Développement de nouveaux outils pour l'intégration des données du ChIP-Seq et leurs applications pour l'étude du contrôle de la transcription

Authors: Joly Beauparlant, Charles
Advisor: Droit, ArnaudCorbeil, Jacques
Abstract: Recent progress in sequencing technologies opened the possibility of performing very complex research experiments. Combined with the vast public datasets produced by intenational consortiums such as ENCODE, Roadmap Epigenomics and Fantoms, the amount of data to process can be daunting. The goal of my doctoral project is to develop new bioinformatic approaches to facilitate the integration of ChIP-Seq data for the study of the dynamic of the interactions between proteins and DNA. New tools such as ENCODExplorer and FantomTSS were developped in R to make the publicly available datasets easier to integrate. Futhermore, the metagene package allows the comparison of enrichment patterns of DNA-interacting proteins. This package efficiently extracts read coverage from genomic regions of interest, normalize the signal and uses controls to remove background noise. The main functionnality of the metagene package is to visually compare enrichment profiles from multiple groups of genomic regions and to offer statistical tools to caracterize and compare those profiles. To validate my experimental approach, I used over a hundred datasets from the GM12878 cell line produced by the ENCODE consortium to study the enrichment profiles of transcription factors and histones in enhnacer and promoter regions. I was able to define two distinct recruitment patterns: the gradient effect and the threshold effect. With the ever growing complexity of genomic datasets, it is essential to develop new methodotical approaches to allow a better understanding of the underlying biological processes. ENCODExplorer and metagene are both available on Bioconductor.
Document Type: Thèse de doctorat
Issue Date: 2017
Open Access Date: 24 April 2018
Permalink: http://hdl.handle.net/20.500.11794/28115
Grantor: Université Laval
Collection:Thèses et mémoires

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