Uma abordagem metabolômica global da urina de indivíduos com a Síndrome de Cri-du-chat
Data
2021-05-27
Orientadores
Assução, Nilson Antônio 
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: O objetivo deste trabalho foi avaliar o perfil metabolômico de amostras da urina de indivíduos com Síndrome de Cri du chat (SCdC), utilizando Cromatografia Líquida de Alta Performance, acoplada a Espectrometria de Massas de Alta Resolução (UHPLC-qQTof-MS/MS), visando obter informações sobre as condições fisiológicas e bioquímicas dos indivíduos portadores da SCdC, frente à indivíduos saudáveis (familiares), por meio das rotas metabólicas identificadas e dos metabólitos anotados. Métodos: Um total de noventa amostras de urina foram coletadas e divididas entre grupo teste e grupo controle, em três categorias: crianças, adolescentes e adultos. Os metabólitos foram analisados com a utilização da plataforma UHPLC-qQToF-MS/MS, com aquisição de dados no modo negativo e positivo de ionização, para todas as categorias. Os dados foram processados, utilizando-se o software DataAnalysis e Mzmine. A análise de componentes principais, as análises discriminantes de mínimos quadrados parciais e o teste t de Student, foram realizadas com o MetaboAnalyst. A anotação dos metabólitos ocorreu por meio da plataforma CEU Mass Mediator e a análise das rotas metabólicas identificadas foi realizada utilizando-se também o MetaboAnalyst. Resultados: Os resultados obtidos mostraram que 93, 116 e 61 metabólitos alterados no grupo de crianças, adolescentes e adultos, respectivamente, foram estatisticamente significantes entre os grupos controle e estudo e classificados em aminoácidos, aminas biogênicas, lipídios e purinas. As rotas metabólicas observadas estão relacionadas ao processo de metabolismo energético, distúrbios do sono, principalmente em crianças com SCdC e envelhecimento, doenças neurodegenerativas, inflamação e degradação muscular em adolescentes e adultos com SCdC, detre essas rotas, a Biossíntese da aminoacil-tRNA, Degradação da lisina, Metabolismo da cisteína e metionina, Biossíntese da arginina e Metabolismo da fenilalanina se mostraram inéditas quando comparadas aos demais trabalhos que estudaram o metabolismo das pessoas com SCdC. Conclusão: Esses resultados agregam novas perspectivas sobre o SCdC, às quais poderão contribuir com o desenvolvimento de tratamentos que possam melhorar a qualidade de vida das pessoas.
Objective: The objective of this work was to evaluate the metabolic profile of urine according to Cri du chat Syndrome (SCdC), using High Performance Liquid Chromatography, coupled with High Resolution Mass Spectrometry (UHPLC-qQTofMS / MS), obtains information on the physiological and biochemical conditions of patients with SCdC, compared to qualitative (family), through the identified metabolic routes and the metabolites noted. Methods: A total of ninety: urine samples were collected and divided between the test group and the control group, in three categories: children, adolescents and adults. The metabolites were formed using the UHPLCqQToF-MS / MS platform, with data acquisition in the negative and positive ionization mode, for all categories. The data were processed using the DataAnalysis and Mzmine software. Principal component analysis, discriminant analysis of partial combinations and Student's t test were performed with MetaboAnalyst. The annotation of the metabolites took place through the CEU Mass Mediator platform and an analysis of the identified metabolic routes was performed using also the MetaboAnalyst. Results: The results sought that 93, 116 and 61 altered metabolites in the group of children, adolescents and adults, respectively, were statistically significant between the control and study groups and classified in amino acids, biogenic amines, lipids and purines. The metabolic pathways observed are related to the energy metabolism process, sleep disorders, especially in children with SCdC and aging, neurodegenerative diseases, inflammation and muscle degradation in adolescents and adults with SCdC, between these routes, an aminoacyl-tRNA Biosynthesis, Degradation Lysine, Cysteine and Methionine Metabolism, Arginine Biosynthesis and Phenylalanine Metabolism were unpublished when compared to other studies that studied the metabolism of people with SCdC. Conclusion: These results add new perspectives on SCdC, to which they can contribute with the development of solutions that can improve people's quality of life.
Objective: The objective of this work was to evaluate the metabolic profile of urine according to Cri du chat Syndrome (SCdC), using High Performance Liquid Chromatography, coupled with High Resolution Mass Spectrometry (UHPLC-qQTofMS / MS), obtains information on the physiological and biochemical conditions of patients with SCdC, compared to qualitative (family), through the identified metabolic routes and the metabolites noted. Methods: A total of ninety: urine samples were collected and divided between the test group and the control group, in three categories: children, adolescents and adults. The metabolites were formed using the UHPLCqQToF-MS / MS platform, with data acquisition in the negative and positive ionization mode, for all categories. The data were processed using the DataAnalysis and Mzmine software. Principal component analysis, discriminant analysis of partial combinations and Student's t test were performed with MetaboAnalyst. The annotation of the metabolites took place through the CEU Mass Mediator platform and an analysis of the identified metabolic routes was performed using also the MetaboAnalyst. Results: The results sought that 93, 116 and 61 altered metabolites in the group of children, adolescents and adults, respectively, were statistically significant between the control and study groups and classified in amino acids, biogenic amines, lipids and purines. The metabolic pathways observed are related to the energy metabolism process, sleep disorders, especially in children with SCdC and aging, neurodegenerative diseases, inflammation and muscle degradation in adolescents and adults with SCdC, between these routes, an aminoacyl-tRNA Biosynthesis, Degradation Lysine, Cysteine and Methionine Metabolism, Arginine Biosynthesis and Phenylalanine Metabolism were unpublished when compared to other studies that studied the metabolism of people with SCdC. Conclusion: These results add new perspectives on SCdC, to which they can contribute with the development of solutions that can improve people's quality of life.
Descrição
Citação
ARAÚJO, Kaylanny Silva. Uma abordagem metabolômica global da urina de indivíduos com a Síndrome de Cri-du-chat. São Paulo, 2021. 128 p. Dissertação (Mestrado em Medicina Translacional) - Universidade Federal de São Paulo (UNIFESP), São Paulo, 2021.