项目名称: 基于小鼠胚胎干细胞研究DNA羟甲基化降噪算法及其去甲基化相关调控机制
项目编号: No.31200949
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 遗传学与生物信息学、细胞生物学
项目作者: 赵倩
作者单位: 同济大学
项目金额: 22万元
中文摘要: 近年科学家提出TET1蛋白可将甲基化胞嘧啶(mC)催化形成羟甲基化胞嘧啶(hmC),这一发现掀起了研究DNA去甲基化机制的热潮。申请人自2010年起一直与此领域顶尖专家合作研究小鼠胚胎干细胞中hmC相关机制。我们的前期工作发现,虽然很多研究团队产生了高通量hmC数据,但即使同一细胞系、同一实验技术产生的hmC数据间仍有较大误差,这必然会阻碍我们对hmC的真正认识;另外目前尚未有工作系统研究hmC与转录调控相关组学数据的关联性。因此,申请人拟基于整合概率模型,发展算法,以降低mES中由于hmC高通量实验所带来的误差,得到相对可靠的hmC信号;并应用Jaccard Index算法,系统而全面地研究mES中hmC与其他转录调控数据之间的相关性,进而揭示hmC所参与的DNA去甲基化过程中相关调控机制。希望本课题能够推动DNA去甲基化机制的研究进程,最终应用于疾病(如癌症、神经褪行性疾病等)的治疗。
中文关键词: DNA甲基化;DNA羟甲基化;样品异质性;癌症;
英文摘要: In recent years, scientists found that TET1 could catalyze mC to hmC. The groundbreaking discovery opened a door for understanding the mechanism of DNA demethylation and made hmC analysis a hotspot. The applicant has been collaborated with the top scientist in hmC research field since 2010. According to our previous results, we found although lots of hmC high throughput sequencing data sets in mouse embryonic stem cell (mES) were generated, bias existed among the same cell line and the same experiment, which prevented us from understanding the real hmC world; furthermore, there has no systematic study for hmC and other regulatory "omics"data yet. Therefore, we hope for developing "integrated probabilistic modeling" based algorithms to eliminate the systematic bias from hmC experiments, on behalf of which can we get the more reliable hmC data; and applying Jaccard Index algorithm to systematically uncover the regulatory mechanisms of hmC involved DNA demethylation procedure. We hope this project will promote the study of DNA demethylation mechanism and eventually be applied to the disease (such as cancer, neurodegenerative diseases, etc.) treatment.
英文关键词: DNA Methylation;DNA Hydroxymethylation;Sample Heterogeneity;Tumor;