Gan Yanglan, Li Ning, Xin Yongchang, Zou Guobing
School of Computer Science and Technology, Donghua University, Shanghai, China.
School of Computer Engineering and Science, Shanghai University, Shanghai, China.
Front Genet. 2020 Jan 15;10:1298. doi: 10.3389/fgene.2019.01298. eCollection 2019.
Epigenetic alteration is a fundamental characteristic of nearly all human cancers. Tumor cells not only harbor genetic alterations, but also are regulated by diverse epigenetic modifications. Identification of epigenetic similarities across different cancer types is beneficial for the discovery of treatments that can be extended to different cancers. Nowadays, abundant epigenetic modification profiles have provided a great opportunity to achieve this goal. Here, we proposed a new approach TriPCE, introducing tri-clustering strategy to integrative pan-cancer epigenomic analysis. The method is able to identify coherent patterns of various epigenetic modifications across different cancer types. To validate its capability, we applied the proposed TriPCE to analyze six important epigenetic marks among seven cancer types, and identified significant cross-cancer epigenetic similarities. These results suggest that specific epigenetic patterns indeed exist among these investigated cancers. Furthermore, the gene functional analysis performed on the associated gene sets demonstrates strong relevance with cancer development and reveals consistent risk tendency among these investigated cancer types.
表观遗传改变是几乎所有人类癌症的一个基本特征。肿瘤细胞不仅存在基因改变，还受到多种表观遗传修饰的调控。识别不同癌症类型之间的表观遗传相似性，有利于发现可应用于不同癌症的治疗方法。如今，丰富的表观遗传修饰图谱为实现这一目标提供了绝佳机会。在此，我们提出了一种新方法TriPCE，将三聚类策略引入泛癌表观基因组综合分析。该方法能够识别不同癌症类型中各种表观遗传修饰的连贯模式。为验证其能力，我们应用所提出的TriPCE分析了七种癌症类型中的六种重要表观遗传标记，并确定了显著的跨癌表观遗传相似性。这些结果表明，在这些研究的癌症中确实存在特定的表观遗传模式。此外，对相关基因集进行的基因功能分析表明，其与癌症发展密切相关，并揭示了这些研究的癌症类型之间一致的风险倾向。
