基于ChIP-seq数据系统地挖掘具有生物学意义的转录因子和组蛋白修饰的特定组合

ChIP-seq is now the most important experiment method to study transcription factor binding sites and histone modification enrichment regions. Existing ChIP-seq data analysis methods mainly focus on peak calling. Few existing methods are satisfactory for detecting the enrichment difference of the same transcription factor or histone modification under two different biological conditions. Furthermore, current studies do not take full advantage of the large amount of public available ChIP-seq data. Based on applicant's previous work in RNA-seq and ChIP-seq data analysis and the over 5000 human/mouse ChIP-seq data sets collected and pre-processed in our lab, the first object of this project is to develop new algorithms for the identification of differential ChIP-seq data enrichment regions. Based on the differential enrichment regions and the collected ChIP-seq data, the second aim of this project is to systematically identify biologically significant combinations of several transcription factors and histone marks. This project would be very helpful for the discovery of new interactions and mechanisms among multiple transcription factors and histone marks beyond the limitation of current knowledge.

ChIP-seq 是目前最重要的研究转录因子结合位点和组蛋白修饰富集区域的实 验方法。现存的 ChIP-seq 数据分析方法大部分集中在寻找富集区域,为数不多的几个用于分析在不同条件下转录因子结合位点或组蛋白修饰变化的工作也很不成熟，对目前公共数据集中大量的 ChIP-seq 数据的利用也非常不充分。基于申请人前期在RNA-seq和ChIP-seq数据分析方面的工作以及申请人所在实验室已经收集和预处理的超过5000套人类和小鼠ChIP-seq数据，本项目的目标之一是发展ChIP-seq数据富集差异的分析算法。基于富集差异结果和收集的ChIP-seq数据，本项目的第二个目标就是系统地挖掘具有生物学意义的多个转录因子和组蛋白修饰的特定组合。本项目的研究能突破现有知识框架,对发现新的转录因子和组蛋白修饰相互作用机制具有重要的指导作用。