlenecks in the processing of these data, the extraction of peaks from raw data and the annotation of MS/MS spectra. The first part of the thesis focused on the development of a new peak detection algorithm for Flow Injection Analysis (FIA) data, a high-throughput metabolomics technique. A model derived from the physics of the mass spectrometer taking into account the saturation of the instrument has been proposed. This model includes a peak common to all metabolites and a specific saturation phenomenon for each ion. This model has made it possible to create a workflow that estimates the common peak on well-behaved signals, then uses it to perform matched filtration on all signals. Its effectiveness on real data has been studied and it has been shown that proFIA is superior to existing algorithms, has good reproducibility and is very close to manual measurements made by an expert on several types of devices. The second part of this thesis focused on the development of a tool for detecting the structural similarities of a set of fragmentation spectra. To do this, a new graphical representation has been proposed, which does not require the metabolite formula. The graphs are also a natural representation of MS/MS spectra. Some properties of these graphs have then made it possible to create an efficient algorithm for detecting frequent subgraphs (FSM) based on the generation of trees covering graphs. This tool has been tested on two different data sets and has proven its speed and interpretability compared to state-of-the-art algorithms. These two algorithms have been implemented in R, proFIA and mineMS2 packages available to the community
Cardoso, Patrícia [UNESP]. "Metabolomic evaluation of interactions in rhizosphere between Senna spectabilis and associated microorganisms." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/135954.
Full textSenna spectabilis é uma planta medicinal detentora de inumeras aplicações terapêuticas tradicionais. Como uma fonte rica de metabólitos com atividades biológicas a rizosfera de S. spectabilis foi o objeto de estudo neste trabalho. O conhecimento da população da microbiota da rizosfera contribuiu para a compreensão das interações que poderiam ocorrer nessa região dinâmica e rica do solo. Um número de métodos moleculares têm sido desenvolvidos nos últimos anos para o estudo da comunidade microbiana utilizando PCR no sequenciamento das regiões de rRNA 16S e ITS. Os objetivos deste estudo foram identificar a população microbiana da rizosfera de mudas de S. spectabilis e em sequência selecionar algumas linhagens e submetê-las a cultivos mistos em meio sólido. A identificação foi conseguida através do 454-pyrosequenciamento das raízes e sequenciamento por iluminaseq das soluções nutritivas em que as plantas foram cultivadas. Os resultados mostraram uma população rica e variada de bactérias e fungos, com destaque aos filos Verrucomicrobia, Proteobacterias, Firmicutes para as bactérias e para os fungos os filos Basidiomycota e Ascomycota. Espécies selecionadas de fungos foram cultivados em meio Czapek-dox líquido e uma análise do perfil metabólico foi conduzido utilizando HPLC-DAD e HPLC-DAD/MS. Entre os metabólitos detectados nessa pré-avaliação estão os derivados policetidicos produzidos por Fusarium: zearalenonas, conhecidas micotoxinas produzidas por uma grande quantidade de espécies deste gênero. Estes resultados induziram a seleção de cinco fungos de Fusarium, Paecilomyces e uma espécie de bactéria, Burkholderia sp para o cultivo misto em meio de agar sólido. O objetivo foi detectar mudanças na produção metabólica e analisar as alterações esperadas por RMN de 1H associados aos métodos quimiométricos de análise PCA e PLS e tambem por LC/MS. Uma série de...
Senna spectabilis is a medicinal plant with innumeral traditional therapeutic applications. As a source of rich metabolites with biological activities S. spectabilis' rhizosphere was the object of study in this work. The knowledge of the population of the microbiota of the rhizosphere contributes to the understanding of the interactions that may occur in this dynamic and rich region of the soil. A number of molecular methods have been developed in recent years to study the microbial community using PCR associated in the sequencing of 16S and ITS regions of rRNA. The objectives of this study were to identify the microbial population of rhizosphere seedlings of S. spectabilis and in sequence to select a few strains and submit them to co-cultures in a solid medium. Identification was achieved with 454- pyrosequencing of roots and iluminaseq sequencing of the hydroponic solutions, in which the seedlings were cultivated. Results showed a rich and varied population of bacteria and fungi notably the bacteria phyla Verrucromiobia, Proteobacteria, Firmicutes and for the fungi the phyla Basidiomycota and Ascomycota. Selected species of fungi were cultivated in liquid Czapek-dox medium and a screening of the metabolic profile was conducted using HPLC-DAD and HPLC-DAD/MS. Among the metabolites detected in this previous evaluation are the polyketides derivates produced by Fusarium: zearalenones known as mycotoxins produced by many species of this genus. These results have induced to the selection of five fungi from Fusarium, Paecilomyces and one specie of bacteria, Burkholderia sp for mix cultivation in agar solid medium. The aim was to detect changes in the metabolic production and analyse the expected alterations by 1H NMR associated with chemometric method PCA and PLS and LC/MS. A series of enniatin could be detected by LC/MS indicating that co-culturing induced the modifications in the...
Cardoso, Patrícia. "Metabolomic evaluation of interactions in rhizosphere between Senna spectabilis and associated microorganisms /." Araraquara, 2015. http://hdl.handle.net/11449/135954.
Full textBanca: Luis Vitor Silva do Sacramento
Banca: Cíntia Duarte de Freitas Milagre
Banca: Mônica Tallarico Pupo
Banca: Christopher Scott Jeffrey
Resumo: Senna spectabilis é uma planta medicinal detentora de inumeras aplicações terapêuticas tradicionais. Como uma fonte rica de metabólitos com atividades biológicas a rizosfera de S. spectabilis foi o objeto de estudo neste trabalho. O conhecimento da população da microbiota da rizosfera contribuiu para a compreensão das interações que poderiam ocorrer nessa região dinâmica e rica do solo. Um número de métodos moleculares têm sido desenvolvidos nos últimos anos para o estudo da comunidade microbiana utilizando PCR no sequenciamento das regiões de rRNA 16S e ITS. Os objetivos deste estudo foram identificar a população microbiana da rizosfera de mudas de S. spectabilis e em sequência selecionar algumas linhagens e submetê-las a cultivos mistos em meio sólido. A identificação foi conseguida através do 454-pyrosequenciamento das raízes e sequenciamento por iluminaseq das soluções nutritivas em que as plantas foram cultivadas. Os resultados mostraram uma população rica e variada de bactérias e fungos, com destaque aos filos Verrucomicrobia, Proteobacterias, Firmicutes para as bactérias e para os fungos os filos Basidiomycota e Ascomycota. Espécies selecionadas de fungos foram cultivados em meio Czapek-dox líquido e uma análise do perfil metabólico foi conduzido utilizando HPLC-DAD e HPLC-DAD/MS. Entre os metabólitos detectados nessa pré-avaliação estão os derivados policetidicos produzidos por Fusarium: zearalenonas, conhecidas micotoxinas produzidas por uma grande quantidade de espécies deste gênero. Estes resultados induziram a seleção de cinco fungos de Fusarium, Paecilomyces e uma espécie de bactéria, Burkholderia sp para o cultivo misto em meio de agar sólido. O objetivo foi detectar mudanças na produção metabólica e analisar as alterações esperadas por RMN de 1H associados aos métodos quimiométricos de análise PCA e PLS e tambem por LC/MS. Uma série de...
