De novo deciphering three-dimensional chromatin interaction and topological domains by wavelet transformation of epigenetic profiles.
De novo deciphering three-dimensional chromatin interaction and topological domains by wavelet transformation of epigenetic profiles.
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通过表观遗传图谱的小波变换从头破译三维染色质相互作用和拓扑结构域
DOI：
10.1093/nar/gkw225
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发表时间：
2016-06-20
影响因子：
14.9
通讯作者：
Zhang MQ
中科院分区：
文献类型：
--
作者：
Chen Y;Wang Y;Xuan Z;Chen M;Zhang MQ
摘要 定义染色质相互作用频率和拓扑结构域是基因组结构注释的巨大挑战。尽管染色体构象捕获（3C）及其衍生方法已被开发用于探索全局相互作用组，但它们受到高实验复杂性和成本的限制。在这里，我们描述了一种称为 CITD 的新型计算方法，用于通过整合组蛋白修饰数据来从头预测染色质相互作用图。我们利用来自人成纤维细胞IMR90细胞和胚胎干细胞（H1）的公开表观基因组数据来开发和测试CITD，它不仅可以成功重建Hi-C技术发现的染色质相互作用频率，还可以提供染色体组织的额外新颖细节。我们预测了来自 Roadmap Epigenomics 和 ENCODE 项目的 98 种其他细胞类型的染色质相互作用频率、拓扑结构域及其状态（例如活性或抑制）。总共 131 个蛋白质编码基因位于 100 种细胞类型中 78 个保留的边界附近，被发现在核小体组织和染色质组装的功能类别中显着丰富。 CITD 及其预测结果可用于补充从有限的 Hi-C 数据导出的拓扑域，并促进对染色体组织背后的空间原理的理解。
Abstract Defining chromatin interaction frequencies and topological domains is a great challenge for the annotations of genome structures. Although the chromosome conformation capture (3C) and its derivative methods have been developed for exploring the global interactome, they are limited by high experimental complexity and costs. Here we describe a novel computational method, called CITD, for de novo prediction of the chromatin interaction map by integrating histone modification data. We used the public epigenomic data from human fibroblast IMR90 cell and embryonic stem cell (H1) to develop and test CITD, which can not only successfully reconstruct the chromatin interaction frequencies discovered by the Hi-C technology, but also provide additional novel details of chromosomal organizations. We predicted the chromatin interaction frequencies, topological domains and their states (e.g. active or repressive) for 98 additional cell types from Roadmap Epigenomics and ENCODE projects. A total of 131 protein-coding genes located near 78 preserved boundaries among 100 cell types are found to be significantly enriched in functional categories of the nucleosome organization and chromatin assembly. CITD and its predicted results can be used for complementing the topological domains derived from limited Hi-C data and facilitating the understanding of spatial principles underlying the chromosomal organization.