TopDom: an efficient and deterministic method for identifying topological domains in genomes.
TopDom: an efficient and deterministic method for identifying topological domains in genomes.
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DOI：
10.1093/nar/gkv1505
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发表时间：
2016-04-20
影响因子：
14.9
通讯作者：
Zhou XJ
中科院分区：
文献类型：
--
作者：
Shin H;Shi Y;Dai C;Tjong H;Gong K;Alber F;Zhou XJ
全基因组邻近连接检测能够以前所未有的分辨率识别染色质接触。多项研究表明，哺乳动物染色体由亚兆碱基分辨率的拓扑结构域 (TD) 组成，这些拓扑结构域似乎在不同细胞类型之间、在某种程度上甚至在生物体之间都是保守的。识别拓扑域现在是理解空间基因组组织的结构和功能的重要一步。然而，当前的 TD 识别方法需要大量的计算资源，需要仔细调整和/或遇到结果不一致的情况。在这项工作中，我们提出了一种高效且确定性的方法 TopDom 来识别 TD，以及一组用于评估其质量的统计方法。 TopDom 比现有方法高效得多，并且仅依赖于一个直观参数，即窗口大小，我们为此提供了易于实现的优化指南。与流行的方向索引算法相比，TopDom 还可以识别更多、更高质量的 TD。 TopDom 识别的 TD 为跨组织 TD 保护提供了强有力的支持。最后，我们的分析表明管家基因的位置与跨组织保守的 TD 密切相关。 TopDom的软件包和源代码可以在http://zhoulab.usc.edu/TopDom/获取。
Genome-wide proximity ligation assays allow the identification of chromatin contacts at unprecedented resolution. Several studies reveal that mammalian chromosomes are composed of topological domains (TDs) in sub-mega base resolution, which appear to be conserved across cell types and to some extent even between organisms. Identifying topological domains is now an important step toward understanding the structure and functions of spatial genome organization. However, current methods for TD identification demand extensive computational resources, require careful tuning and/or encounter inconsistencies in results. In this work, we propose an efficient and deterministic method, TopDom, to identify TDs, along with a set of statistical methods for evaluating their quality. TopDom is much more efficient than existing methods and depends on just one intuitive parameter, a window size, for which we provide easy-to-implement optimization guidelines. TopDom also identifies more and higher quality TDs than the popular directional index algorithm. The TDs identified by TopDom provide strong support for the cross-tissue TD conservation. Finally, our analysis reveals that the locations of housekeeping genes are closely associated with cross-tissue conserved TDs. The software package and source codes of TopDom are available at http://zhoulab.usc.edu/TopDom/.