Abstract: Senna spectabilis is a medicinal plant with innumeral traditional therapeutic applications. As a source of rich metabolites with biological activities S. spectabilis' rhizosphere was the object of study in this work. The knowledge of the population of the microbiota of the rhizosphere contributes to the understanding of the interactions that may occur in this dynamic and rich region of the soil. A number of molecular methods have been developed in recent years to study the microbial community using PCR associated in the sequencing of 16S and ITS regions of rRNA. The objectives of this study were to identify the microbial population of rhizosphere seedlings of S. spectabilis and in sequence to select a few strains and submit them to co-cultures in a solid medium. Identification was achieved with 454- pyrosequencing of roots and iluminaseq sequencing of the hydroponic solutions, in which the seedlings were cultivated. Results showed a rich and varied population of bacteria and fungi notably the bacteria phyla Verrucromiobia, Proteobacteria, Firmicutes and for the fungi the phyla Basidiomycota and Ascomycota. Selected species of fungi were cultivated in liquid Czapek-dox medium and a screening of the metabolic profile was conducted using HPLC-DAD and HPLC-DAD/MS. Among the metabolites detected in this previous evaluation are the polyketides derivates produced by Fusarium: zearalenones known as mycotoxins produced by many species of this genus. These results have induced to the selection of five fungi from Fusarium, Paecilomyces and one specie of bacteria, Burkholderia sp for mix cultivation in agar solid medium. The aim was to detect changes in the metabolic production and analyse the expected alterations by 1H NMR associated with chemometric method PCA and PLS and LC/MS. A series of enniatin could be detected by LC/MS indicating that co-culturing induced the modifications in the...
Doutor
Childs, Stephen Andrew. "Liquid chromatography and mass spectrometry based metabolomic investigations of sulphur containing metabolites in human prostate cancer." Thesis, University of Sunderland, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702720.
Full textVallabhaneni, Prashanthi. "Metabolomic approaches to understanding the auxin and ethylene response in Arabidopsis roots." Thesis, Virginia Tech, 2012. http://hdl.handle.net/10919/76838.
Full textMaster of Science
Marsol, i. Vall Alexis. "Gas chromatography-mass spectrometry for the analysis of metabolomic compounds in agrifood products. New methods and applications." Doctoral thesis, Universitat de Lleida, 2017. http://hdl.handle.net/10803/403491.
Full textThis Doctoral Thesis focuses on the development of novel gas chromatography coupled to mass spectrometry (GC-MS) techniques and the application of some existing methods to the analysis of fruit and fruit-derived samples. The thesis is divided in three parts attending the approaches studied. Initially, a comprehensive two-dimensional gas chromatography (GC×GC-MS) method was developed by testing several column configurations to analyse apples and peaches. In the second part of the Thesis, three new methods based on injection-port derivatization were developed. The first consisted on a targeted analysis of 17 glycosylated and non-glycosylated polyphenols in fruit and fruit juice samples. The second method was devoted to the analysis of HMF and patulin, two compounds used as markers of quality in the fruit juice industry. The last method developed in this part was focused on the free lipophilic fraction of fruit juices. In this case, a dispersive liquid-liquid microextraction (DLLME) preceded in-port derivatization. The third part was devoted to the analysis of volatile and semi-volatile compounds in several fruit-derived products, namely fruit fibres deriving from the juice industry and four samples of peach juices consisting in two varieties (yellow and red-fleshed) and two distinct processing procedures for each variety (freshly blended and commercial).
Esta Tesis Doctoral se centra en el desarrollo de nuevos métodos de cromatografía de gases acoplada a técnicas de espectrometría de masas (GC-MS) y a la aplicación de algunos métodos existentes al análisis de muestras de frutas y derivados. La tesis se divide en tres partes según los enfoques estudiados. Inicialmente, se desarrolló un método de cromatografía de gases bidimensional comprensiva (GC×GC-MS) en la que se probaron varias configuraciones de columnas. En la segunda parte de la Tesis, se desarrollaron tres nuevos métodos basados en la derivatización en el puerto de inyección. La primera consistió en un análisis selectivo de 17 polifenoles glicosilados y no glicosilados en muestras de fruta y zumo de fruta. El segundo método se dedicó al análisis de HMF y patulina, dos compuestos utilizados como marcadores de calidad en la industria del zumo de frutas. El último método desarrollado en esta parte se centró en la fracción lipofílica libre de zumos de fruta. En este caso, una microextracción líquido-líquido dispersiva (DLLME) precedió a la derivatización en el puerto. La tercera parte se dedicó al análisis de los compuestos volátiles y semi-volátiles de varios derivados de la fruta, a saber, fibras de fruta derivadas de la industria de los zumos y cuatro muestras de zumos de melocotón consistentes en dos variedades (amarillo y rojo) y dos procedimientos de elaboración para cada variedad (recién licuado y comercial).
Alonezi, Sanad M. Z. "Metabolomic profiling of the effects of melittin and cisplatin on ovarian cancer cells using high resolution mass spectrometry." Thesis, University of Strathclyde, 2017. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=28650.
Full textDenbigh, Joanna. "Lipidomic and metabolomic analysis of biological response mechanisms in cancer cells : a multidisciplinary approach." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/lipidomic-and-metabolomic-analysis-of-biological-response-mechanisms-in-cancer-cells-a-multidisciplinary-approach(a1f04b8e-0f79-497a-9928-18a59a8e9cb0).html.
Full textMohler, Rachel E. "Discovery based yeast metabolomic analysis using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry and chemometrics /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/11578.
