Topologically associating domains (TADs) have emerged as basic structural and functional units of genome organization and have been determined by many computational methods from Hi-C contact maps. However, the TADs obtained by different methods vary greatly, which makes the accurate determination of TADs a challenging issue and hinders subsequent biological analyses about their organization and functions. Obvious inconsistencies among the TADs identified by different methods indeed make the statistical and biological properties of TADs overly depend on the chosen method rather than on the data. To this end, we use the consensus structural information captured by these methods to define the TAD separation landscape for decoding the consensus domain organization of the 3D genome. We show that the TAD separation landscape could be used to compare domain boundaries across multiple cell types for discovering conserved and divergent topological structures, decipher three types of boundary regions with diverse biological features, and identify consensus TADs (ConsTADs). We illustrate that these analyses could deepen our understanding of the relationships between the topological domains and chromatin states, gene expression, and DNA replication timing.

中文翻译：

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定义拓扑域的分离景观以解码 3D 基因组的共识域组织

拓扑关联域 (TAD) 已成为基因组组织的基本结构和功能单元，并通过 Hi-C 接触图的许多计算方法确定。然而，不同方法获得的TAD差异很大，这使得TAD的准确测定成为一个具有挑战性的问题，并阻碍了后续对其组织和功能的生物学分析。不同方法鉴定的 TAD 之间明显的不一致确实使得 TAD 的统计和生物学特性过度依赖于所选择的方法而不是数据。为此，我们使用这些方法捕获的共有结构信息来定义 TAD 分离景观，以解码 3D 基因组的共有域组织。我们表明，TAD 分离景观可用于比较多种细胞类型的域边界，以发现保守和发散的拓扑结构，破译具有不同生物学特征的三种类型的边界区域，并识别共有 TAD (ConsTAD)。我们说明这些分析可以加深我们对拓扑结构域和染色质状态、基因表达和 DNA 复制时间之间关系的理解。