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La construction du réseau de régulation transcriptionnelle

Abstract : This PhD project takes place in List MAPS, a Horizon 2020-funded Marie Curie Actions InnovativeTraining Network (ITN) with the goal of understandingof the ecology of Listeria monocytogenesthrough the combination of high throughput Epigenetics, Deep sequencing of transcripts, Proteomics, Bioinformatics, Mathematics and Microbiology. Acentralobjective of the ITN is to decipher the mechanismsunderlying adaptation and virulence of L. monocytogenes“from farm to fork”.This PhD project (subproject9) aims to tackle the task of transcription regulatorynetwork construction. A significant part of regulationat the transcriptional level is achieved by modulationof transcription initiation rate. In bacteria, transcriptioninitiation relies on recognition of particular sequencemotif by a Sigma-factor approximately 10 bpupstream of the transcription start site (TSS) and ismodulated by the binding of transcription factors recognizingother sequence motifs located nearby. RNASeqtranscriptomics provides direct information on therepertoire of TSSs and transcription units and therebyoffers renewed perspectives to address the problemof transcription factor binding sites identification. Thegoal of this PhD project is to assess existing toolsand to develop new methods for prediction of TF bindingsites by combining expression profiles and preciseinformation on the location of the TSSs. Severalapproaches based on position weight matrix (PWM)models will be investigated to extend the classicalmixture model by relaxing the hypothesis that motifscorresponding to different TF binding sites occur independentlybetween TSS regions.In the new model,we will explicitly account for the increased probabilityof occurrence of a same motif in two promoters whentheir profiles of activity across conditions are similar. A particular attention will also be paid to the positionof the motif with respect to the TSS and the sigmafactor binding site. In parallel to the methodologicaldevelopments we will also work on the use of theseapproaches to build the transcription regulatory networkof L. monocytogenes based on data form theliterature and from the List MAPS project. Finally, wewish to use the information on the regulatory networkto tackle a particular point relevant for the List MAPSproject using a dedicated model.
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Islam Sultan. La construction du réseau de régulation transcriptionnelle. Statistiques [math.ST]. Université Paris-Saclay, 2019. Français. ⟨NNT : 2019SACLS184⟩. ⟨tel-02373468⟩

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