Full textJaeger, Frederick Howard. "Simplified Plant Sample Preparation for use in Gas Chromatography-Mass Spectrometry (GC-MS) Based Metabolomic Profiling and Targeted Analyte Quantitation." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-02202008-155316/.
Full textRobertson, Francesca Pamela. "The application of proteomic and metabolomic mass spectrometry strategies for the characterization and detection of processed animal proteins in animal feeds." Thesis, University of London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529475.
Full textAbbiss, Hayley. "Gas chromatography-mass spectrometry-based untargeted metabolomic analysis of organ tissue, plasma and urine samples from a Rat Model of polycystic kidney disease." Thesis, Abbiss, Hayley (2018) Gas chromatography-mass spectrometry-based untargeted metabolomic analysis of organ tissue, plasma and urine samples from a Rat Model of polycystic kidney disease. PhD thesis, Murdoch University, 2018. https://researchrepository.murdoch.edu.au/id/eprint/41472/.
Full textFall, Fanta. "Étude métabolomique de la polarisation des macrophages pulmonaires humains A split-range acquisition method for the non-targeted metabolomic profiling of human plasma with hydrophilic interaction chromatography - high-resolution mass spectrometry Metabolomic changes during the M1- and M2-polarization of human lung macrophages." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLV064.
Full textLung macrophages are essential immune cells for defense against pathogens that colonize the respiratory tract and are also involved in the pathophysiology of inflammatory lung diseases such as asthma. Macrophages can be subject to polarization towards two phenotypes called M1 and M2. The M1 phenotype is induced by Toll-like Receptor agonists and promotes the inflammatory response while the M2 phenotype is induced by the canonical Th2 cytokines IL-4 and IL-13 and mainly performs immunoregulatory functions. This differentiation results in changes in phenotype (expression of membrane proteins, production of cytokines) and cellular functions. Polarization also has an impact on metabolism and the production of intracellular mediators.Our objective was to characterize the metabolomic alterations occurring during the M1/M2 polarization in human lung macrophages. Initially, non-targeted and targeted metabolomic methods by liquid chromatography coupled with high-resolution mass spectrometry and gas chromatography coupled with mass spectrometry were developed. These approaches were then applied to identify altered metabolic pathways during M1/M2 polarization (Krebs cycle, kynurenin and arachidonic acid pathways) and to quantify the mediators involved in regulating the inflammatory response, including oxysterols. This work provides a better understanding of cellular metabolism during the polarization of human lung macrophages
Riccio, Maria Francesca. "Uso da espectrometria de massas como ferramenta metabolômica e controle de qualidade de óleos vegetais e gorduras animais." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311827.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Este trabalho direcionou-se ao controle de qualidade de óleos vegetais e gorduras animais pelo emprego de análise de baixa massa molecular pela técnica EASI-MS utilizando a ferramenta metabolômica. As matérias-primas graxas (óleos e gorduras vegetais e animais) e os produtos sintetizados a partir destes insumos são misturas complexas, com aplicações e valores agregados variados como por exemplo para a nutrição humana, aplicações industriais na produção de lubrificantes, biodiesel, plasticidas, surfactantes, entre outros. As técnicas disponíveis como Cromatografia gasosa (GC) com detector de ionização de chama (FID) ou acoplada a um espectrômetro de massas (GC-MS) tem sido as técnicas mais utilizadas para caracterizar óleos e gorduras, através da determinação da composição de ácidos graxos. Como a caracterização da composição graxa destas matrizes são muitas vezes restritas, exigindo a necessidade de procedimentos laboriosos como extrações, purificações que requerem muito tempo utilizamos neste trabalho uma recente técnica de ionização ambiente de espectrometria de massas: EASI-MS (easy ambient sonic-spray ionization mass spectrometry) na caracterização de óleos vegetais e gorduras animais que dispensa o emprego de processos de derivatização química e a separação cromatográfica. Neste trabalho aplicamos a metabolômica para elucidação de um conjugado de marcadores taxonômicos de óleos nunca observados ou analisados em conjunto antes, principalmente ácidos graxos e bifenóis os quais podem ser extraídos de maneira simples e eficaz. Para a caracterização dos componentes existentes no metaboloma de óleos de origem vegetal e animal e para a caracterização de azeites de oliva de diferentes procedências, uma simples extração com uma solução hidroalcoólica foi utilizada. O extrato foi adicionados à uma superfície de vidro para dessa forma, serem injetados para dentro do equipamento de massas e então analisados. O equipamento utilizado foi um Q-TrapTM utilizando uma fonte de EASI construída por pesquisadores do Laboratório ThoMSon de espectrometria de massas (IQ/UNICAMP). Os espectros de massas obtidos demonstraram a presença de ácidos graxos livres além de bifenóis característicos de cada tipo de óleo ou gordura analisado. A presença na mesma análise (espectro) demonstrou que mesmo para amostras complexas, a técnica se mostra aplicável para a identificação, caracterização e controle de qualidade de maneira inequívoca para óleos e gorduras
Abstract: This work is directed to quality control of vegetable oils and animal fats by the use of low molecular analysis of the EASI-MS technique using the metabolomics tool. Raw materials greases (oils and vegetable and animal fats) and the products synthesized from these inputs are complex mixtures, with varying applications and value added such as for human nutrition, industrial applications in the lubrificants production, biodiesel, plasticity, surfactants, among others. The available techniques such as chromatography (GC) with flame ionization detector (FID) and coupled to a mass spectrometer (GC-MS) has been the most widely used techniques to characterize oils and fats by determining the fatty acid composition. To characterize the grease composition of these matrices are often restricted, requiring the need of laborious procedures such as extractions, purifications that require much time, in this work we used a recent technique ambient ionization mass spectrometry: EASI-MS (Easy ambient sonic-spray ionization mass spectrometry) in the characterization of vegetable oils and animal fats does not require the use of chemical derivatization procedures and chromatographic separation. In this work we have applied metabolomics to elucidate a combination of taxonomic markers oils never observed or analyzed together before, mainly fatty acids and biphenols which can be extracted in a simple and effective process. To characterize the metabolome of existing components in vegetable oils and animal and for the characterization of olive oils from different sources, a simple extraction with a water-methanol solution was used. The extract was added to a glass surface to thereby be injected into the spectrometer and then analyzed. The equipment used was a Q-TrapTM using a source of EASI built by researchers at the Thomson Laboratory of mass spectrometry (Institute of Chemistry / UNICAMP). The mass spectra obtained showed the presence of free fatty acids besides biphenols characteristic of each type of oil or fat analyzed. The presence in the same analysis (spectrum) showed that even for complex samples, the technique proves to be applicable to the identification, characterization and quality control unequivocally for oils and fats
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas
Rocha, Cláudia Manuela Mesquita da. "Metabolic signature of lung cancer: a metabolomic study of human tissues and biofluids." Doctoral thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/13957.
