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Analyses intégratives de biomarqueurs immunologiques dans les études épidémiologiques. Applications à trois études cliniques

Abstract : Numerous biological processes with potentially complex interactions exist. Measurements ofthese processes allow to produce multiple biomarkers. Thus, there is a need for epidemiologyto evolve within the context of complex and multidimensional data. Immune system diseasesand associated immune disorders are an example of a field where clinical and epidemiologicalissues are increasingly complex, requiring appropriate statistical and epidemiologicalmethods. In this thesis, methods taking into account methodological difficulties generated byimmunology data are presented through three motivating examples. The general paradigm ofour approach is to take into account all measurements on a given pathology using integrativemethods. We propose principal component analysis and hierarchical clustering to summarizemultidimensional cytometry data and structural equation modelling for dealing with complexrelationships between variables in multifactorial processes. Then, through the example of anasymptotic model of immune reconstitution using an exponential function, we illustrate theimportance about the data’s structure and the biological mechanisms underlying its variabilitywhen building a mathematical model. The methods and the thinking advocated in this thesisare transposable to other research domains with complex data.
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Marie-Quitterie Picat. Analyses intégratives de biomarqueurs immunologiques dans les études épidémiologiques. Applications à trois études cliniques. Santé publique et épidémiologie. Université de Bordeaux, 2015. Français. ⟨NNT : 2015BORD0144⟩. ⟨tel-01664948⟩

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