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National audience; Recently, the International Association of Therapeutic Drug Monitoring (IATDMCT), that is the learning society for biological pharmacology and toxicology, issued recommendations on the therapeutic drug monitoring (TDM) of tacrolimus. This is the second consensus after the one issued in 2009. In this document, the role of tacrolimus TDM for the four principal transplanted organs is discussed. The analytical aspects, pharmacogenetics, TDM alternative approaches and the positioning of biomarkers are also presented. Stronger recommendations are about trough concentration targets in kidney and liver transplantation and for other indication of tacrolimus use. For the first time, an area under the curve of tacrolimus concentrations target is recommended for recipients management. Eventually, another set of recommendations are proposed for pharmacodynamic biomarkers used in patients’ follow-up.

National audience; Recently, the International Association of Therapeutic Drug Monitoring (IATDMCT), that is the learning society for biological pharmacology and toxicology, issued recommendations on the therapeutic drug monitoring (TDM) of tacrolimus. This is the second consensus after the one issued in 2009. In this document, the role of tacrolimus TDM for the four principal transplanted organs is discussed. The analytical aspects, pharmacogenetics, TDM alternative approaches and the positioning of biomarkers are also presented. Stronger recommendations are about trough concentration targets in kidney and liver transplantation and for other indication of tacrolimus use. For the first time, an area under the curve of tacrolimus concentrations target is recommended for recipients management. Eventually, another set of recommendations are proposed for pharmacodynamic biomarkers used in patients’ follow-up.

Efficiency of new generation sequencing methods and the reduction of their cost have led to use new methods based on big data to analyse genomic data. However, these tools require very large cohorts of samples to be used, whiwh is limited in pharmacogenomics due to access to appropriate patients and complex logistics of animal testing protocols. The ability to obtain reliable and consistent results from small cohorts remains an important challange. As part of this thesis, new bioinformatics approaches adapted to small cohorts were explored by investigation of pharmacogenes related to adverse effects of Calcineurin Inhibitors.; L'efficacité des méthodes de séquençage de nouvelle génération et la réduction de leur coût ont conduit à l'utilisation de nouvelles méthodes, basées sur le concept de l’analyse de big data, appliqué aux données génomiques. Cependant, ces outils nécessitent de très grandes cohorte d’échantillons à analyser, limitées en pharmacogénomique par l’accès aux patients appropriés ainsi que par la logistique complexe des protocoles d’expérimentation animale. La capacité de retirer des résultats fiables et cohérents à partir de petites cohortes reste donc primordiale. Dans le cadre de cette thèse, de nouvelles approches bio-informatiques adaptées aux petites cohortes ont été explorée en recherchant des pharmacogènes associés aux effets indésirables des Inhibiteurs de la Calcineurine.

Efficiency of new generation sequencing methods and the reduction of their cost have led to use new methods based on big data to analyse genomic data. However, these tools require very large cohorts of samples to be used, whiwh is limited in pharmacogenomics due to access to appropriate patients and complex logistics of animal testing protocols. The ability to obtain reliable and consistent results from small cohorts remains an important challange. As part of this thesis, new bioinformatics approaches adapted to small cohorts were explored by investigation of pharmacogenes related to adverse effects of Calcineurin Inhibitors., L'efficacité des méthodes de séquençage de nouvelle génération et la réduction de leur coût ont conduit à l'utilisation de nouvelles méthodes, basées sur le concept de l’analyse de big data, appliqué aux données génomiques. Cependant, ces outils nécessitent de très grandes cohorte d’échantillons à analyser, limitées en pharmacogénomique par l’accès aux patients appropriés ainsi que par la logistique complexe des protocoles d’expérimentation animale. La capacité de retirer des résultats fiables et cohérents à partir de petites cohortes reste donc primordiale. Dans le cadre de cette thèse, de nouvelles approches bio-informatiques adaptées aux petites cohortes ont été explorée en recherchant des pharmacogènes associés aux effets indésirables des Inhibiteurs de la Calcineurine.