Full textThis thesis reports the application of metabolomics to human tissues and biofluids (blood plasma and urine) to unveil the metabolic signature of primary lung cancer. In Chapter 1, a brief introduction on lung cancer epidemiology and pathogenesis, together with a review of the main metabolic dysregulations known to be associated with cancer, is presented. The metabolomics approach is also described, addressing the analytical and statistical methods employed, as well as the current state of the art on its application to clinical lung cancer studies. Chapter 2 provides the experimental details of this work, in regard to the subjects enrolled, sample collection and analysis, and data processing. In Chapter 3, the metabolic characterization of intact lung tissues (from 56 patients) by proton High Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is described. After careful assessment of acquisition conditions and thorough spectral assignment (over 50 metabolites identified), the metabolic profiles of tumour and adjacent control tissues were compared through multivariate analysis. The two tissue classes could be discriminated with 97% accuracy, with 13 metabolites significantly accounting for this discrimination: glucose and acetate (depleted in tumours), together with lactate, alanine, glutamate, GSH, taurine, creatine, phosphocholine, glycerophosphocholine, phosphoethanolamine, uracil nucleotides and peptides (increased in tumours). Some of these variations corroborated typical features of cancer metabolism (e.g., upregulated glycolysis and glutaminolysis), while others suggested less known pathways (e.g., antioxidant protection, protein degradation) to play important roles. Another major and novel finding described in this chapter was the dependence of this metabolic signature on tumour histological subtype. While main alterations in adenocarcinomas (AdC) related to phospholipid and protein metabolisms, squamous cell carcinomas (SqCC) were found to have stronger glycolytic and glutaminolytic profiles, making it possible to build a valid classification model to discriminate these two subtypes. Chapter 4 reports the NMR metabolomic study of blood plasma from over 100 patients and near 100 healthy controls, the multivariate model built having afforded a classification rate of 87%. The two groups were found to differ significantly in the levels of lactate, pyruvate, acetoacetate, LDL+VLDL lipoproteins and glycoproteins (increased in patients), together with glutamine, histidine, valine, methanol, HDL lipoproteins and two unassigned compounds (decreased in patients). Interestingly, these variations were detected from initial disease stages and the magnitude of some of them depended on the histological type, although not allowing AdC vs. SqCC discrimination. Moreover, it is shown in this chapter that age mismatch between control and cancer groups could not be ruled out as a possible confounding factor, and exploratory external validation afforded a classification rate of 85%. The NMR profiling of urine from lung cancer patients and healthy controls is presented in Chapter 5. Compared to plasma, the classification model built with urinary profiles resulted in a superior classification rate (97%). After careful assessment of possible bias from gender, age and smoking habits, a set of 19 metabolites was proposed to be cancer-related (out of which 3 were unknowns and 6 were partially identified as N-acetylated metabolites). As for plasma, these variations were detected regardless of disease stage and showed some dependency on histological subtype, the AdC vs. SqCC model built showing modest predictive power. In addition, preliminary external validation of the urine-based classification model afforded 100% sensitivity and 90% specificity, which are exciting results in terms of potential for future clinical application. Chapter 6 describes the analysis of urine from a subset of patients by a different profiling technique, namely, Ultra-Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC-MS). Although the identification of discriminant metabolites was very limited, multivariate models showed high classification rate and predictive power, thus reinforcing the value of urine in the context of lung cancer diagnosis. Finally, the main conclusions of this thesis are presented in Chapter 7, highlighting the potential of integrated metabolomics of tissues and biofluids to improve current understanding of lung cancer altered metabolism and to reveal new marker profiles with diagnostic value.
A presente tese reporta a aplicação da metabolómica ao estudo de tecidos e biofluidos humanos (plasma sanguíneo e urina), com o intuito de caracterizar a assinatura metabólica do cancro pulmonar primário. No Capítulo 1, apresenta-se uma breve introdução sobre a epidemiologia e a patogénese deste tipo de cancro, bem como um sumário das principais alterações metabólicas tipicamente associadas ao cancro em geral. Descreve-se ainda a abordagem metabolómica, nomeadamente os métodos analíticos e estatísticos utilizados, assim como o estado da arte da sua aplicação em estudos clínicos do cancro do pulmão. No Capítulo 2, apresentam-se os detalhes experimentais deste trabalho, no que diz respeito ao grupo de indivíduos envolvidos, à colheita e análise das amostras e ao posterior tratamento dos dados. O Capítulo 3 descreve a caracterização metabólica de tecidos do pulmão (de 56 doentes) por espetroscopia de Ressonância Magnética Nuclear (RMN) de alta resolução com rotação no ângulo mágico. Após a otimização cuidada das condições de aquisição e a identificação detalhada dos sinais espetrais (mais de 50 metabolitos identificados), os perfis metabólicos dos tumores e dos tecidos adjacentes não envolvidos (controlos) foram comparados por análise multivariada, tendo sido discriminados com uma exatidão de 97%. Os metabolitos que mais significativamente contribuíram para esta diferenciação foram: glucose e acetato (diminuídos nos tumores), lactato, alanina, glutamato, GSH, taurina, creatina, fosfocolina, glicerofosfocolina, fosfoetanolamina, nucleótidos de uracilo e péptidos (aumentados nos tumores). Algumas destas variações corroboraram alterações típicas do metabolismo do cancro (e.g., glicólise e glutaminólise aumentadas), enquanto outras sugeriram novas pistas sobre a possível relevância de processos como a proteção antioxidante e a degradação proteica. Um outro resultado novo e importante descrito neste capítulo foi a dependência da assinatura metabólica em relação ao tipo histológico do tumor. Enquanto as principais alterações observadas nos adenocarcinomas (AdC) se relacionaram com o metabolismo fosfolipídico e proteico, os carcinomas de células escamosas (SqCC) apresentaram perfis glicolíticos e glutaminolíticos mais pronunciados, sendo possível construir um modelo válido para a discriminação destes subtipos. No Capítulo 4, apresenta-se o estudo metabolómico por RMN de plasma sanguíneo de mais de 100 