识别拓扑关联域(TAD),它们被认为是染色体结构和功能的基本单位,可以促进染色体3D结构的探索。已经提出了通过检测TAD的边界或将紧密交互的区域识别为TAD来识别TAD的方法。虽然很少研究TAD的可能内部结构。在这项研究中,我们假设TAD由核心及其周围的附件组成,并提出了一种方法,名为CATAD,基于核心-依附结构模型识别TAD。在CATAD,基于局部密度和余弦相似性识别TAD的核心,和周围的附件是基于边界绝缘确定。CATAD应用于两种人类细胞系和两种小鼠细胞系的Hi-C数据,结果表明,通过CATAD鉴定的TAD的边界被结构蛋白显着富集,组蛋白修饰,转录起始位点和酶。此外,在许多情况下,CATAD优于其他方法,就平均峰值而言,边界标记比率和倍数变化。此外,CATAD是健壮的,很少受到Hi-C矩阵的不同分辨率的影响。最后,基于核心附件结构识别TAD是有用的,这可能会启发研究人员从可能的空间结构和形成过程的角度探索TAD。
Identifying topologically associating domains (TADs), which are considered as the basic units of chromosome structure and function, can facilitate the exploration of the 3D-structure of chromosomes. Methods have been proposed to identify TADs by detecting the boundaries of TADs or identifying the closely interacted regions as TADs, while the possible inner structure of TADs is seldom investigated. In this study, we assume that a TAD is composed of a core and its surrounding attachments, and propose a method, named CATAD, to identify TADs based on the core-attachment structure model. In CATAD, the cores of TADs are identified based on the local density and cosine similarity, and the surrounding attachments are determined based on boundary insulation. CATAD was applied to the Hi-C data of two human cell lines and two mouse cell lines, and the results show that the boundaries of TADs identified by CATAD are significantly enriched by structural proteins, histone modifications, transcription start sites and enzymes. Furthermore, CATAD outperforms other methods in many cases, in terms of the average peak, boundary tagged ratio and fold change. In addition, CATAD is robust and rarely affected by the different resolutions of Hi-C matrices. Conclusively, identifying TADs based on the core-attachment structure is useful, which may inspire researchers to explore TADs from the angles of possible spatial structures and formation process.