A computational method to predict topologically associating domain boundaries combining histone Marks and sequence information
A computational method to predict topologically associating domain boundaries combining histone Marks and sequence information
复制标题
结合组蛋白标记和序列信息预测拓扑关联域边界的计算方法
DOI：
10.1186/s12864-019-6303-z
复制
发表时间：
2019-12-27
期刊：
影响因子：
4.4
通讯作者：
Li, Meng Long
中科院分区：
文献类型：
--
作者：
Gan, Wei;Luo, Juan;Li, Meng Long
背景染色质的三维结构在细胞分化和发育过程中起着重要作用。Hi-C和其他基于3C的技术使我们能够深入研究染色质结构。许多研究表明，拓扑关联结构域（topologically associated domains，简称ATD）作为结构和功能单位，在不同的器官中是保守的。然而，我们的理解的潜在机制的的边界formation.ResultsWe开发了一种计算方法，TAD-Lactuca，推断这种结构，通过采取上下文信息的表观遗传修饰信号和基因组上的主要DNA序列信息。TAD-Lactuca在多分辨率和不同数据集的情况下稳定。它可以实现高准确性，甚至优于国家的最先进的方法时，序列模式纳入。此外，几个转录因子结合基序，除了众所周知的CCCTC结合因子（CTCF）基序，被发现显着丰富的boundars.ConclusionsWe提供了一个低成本，有效的方法来预测边界。上述结果表明，序列特征的引入可以显着提高性能。序列模体富集分析表明，在染色质折叠的边界附近存在多个基因调控模体，这与TADs可能作为基因调控的功能单元相一致，并暗示序列模式在染色质折叠中具有重要作用。
BackgroundThe three-dimensional (3D) structure of chromatins plays significant roles during cell differentiation and development. Hi-C and other 3C-based technologies allow us to look deep into the chromatin architectures. Many studies have suggested that topologically associating domains (TAD), as the structure and functional unit, are conserved across different organs. However, our understanding about the underlying mechanism of the TAD boundary formation is still limited.ResultsWe developed a computational method, TAD–Lactuca, to infer this structure by taking the contextual information of the epigenetic modification signals and the primary DNA sequence information on the genome. TAD–Lactuca is found stable in the case of multi-resolutions and different datasets. It could achieve high accuracy and even outperforms the state-of-art methods when the sequence patterns were incorporated. Moreover, several transcript factor binding motifs, besides the well-known CCCTC-binding factor (CTCF) motif, were found significantly enriched on the boundaries.ConclusionsWe provided a low cost, effective method to predict TAD boundaries. Above results suggested the incorporation of sequence features could significantly improve the performance. The sequence motif enrichment analysis indicates several gene regulation motifs around the boundaries, which is consistent with TADs may serve as the functional units of gene regulation and implies the sequence patterns would be important in chromatin folding.