• 4月25日 Hugues Roest Crollius: Genome wide enhancer-promoter maps in two vertebrate genomes and application to human diseases


    报告题目:Genome wide enhancer-promoter maps in two vertebrate genomes and application to human diseases
    报告人👼🏻🥧:Hugues Roest Crollius教授,巴黎高等师范学校生物研究所
    主持人🕠:翁杰敏 教授
    报告时间:2018年4月25日 13:00-14:30
    报告地点🙍🏻‍♂️:天美娱乐534小会议室
    举办单位:天美娱乐/科技处
     
    报告人简介🌂:Hugues Roest Crollius教授来自于巴黎高等师范学校☄️,是该校生物研究所的项目负责人⛹🏿🕤。Hugues Roest Crollius教授曾先后在马普所、法国埃夫里大学等从事研究工作,并多次在Nature, Cell reports, Nature Communications等著名期刊发表文章🧙🏻‍♀️。Hugues Roest Crollius教授目前的研究方向为比较基因组学,其团队通过开发新的生物信息学软件🤹🏽,利用计算分析的方法,研究基因调控的机制。
     
    报告摘要👨🏿‍🚀:Enhancers are regulatory regions which drive the fine-scale regulation of gene expression among tissues and life stages by activating promoters, sometimes over long (>100 kb) distances. Building an enhancer-promoter map of the human genome is an important goal of current research, both to better understand human development and biology but also to identify pathological mutation affecting gene expression. To address this issue, we previously developed a method to identify evolutionary conserved target genes of enhancers using comparative genomics in vertebrates. Here, we applied this method to human and zebrafish in two separate analyses and found ~50,000 putative enhancers targeting ~17,000 genes in zebrafish and ~1,300,000 putative enhancers targeting ~18,000 genes in human. Among these, a subset are conserved between the two species and define regulatory enhancers-promoter connections dating back to the ancestral vertebrate, and which are associated with development and brain functions. We also demonstrate that promoters are connected to numerous enhancers, in clear correlation with the number of tissues where they are expressed. We applied this new resource to identify possible regulatory sites mutated in patients where no coding mutation could be found as cause for their genetic disease. To do this, we trained a Random Forest classifier on two types of data (eQTLs and known active enhancers) using more than 130 functional and evolutionary genomic annotations. The new tool, Regulus, is used to prioritize non-coding variants in the context of genomic medicine.
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