TADKB: Family classification and a knowledge base of topologically associating domains
TADKB: Family classification and a knowledge base of topologically associating domains
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DOI：
10.1186/s12864-019-5551-2
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发表时间：
2019-03-14
期刊：
影响因子：
4.4
通讯作者：
Wang, Zheng
中科院分区：
文献类型：
--
作者：
Liu, Tong;Porter, Jacob;Wang, Zheng
研究背景拓扑关联结构域（Topologically associated domains，TADs）被认为是基因组的结构和功能单位。然而，在文献中，研究人员可以获得家庭分类和详细的信息TADs.ResultsWe建立了一个在线知识库TADKB集成知识TADs在elevencell类型的人类和小鼠的TADs缺乏一个综合资源。TADKB提供了每一条染色体和TADs的预测三维结构，以及每一条染色体中存在的蛋白质编码基因和长链非编码RNA（lncRNA）的详细注释。除了由群体Hi-C推断的3D染色体结构之外，17个GM 12878细胞的单细胞单倍型分辨的染色体3D结构也整合在TADKB中。用户可以提交查询基因/lncRNA ID/序列以搜索包含查询基因或lncRNA的序列。我们还将TAD分类为家族。为了实现这一点，我们使用重建的3D结构的TADs之间的TM分数作为结构相似性和皮尔逊的相关系数之间的倍数丰富的染色质状态作为功能相似性。基于结构和功能的相似性，分别使用谱聚类算法与各种预定义数目的聚类对一种细胞类型中的所有TAD进行聚类。我们计算了结构簇和功能簇的TADs，发现在染色质状态耗尽的功能簇中，大多数TADs聚集在一个或两个结构簇中。这一新的发现表明TADs的3D结构和它们的DNA功能之间的连接在染色质states.ConclusionTADKB可在http://dna.cs.miami.edu/TADKB/。
BackgroundTopologically associating domains (TADs) are considered the structural and functional units of the genome. However, there is a lack of an integrated resource for TADs in the literature where researchers can obtain family classifications and detailed information about TADs.ResultsWe built an online knowledge base TADKB integrating knowledge for TADs in elevencell types of human and mouse. For each TAD, TADKB provides the predicted three-dimensional (3D) structures of chromosomes and TADs, and detailed annotations about the protein-coding genes and long non-coding RNAs (lncRNAs) existent in each TAD. Besides the 3D chromosomal structures inferred by population Hi-C, the single-cell haplotype-resolved chromosomal 3D structures of 17 GM12878 cells are also integrated in TADKB. A user can submit query gene/lncRNA ID/sequence to search for the TAD(s) that contain(s) the query gene or lncRNA. We also classified TADs into families. To achieve that, we used the TM-scores between reconstructed 3D structures of TADs as structural similarities and the Pearson's correlation coefficients between the fold enrichment of chromatin states as functional similarities. All of the TADs in one cell type were clustered based on structural and functional similarities respectively using the spectral clustering algorithm with various predefined numbers of clusters. We havecompared the overlapping TADs from structural and functional clusters and found that most of the TADs in the functional clusters with depleted chromatin states are clustered into one or two structural clusters. This novel finding indicates a connection between the 3D structures of TADs and their DNA functions in terms of chromatin states.ConclusionTADKB is available at http://dna.cs.miami.edu/TADKB/.