Recherche statistique de biomarqueurs du cancer et de l'allergie à l'arachide

Olivier Collignon 1, 2
2 TOSCA
INRIA Lorraine, CRISAM - Inria Sophia Antipolis - Méditerranée , UHP - Université Henri Poincaré - Nancy 1, Université Nancy 2, INPL - Institut National Polytechnique de Lorraine, CNRS - Centre National de la Recherche Scientifique : UMR7502
Abstract : The first part of this doctoral dissertation deals with the research of cancer biomarkers. During transcription it was observed that some nucleotides are replaced mistakenly by others. We sought to compare the probabilities of these transcription infidelities in mRNA originating from normal and cancerous tissues. To do this, a multiple testing procedure was performed on the positions of 17 genes by considering their ESTs (Expressed Sequence Tag). The conclusion was reached that the proportions of these transcription errors are mainly increased in cancer tissues as compared to normal ones. This phenomenon would lead to the translation of aberrant proteins, whose detection could help in identifying patients with cancer. The main goals of the second part are the diagnosis of peanut allergy and the prediction of its severity. Diagnosing peanut allergy and evaluating the intensity of the symptoms are currently accomplished with a double blind placebo controlled food challenge (DBPCFC). Patients are given increasing peanut doses until the first clinical reaction appears. Since DBPCFC can result in life-threatening responses, we propose an alternate procedure with the long term goal of replacing invasive allergy tests. Discriminant analyses of peanut allergy, DBPCFC score, the eliciting dose and the first accidental exposure score were performed in 243 allergic patients using 6 immunoassays and 30 skin prick tests. A Multiple Factorial Analysis was performed to use new factors as predictors. We also developed an algorithm for simultaneously clustering eliciting dose values and selecting discriminant variables. Our main conclusion is that antibody measurements provide information on the allergy and its severity, especially those directed against the peanut allergens rAra-h1, rAra-h2 and rAra-h3.
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Olivier Collignon. Recherche statistique de biomarqueurs du cancer et de l'allergie à l'arachide. Mathématiques [math]. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10074⟩. ⟨tel-01748338v2⟩

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