doentes e quase 100 controlos saudáveis, do qual resultou um modelo multivariado com uma taxa de classificação de 87%. A distinção entre os grupos foi feita essencialmente com base nos níveis de lactato, piruvato, acetoacetato, lipoproteínas LDL+VLDL e glicoproteínas (aumentados nos doentes), juntamente com os níveis de glutamina, histidina, valina, metanol, lipoproteínas HDL e dois compostos não identificados (diminuídos nos doentes). Estas variações foram detetadas desde os estádios iniciais da doença e a magnitude de algumas delas dependeu do tipo histológico, embora não permitindo discriminar AdC de SqCC. Para além disso, mostra-se neste capítulo que o desequilíbrio dos grupos controlo e cancro em termos da idade dos indivíduos poderá ter alguma influência nos resultados, e apresenta-se uma tentativa exploratória de validação externa, que resultou numa taxa de classificação de 85%. O estudo por RMN do perfil metabólico da urina dos doentes com cancro do pulmão e dos controlos é apresentado no Capítulo 5. Comparativamente ao plasma, o modelo construído com os perfis urinários apresentou uma taxa de classificação superior (97%). Após uma avaliação cuidada da possível influência do género, idade e hábitos tabágicos, um conjunto de 19 metabolitos foi proposto como estando relacionado com a doença (incluindo 3 compostos desconhecidos e 6 parcialmente identificados como metabolitos N-acetilados). Tal como no caso do plasma, estas variações foram detetadas em doentes no estádio inicial e mostraram alguma dependência em relação ao tipo histológico, obtendo-se um modelo válido para a discriminação AdC vs. SqCC, ainda que com um poder preditivo modesto. Para além disso, o teste preliminar de validação externa revelou 100% de sensibilidade e 90% de especificidade, o que é um resultado bastante promissor em termos da potencial utilização dos perfis urinários em aplicações clínicas futuras. No Capitulo 6, descreve-se a caracterização dos perfis metabólicos da urina (de um subgrupo de indivíduos) por cromatografia líquida de ultra-eficiência acoplada a espetrometria de massa (UPLC-MS). Embora não avançando muito na identificação estrutural de possíveis marcadores, este estudo reforçou o valor diagnóstico da urina, já que os modelos multivariados resultantes apresentaram taxa de classificação e poder preditivo elevados. Finalmente, no Capítulo 7, apresentam-se as principais conclusões deste trabalho, realçando o contributo da metabolómica integrada de tecidos e biofluidos para a compreensão do metabolismo alterado do cancro do pulmão e para a deteção de novos perfis marcadores com valor diagnóstico.
Pino, Rius Antoni del. "Development and application of analytical methods to characterise processed fruit and vegetable products." Doctoral thesis, Universitat de Lleida, 2017. http://hdl.handle.net/10803/459296.
Full textThis thesis presents an approach to the development and application of analytical methodologies to characterise metabolite compounds in processed fruit and vegtable products from the agroindustry. In this thesis were developed UPLC-PDA-MS/MS methods to determine carotenoids and chlorophylls and their derivatives in processed fruit and vegetable products. The method developed to analyse carotenoids was applied to study the changes in the carotenoid profile of commercial monovarietal fruit juices and the developed to analyse chlorophyll and their derivatives was applied to assess the fate of chlorophylls in processed vegetable products. In addition, various methodologies and techniques were applied to characterise processed fibres obtained from juice industry by-products. The phenolic compounds of the fibres were determined and a comparison of its content and profile in lyophilised fresh fruit was established. Additionally metabolite profile and content of the fibres was characterised, and compared with data reported in previous literature for the corresponding fresh fruit. Finally, with the aim of obtain a methodology to authenticate monovarietal fruit juices, were used nuclear magnetic resonance spectroscopy (NMR) to analyse primary metabolites and UPLC-PDA-MS/MS to determine phenolic compounds combined chemometric tools such as principal component analysis
Esta tesis se centra en el desarrollo y aplicación de metodologías analíticas para caracterizar los metabolitos en productos de fruta y verdura procesados provenientes de la agroindustria. En esta tesis se han desarrollado métodos de UPLC-PDA-MS / MS para determinar los carotenoides y clorofila • las y sus derivados en productos de frutas y verduras. El método de análisis de carotenoides se aplicó para estudiar los cambios en el perfil de carotenoides en zumos de fruta monovarietales y el desarrollado para analizar las clorofila • las y derivados se aplicó para evaluar la transformación de las clorofila • en productos vegetales procesados. Además, se aplicaron diversas metodologías y técnicas para caracterizar fibras procesadas obtenidas a partir de subproductos de la industria del zumo. Los compuestos fenólicos de las fibras se determinaron y se estableció una comparación de su contenido y perfil con el determinado en fruta fresca liofilizada. También se caracterizaron los metabolitos primarios y secundarios, y se compararon con los datos reportados en la literatura para la fruta fresca correspondiente. Finalmente, con el objetivo de obtener una metodología para autenticar los zumos de fruta monovarietales, se utilizó la resonancia magnética nuclear (RMN) para analizar metabolitos primarios y UPLC-PDA-MS / MS para determinar los compuestos fenólicos los cuales combinados con herramientas quimiométricas como el análisis de componentes principales.
Beisken, Stephan Andreas. "Informatics for tandem mass spectrometry-based metabolomics." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708325.
Full textLuan, Hemi. "Mass spectrometry based metabolomics for biomarkers of Parkinson's disease." HKBU Institutional Repository, 2017. https://repository.hkbu.edu.hk/etd_oa/396.
Full textJones, Christina Michele. "Applications and challenges in mass spectrometry-based untargeted metabolomics." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54830.
Full textAbdelrazig, Salah M. A. "Mass spectrometry for high-throughput metabolomics analysis of urine." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/30600/.
Full textRobinson, Sarah Jane. "Mass spectrometric approaches to carbohydrate metabolomics in monocotyledons." Thesis, University of York, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423682.
Full textKapoore, Rahul Vijay. "Mass spectrometry based hyphenated techniques for microalgal and mammalian metabolomics." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/8234/.
Full textTengstrand, Erik. "Data analysis of non-targeted mass spectrometry experiments." Doctoral thesis, Stockholms universitet, Institutionen för miljövetenskap och analytisk kemi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-116820.
