Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Nucleic Acids Res. 2019 Jan 8;47(D1):D1044-D1055. doi: 10.1093/nar/gky1139.
Whole-exome and whole-genome sequencing have revealed millions of somatic mutations associated with different human cancers, and the vast majority of them are located outside of coding sequences, making it challenging to directly interpret their functional effects. With the rapid advances in high-throughput sequencing technologies, genome-scale long-range chromatin interactions were detected, and distal target genes of regulatory elements were determined using three-dimensional (3D) chromatin looping. Herein, we present OncoBase (http://www.oncobase.biols.ac.cn/), an integrated database for annotating 81 385 242 somatic mutations in 68 cancer types from more than 120 cancer projects by exploring their roles in distal interactions between target genes and regulatory elements. OncoBase integrates local chromatin signatures, 3D chromatin interactions in different cell types and reconstruction of enhancer-target networks using state-of-the-art algorithms. It employs informative visualization tools to display the integrated local and 3D chromatin signatures and effects of somatic mutations on regulatory elements. Enhancer-promoter interactions estimated from chromatin interactions are integrated into a network diffusion system that quantitatively prioritizes somatic mutations and target genes from a large pool. Thus, OncoBase is a useful resource for the functional annotation of regulatory noncoding regions and systematically benchmarking the regulatory effects of embedded noncoding somatic mutations in human carcinogenesis.
全外显子组和全基因组测序揭示了数以百万计与不同人类癌症相关的体细胞突变，其中绝大多数位于编码序列之外，使得直接解释其功能效应具有挑战性。随着高通量测序技术的快速发展，检测到了基因组规模的长程染色质相互作用，并使用三维（3D）染色质环化确定了调控元件的远端靶基因。在此，我们展示了 OncoBase（http://www.oncobase.biols.ac.cn/），这是一个综合数据库，通过探索其在 68 种癌症类型的 120 多个癌症项目中 81385242 个体细胞突变在靶基因和调控元件之间的远端相互作用中的作用，对其进行注释。OncoBase 整合了局部染色质特征、不同细胞类型中的 3D 染色质相互作用以及使用最先进算法重建增强子-靶基因网络。它采用了信息丰富的可视化工具来显示整合的局部和 3D 染色质特征以及体细胞突变对调控元件的影响。从染色质相互作用中估计的增强子-启动子相互作用被整合到一个网络扩散系统中，该系统从大量的体细胞突变和靶基因中定量优先排序。因此，OncoBase 是对调控非编码区进行功能注释和系统地对人类致癌过程中嵌入的非编码体细胞突变的调控效应进行基准测试的有用资源。
