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A l’assaut du puzzle transcriptomique : optimisations, applications et nouvelles méthodes d’analyse pour le RNA-Seq

Abstract : Since their introduction, next generation sequencing technologies (NGS) have shaped our vision of the transcriptome. RNA-seq, or high throughput transcript sequencing, enables the fast digitization of a transcriptome in the form of million of short DNA sequences. The information available in the raw data can be used in a quantitative way to extract expression profiles. The obtained sequences also provides a wide range of qualitative information such as splicing junction, genomic or post-transcriptional variants, as well as new forms of less conventional transcription such as circular RNA, fusion genes or long non coding RNA. Gradually, RNA-Seq is becoming a gold standard in molecular biology and tomorrow in genomic medicine.My thesis work proposes a global vision of the RNA-Seq technology, starting with the optimisation of current analysis methods to a particular context through systematic benchmarking procedures relying on the simulation on synthetic data. These optimizations are later used as a part of a work on the biology of cancer in order to identify new biomarkers in leukemia as well as a new stratification of hepatoblastoma patients to propose personalized treatments. Finally, my last work is focused on the proposal of two new analysis methods for RNA-Seq data, both based on the principle of k-mer decomposition. The first method, TranSiPedia, is a new paradigm to integrate transcriptome data at a very large scale through the systematic indexation of experimental data. The second method, DE-Kupl, is a new strategy to perform differential analysis, without a priori knowledge about the transcriptome. DE-kupl is designed to help the discovery of new biomarkers as well as the characterization of new mechanisms of the transcriptome.
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Submitted on : Friday, September 8, 2017 - 11:18:08 AM
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Jérôme Audoux. A l’assaut du puzzle transcriptomique : optimisations, applications et nouvelles méthodes d’analyse pour le RNA-Seq. Médecine humaine et pathologie. Université Montpellier, 2017. Français. ⟨NNT : 2017MONTT012⟩. ⟨tel-01584017⟩



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