Full textAt the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Submitted.
Malkar, Aditya. "Analytical methods based on ion mobility and mass spectrometry for metabolomics." Thesis, Loughborough University, 2014. https://dspace.lboro.ac.uk/2134/14524.
Full textHuang, He. "Mass Spectrometry-Based Metabolomics: Platform Development and Application to Neurodegenerative Disease." University of Akron / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1496678565947565.
Full textGipson, Geoffrey T. Sokhansanj Bahrad. "Discovery Of discriminative LC-MS and 1H NMR metabolomics markers /." Philadelphia, Pa. : Drexel University, 2008. http://hdl.handle.net/1860/2766.
Full textDomingo, Almenara Xavier. "Automated mass spectrometry-based metabolomics data processing by blind source separation methods." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/397799.
Full textUna de las principales limitaciones de la metabolómica es la transformación de datos crudos en información biológica. Además, la metabolómica basada en espectrometría de masas genera grandes cantidades de datos complejos caracterizados por la co-elución de compuestos y artefactos experimentales. El objetivo de esta tesis es desarrollar estrategias automatizadas basadas en deconvolución ciega de la señal para mejorar las capacidades de los métodos existentes que tratan las limitaciones de los diferentes pasos del procesamiento de datos en metabolómica. El objetivo de esta tesis es también desarrollar herramientas capaces de ejecutar el flujo de trabajo del procesamiento de datos en metabolómica, que incluye el preprocessamiento de datos, deconvolución espectral, alineamiento e identificación. Como resultado, tres nuevos métodos automáticos para deconvolución espectral basados en deconvolución ciega de la señal fueron desarrollados. Estos métodos fueron incluidos en dos herramientas computacionales que permiten convertir automáticamente datos crudos en información biológica interpretable y por lo tanto, permiten resolver hipótesis biológicas y adquirir nuevos conocimientos biológicos.
One of the major bottlenecks in metabolomics is to convert raw data samples into biological interpretable information. Moreover, mass spectrometry-based metabolomics generates large and complex datasets characterized by co-eluting compounds and with experimental artifacts. This thesis main objective is to develop automated strategies based on blind source separation to improve the capabilities of the current methods that tackle the different metabolomics data processing workflow steps limitations. Also, the objective of this thesis is to develop tools capable of performing the entire metabolomics workflow for GC--MS, including pre-processing, spectral deconvolution, alignment and identification. As a result, three new automated methods for spectral deconvolution based on blind source separation were developed. These methods were embedded into two computation tools able to automatedly convert raw data into biological interpretable information and thus, allow resolving biological answers and discovering new biological insights.
Hodson, M. P. "The application of liquid chromatography-mass spectrometry to metabolomics, toxicology and systems biology." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604133.
Full textTong, Lily Victoria. "Development and application of mass spectrometry-based metabolomics methods for disease biomarker identification." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/46014.
Full textMIT Science Library copy printed in leaves.
Includes bibliographical references (p. 281-299).
Human societies face diverse health challenges including a rapidly aging population, rising incidence of metabolic disease, and increasing antibiotic resistance. These problems involve complex interactions between genes and environment and are often not well understood. To address these challenges, high-throughput and reproducible advances in genome sequencing, transcript measurement, and protein measurement have been developed; the information resulting from these techniques has led to an increased understanding of cellular function and the identification of number of novel biomarkers for a variety of diseases.In recent years, the monitoring of such systems-level cellular behavior has naturally extended to the metabolite level, leading to the study of metabolomics. The rise of metabolomics corresponds hand in hand with the desire to address some of the phenotypic informational gaps left behind from genomics, transcriptomics, and proteomics. The study of metabolites carries several advantages. First, the number of metabolites in the human "metabolome," estimated at 2500 metabolites, remains a tractable number for analysis as compared to the 35,000 genes and 100,000-1,000,000 proteins. Metabolites also reliably provide an instantaneous "downstream" biochemical snapshot of a cell, and the typical metabolomics analysis is carried out on relatively noninvasive patient fluids such as urine or plasma.The goal of this thesis is to design, develop, and apply methods for the metabolomic analysis of blood via gas chromatography-mass spectrometry (GC-MS) instrumentation. Despite initial successes, methods in metabolomics vary widely and have not been standardized. This was first addressed via the optimization of the instrumentation itself, a topic rarely addressed in the literature but crucial toward the reliable identification of biomarkers.
(cont) We investigated the different GC-MS parameters found to have the largest impact on data quality and employed D-optimal design to pare down the search space to a feasible number of experiments. These parameters were then optimized via response surface estimation to ensure maximum reproducibility and sensitivity of the entire metabolite mixture. The results from this optimization constitute a significant improvement upon existing methods in the literature.Next, methods were developed for the bioinformatics analysis of raw GC-MS data. Current techniques for metabolite tracking are non-systematic and typically require the laborious use of reference libraries. We developed a method to track conserved metabolites across GC-MS replicates and conditions with the optional use of reference libraries and validated it an E. coli dataset and the differential detection of metabolites in a spiked mixture. In addition, we investigated the best methods for the imputation of missing data as applied to three different metabolomics datasets; to this date, missing data imputation has not been comprehensively addressed in the metabolomics literature, and many methods currently used are needlessly inaccurate. After investigating eight different imputation methods via three deletion methods, it was concluded that k-nearest neighbor algorithms were the best and most accurate method for data imputation.Finally, the instrumental parameter optimization and metabolite tracking methods were applied to the problem of predicting patient mortality in end-stage renal disease (ESRD). Although ESRD is a complex and well-studied disease, known risk factors only account for 50% of patient deaths, and prediction accuracies for the disease remain relatively low; in addition, mortality rates in the first 90 days of dialysis treatment are double that after 90 days.
(cont.) We sought to investigate whether the addition of metabolomic information would result in increased accuracy of mortality prediction. One hundred twenty patient samples were obtained from a national dialysis study (equally representing death and survival within 90 days of starting dialysis) and analyzed according to our protocol. Two feature selection algorithms were applied to identify significant metabolites distinguishing death and survival, and the corresponding models resulted in improved receiver-operating characteristic (ROC) curve areas of 0.85 and 0.93. This result constitutes a significant improvement from existing clinical models, which at best result in ROC curve areas of 0.80. Based on this work, we hypothesize that our observed differential fatty acid concentrations are indicative of impaired fatty acid oxidation, leading to insulin resistance in ESRD patients (regardless of Type II diabetes status) and eventually, patient mortality.
by Lily Victoria Tong.
