解密胚胎干细胞分化过程中的基因调控网络

Yisong Zhang, Kai Zhu
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摘要

随着测序技术、基因组学的发展和大数据时代的到来,生物信息学变得越来越重要。其中一个非常重要的研究领域是基因表达调控,它已成为生物信息学的热门研究领域之一。转录因子是重要的转录调控因子。在基因表达过程中,一个关键步骤是转录因子通过与特定的 DNA 序列结合来调控基因表达,抑制或增强基因表达。这些特定 DNA 序列之间的差异对于理解基因调控非常重要。随着高通量测序技术的飞速发展,结合染色质免疫共沉淀技术和新一代测序技术的 ChIP-seq 可提供全基因组转录因子结合位点的海量数据。HiChIP 作为一种以蛋白质为中心的染色质构象分析方法,因其灵敏高效的特点而备受关注。在本项目中,我们研究的是胚胎干细胞的早期去势,ZIC3、Otx2 等在其中起着重要的调控作用。我们从分析ZIC3的HiChIP数据入手,但主要是在HiChIP数据上调用峰值,并将分析HiChIP数据的工具落地。将转录因子的染色质结合特性与其他染色质标记结合起来。本报告以干细胞早期分化过程中的 HiChIP 数据为基础,比较了达到该数据峰值所需的方法。此外,该项目还利用组蛋白标记 ChIP-seq 数据(H3K27ac)的基本事实验证了输出结果,并对部分输出峰进行了主题分析。
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Deciphering the Gene Regulatory Networks during Embryonic Stem Cell Differentiation
With the development of sequencing technologies, genomics, and the advent of the era of big data, bioinformatics has become more and more important. One very important research area is the regulation of gene expression, which has become one of the hot research fields in bioinformatics. Transcription factors are important transcriptional regulators. In the process of gene expression, A key step is binding of transcription factors in gene expression by combining with a specific DNA sequence to regulate gene expression and inhibit or enhance its role. The difference between these specific DNA sequences is important for understanding gene regulation. With the rapid development of high-throughput sequencing technology, ChIP-seq, which combines chromatin immunoprecipitation technology and next-generation sequencing, provides massive data for transcription factor binding site across the genome. HiChIP, as a protein-centric chromatin conformation analysis method, is concerned because of its sensitive and efficient characteristics. In this project, we are working on the early demobilization of embryonic stem cells, in which ZIC3, Otx2, etc. play an important regulatory role. We are starting from analyzing HiChIP data on ZIC3 but mainly on calling peaks on HiChIP data, and ground tools to analysis HiChIP data. To integrate the chromatin binding properties of transcription factors with other chromatin markers. This report is based on the work done on HiChIP data during the early differentiation of stem cells, and has compared the methods required to reach the peak of this data. In addition, this project verified the output by using ground truth from histone mark ChIP-seq data (H3K27ac) and did the motif analysis from some of the output peaks.
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