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Analyse métabolomique multidimensionnelle : applications aux erreurs innées du métabolisme

Abstract : The new field of precision medicine is revolutionizing current medical practice and reshaping future medicine. Precision medicine intends to put the patient as the central driver of healthcare by broadening biological knowledge and acknowledging the great diversity of individuals. The prediction of physiological and pathological states in patients requires a dynamic and systemic understanding of these interactions. Inborn errors of metabolism (IEM) are genetic disorders resulting from defects in a given biochemical pathway due to the deficiency of an enzyme, its cofactor or a transporter. IEM are no longer considered to be monogenic diseases, which adds another layer of complexity to their characterization and diagnosis. To meet this need for faster screening, the metabolic profile can be a promising candidate given its ability in disease screening, biomarker discovery and metabolic pathway investigation. In this thesis, we used a metabolomic approach which is particularly relevant for IEM given their basic pathophysiology that is tightly related to metabolism. This thesis allowed the implementation of an untargeted metabolomic methodology based on a multidimensional analytical strategy including high-resolution mass spectrometry coupled with ultra-high-performance liquid chromatography and ion mobility. This work also set a methodology for preprocessing, analysis and interpretation of the generated data using experimental design and multivariate data analysis. Finally, the strategy is applied to the exploration of IEM with mucopolysaccharidoses as a proof of concept. The results suggest a major remodeling of the amino acid metabolisms in mucopolysaccharidosis type I. In summary, metabolomic is a relevant complementary tool to support the genomic approach in the functional investigations and diagnosis of IEM.
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https://tel.archives-ouvertes.fr/tel-01689845
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Submitted on : Monday, January 22, 2018 - 2:55:11 PM
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  • HAL Id : tel-01689845, version 1

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Abdellah Tebani. Analyse métabolomique multidimensionnelle : applications aux erreurs innées du métabolisme. Endocrinologie et métabolisme. Normandie Université, 2017. Français. ⟨NNT : 2017NORMR043⟩. ⟨tel-01689845⟩

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