Ph.D.
Alamri, Hassan. "DISCOVERY OF PATHWAYS LINKED TO CARDIOVASCULAR DISEASE RISK BY MASS SPECTROMETRY-BASED METABOLOMICS." Cleveland State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=csu1513168141266115.
Full textLi, Xiaona. "Mass spectrometry-based metabolomics study on KRAS-mutant colorectal cancer and rheumatoid arthritis." HKBU Institutional Repository, 2018. https://repository.hkbu.edu.hk/etd_oa/540.
Full textGullberg, Jonas. "Metabolomics : a tool for studying plant biology /." Umeå : Dept. of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, 2005. http://epsilon.slu.se/200588.pdf.
Full textMörén, Lina. "Metabolomics and proteomics studies of brain tumors : a chemometric bioinformatics approach." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111309.
Full textFernández, Albert Francesc. "Machine learning methods for the analysis of liquid chromatography-mass spectrometry datasets in metabolomics." Doctoral thesis, Universitat Politècnica de Catalunya, 2014. http://hdl.handle.net/10803/283980.
Full textChetwynd, Andrew John. "Development of nanoflow liquid chromatography-nanoelectrospray ionization mass spectrometry methodology for improved urine metabolomics." Thesis, University of Sussex, 2015. http://sro.sussex.ac.uk/id/eprint/56253/.
Full textYang, Kundi. "Assessing and Evaluating Biomarkers and Chemical Markers by Targeted and Untargeted Mass Spectrometry-based Metabolomics." Miami University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=miami1605044640528563.
Full textTimischl, Birgit. "Hyphenated mass spectrometric methods for quantitative metabolomics in E. coli and human cells." kostenfrei, 2008. http://www.opus-bayern.de/uni-regensburg/volltexte/2008/1028/.
Full textPervukhin, Anton. "Molecular formula identification using high resolution mass spectrometry algorithms and applications in metabolomics and proteomics /." kostenfrei, 2009. http://d-nb.info/1001408578/34.
Full textKopka, Joachim. "Applied metabolome analysis : exploration, development and application of gas chromatography-mass spectrometry based metabolite profiling technologies." Thesis, Universität Potsdam, 2008. http://opus.kobv.de/ubp/volltexte/2010/4059/.
Full textDie Aufnahme von Nährstoffen und ihre chemische Umwandlung mittels Reaktionen, die Energie und Baustoffe für Wachstum und Vermehrung bereitstellen, ist eine grundlegende Eigenschaft des Lebens. Diese Eigenschaft wird Stoffwechsel oder, wie im Folgenden, Metabolismus genannt. Im Verlauf der Evolution war alles Leben abhängig von solchen Reaktionen, die essentielle und allen Lebensformen gemeinsame Moleküle erzeugen. Über diese sogenannten Primärmetabolite hinaus sind hochdiverse Reaktionen entstanden. Diese erlauben Organismen, einzigartige sogenannte Sekundärmetabolite zu produzieren, die in der Regel einen zusätzlichen Überlebensvorteil vermitteln. Die Gesamtheit aller Metabolite, die von dem komplexen Reaktionsnetzwerk in Organismen erzeugt werden, nennt man seit 1998 das Metabolom. Die Größe des Metaboloms kann nur geschätzt werden. Neben der Gesamtheit aller Metabolite werden heute drei weitere Arten an Molekülen als wesentlich betrachtet, um die Phänomene des Lebens zu verstehen: erstens die Proteine, deren Summe, das Proteom, auch die Enzyme einschließt, die die obigen metabolischen Reaktionen durchführen, zweitens die Ribonukleinsäuren (RNS), deren Gesamtheit als Transkriptom bezeichnet wird, und drittens die doppelsträngige Desoxyribonukleinsäure (DNS), die das Genom, die Summe aller Gene eines Organismus, ausmacht. Die Untersuchung aller dieser vier molekularen Ebenen des Lebens erfordert Technologien, die idealerweise die vollständige Analyse der Gesamtheit aller DNS-, RNS-, Protein-Moleküle, bzw. Metabolite erlauben. Zu Beginn meiner Arbeiten waren solche Technologien für DNS, RNS, und Proteine verfügbar, aber nicht für Metabolite. Aus diesem Grund habe ich meine Forschungstätigkeit auf das Ziel ausgerichtet, so viele Metabolite wie irgend möglich in einer gemeinsamen Analyse zu erfassen. Zu diesem Zweck habe ich mich auf eine einzelne Technik, nämlich die gekoppelte Gaschromatographie und Massenspektrometrie, kurz GC-MS, konzentriert. Nicht zuletzt durch meine Arbeiten ist GC-MS heute eine der am häufigsten angewandten Technologien und unverzichtbar für das breite Durchmustern der Metabolite. Neben der Etablierung der grundlegenden GC-MS-Profilanalyse-Technologie liegen die Haupterrungenschaften meiner Arbeiten sowohl in den technischen Neuerungen als auch in den Einsichten in metabolische Mechanismen, die es Pflanzen erlauben, erfolgreich auf Umwelteinflüsse zu reagieren. Die technologischen Errungenschaften waren erstens wesentliche Beiträge zur Labor-Automatisierung und zur Auswertung von modernen, auf Flugzeitmassenspektrometrie beruhenden, GC-MS-Profilanalysen, zweitens die Entwicklung einer entsprechenden Prozessierungs-Software, genannt TagFinder, und drittens die Etablierung einer internationalen Datensammlung zur Metabolitidentifizierung aus komplexen Mischungen. Diese massenspektralen und gaschromatographischen Daten haben seit 2005 Eingang in die von mir initiierte Entwicklung der Golm Metabolom Datenbank (GMD) gefunden, die die zunehmend wachsenden GC-MS-Referenzdaten wie auch die Metabolitprofildaten verwaltet und öffentlich zugänglich macht. Darüber hinaus wurden die langfristigen Ziele einer verbesserten Präzision für relative und absolute Quantifizierung wie auch einer Kopplung von Konzentrationsbestimmung und metabolischen Flussanalysen mittels GC-MS verfolgt. Sowohl die Stoffmengen als auch die Geschwindigkeit der Stoffaufnahme und der chemischen Umsetzung, d.h. der metabolische Fluss, sind wesentlich für neue biologische Einsichten. In diesem Zusammenhang wurde von mir die Aufnahme von CO2 durch Pflanzen, der Basis allen Lebens auf der Erde, untersucht. Angewandt auf das Temperaturstress- und Salzstressverhalten von Modell- und Kulturpflanzen, nämlich des Ackerschmalwands (Arabidopsis thaliana), des Hornklees (Lotus japonicus) und der global bedeutendsten Nutzpflanze Reis (Oryza sativa), wurden detaillierte und vergleichende neue metabolische Einsichten in den Zeitverlauf der Temperaturanpassung und die Anpassung an zunehmend salzhaltige Böden erzielt. Metabolismus verändert sich unter diesen Bedingungen allmählich fortschreitend und nicht in plötzlichen Übergängen. Am Beispiel des Hornklees konnte gezeigt werden, dass Metabolitprofilanalysen eine hohe Vorhersagekraft für die Biomasseerzeugung unter Salzeinfluss wie auch für die Aufnahme von Salz durch die Pflanze haben. So mag es in Zukunft möglich werden, GC-MS-Profilanaysen anzuwenden, um den Züchtungsprozess von Kulturpflanzen zu beschleunigen.
Vinayavekhin, Nawaporn. "Metabolomics Strategies for Discovery of Biologically Active or Novel Metabolites." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10150.
Full textChemistry and Chemical Biology
Puschmann, Robert. "Analysis and Quantification of Inositol Poly- and Pyrophosphates by NMR Spectroscopy and Mass Spectrometry." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21044.
Full textInositol pyrophosphates (PP-InsPs) are a well conserved group of second messengers that are involved in a plethora of cellular processes including phosphate homeostasis, insulin signaling, and apoptosis. Despite much effort, it is still mostly unknown how PP-InsPs exert their diverse functions. In order to decipher the mechanisms, researchers have relied either on metabolic labeling with radioactive inositol or on electrophoretic separation on polyacrylamide gels but these methods either lack ease of use or sensitivity. Therefore, two new analytical tools, based on nuclear magnetic resonance (NMR) spectroscopy, and liquid chromatography coupled mass spectrometry (LCMS), were developed. To overcome the limited sensitivity provided by NMR spectroscopy, a high yielding synthesis of NMR-active 13C-labeled inositol was designed and optimized. Furthermore, a chemoenzymatic synthesis of all mammalian PP-InsPs isomers was developed that relied on a scalable purification strategy utilizing precipitation with Mg2+ ions. Human cells were metabolically labeled with 13C-inositol and the prepared PP-InsPs were used as standards to identify peaks in the NMRspectra. These fingerprint signals enabled the quantification of the corresponding molecules. The LCMS-based method was based on the derivatization of the highly charged inositol pyrophosphates to their corresponding methyl esters by trimethylsilyldiazomethane. The permethylated InsPs and PP-InsPs were suitable for LC separation and MS measurement, and provide a sensitivity unmatched by NMR spectroscopy. The method was established using inositol hexakisphosphate, a simpler analog of PP-InsPs, and methylated InsP6 could be detected at quantities as low as 10 femtomole. However, the adaptation of the derivatization for PP-InsPs proved challenging as the reaction caused degradation of the analyte but strategies to circumvent the decay by changing the derivatization agent to diazomethane were promising.
Samino, Gené Sara. "Mass spectrometry and nuclear magnetic resonance based metabolomics applied to the study of polycystic ovary syndrome." Doctoral thesis, Universitat Rovira i Virgili, 2013. http://hdl.handle.net/10803/128209.
Full textObjetivos: El presente trabajo tiene dos objetivos generalizables que han sido estudiados con más detalle en la presente tesis doctoral. El primero de ellos es mejorar aspectos metodológicos en el ámbito de la metabolómica y el segundo ha sido la aplicación de la metabolómica en el estudio del síndrome del ovario poliquístico (PCOS). Resultados: Del primer objetivo se han realizado dos trabajos: en el primero, la optimización de un método de extracción común para analizar muestras biológicas en dos plataformas analíticas complementarias utilizadas en metabolómica como son la resonancia magnética nuclear y la espectrometría de masas. Del segundo trabajo realizado se han obtenido unas pautas para abordar los retos que surgen del análisis de datos de metabolómica en espectrometría de masas. Del segundo objetivo también han sido realizados dos trabajos: en ambos se ha utilizado la metabolómica no dirigida para abordar el estudio del PCOS. En el primer trabajo, se ha utilizado la metabolómica para conocer el impacto que ejerce la obesidad en los trastornos metabólicos asociados al PCOS. En el segundo trabajo, se ha utilizado la metabolómica no dirigida para evaluar como afecta la aplicación de una politerapia con medicamentos al metabolismo de pacientes con PCOS. Conclusión: La metabolómica puede ser utilizada como una nueva herramienta para estudiar los trastornos metabólicos.
Wei, Juntong. "Mass spectrometry-based metabolomics to unveil the polybrominated diphenyl ether-47 induced alteration in breast carcinoma." HKBU Institutional Repository, 2019. https://repository.hkbu.edu.hk/etd_oa/661.
Full textAgana, Bernice A. "Mass Spectrometry-Based Proteomics and Metabolomics: Understanding Protein Interactions, Proteome Complexity and Perturbations in Cellular Metabolism." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574636665012436.
Full textVogl, Franziska C. [Verfasser], and Peter [Akademischer Betreuer] Oefner. "Methodical aspects of urinary metabolomics by liquid chromatography-mass spectrometry / Franziska C. Vogl ; Betreuer: Peter Oefner." Regensburg : Universitätsbibliothek Regensburg, 2020. http://d-nb.info/1212240227/34.
Full textCrighton, Elly Gwyn. "Are supplements supplemented? Evaluating the composition of complementary and alternative medicines using mass spectrometry and metabolomics." Thesis, Crighton, Elly Gwyn (2020) Are supplements supplemented? Evaluating the composition of complementary and alternative medicines using mass spectrometry and metabolomics. PhD thesis, Murdoch University, 2020. https://researchrepository.murdoch.edu.au/id/eprint/57740/.
Full textWang, Yu. "The Application of Metabolomics to the Evaluation of the Celllular Toxicity." University of Akron / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1397057769.
Full textShowiheen, Salah Ali A. "Metabolomics profiling of amino acids metabolism in osteoarthritis." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/123249/1/Salah%20Ali%20A_Showiheen_Thesis.pdf.
Full text