我国80%的原发性肝癌病人伴有乙肝病毒（HBV）感染。已有研究发现HBV病毒突变与肝癌发生高度相关，然而其致癌机制仍不明确。我们之前的研究与前期工作分析了上万例HBV病毒基因组突变序列的公共数据和数千例HBV病毒基因组的自身测序数据，确定了HBV病毒从慢性感染到肝癌发生的特征性热点突变，并且发现HBV病毒致癌机制具有中国人群的特异性。本项目拟采用基因组学，分子对接和分子动力学模拟等生物信息学方法系统地梳理中国人群HBV病毒导致肝癌发生的热点突变，着重从HBV病毒突变与宿主基因组共进化机制和HBV病毒突变导致免疫逃逸机制两个方面，来阐明其致癌机制，并使用实验手段验证关键突变。本项目拟构建公共数据库，将研究发现及建立的生物信息学工具与研究者共享。我们的研究将为HBV病毒相关肝癌的预防、早期诊断和治疗靶点选择，提供新的线索。

80% of our country's primary liver cancer patients with hepatitis B virus (HBV) infection. It has been found that HBV mutation is highly associated with the occurrence of liver cancer, but its carcinogenic mechanism remains unclear. Our previous research and preliminary work analyzed tens of thousands of public data on HBV virus mutations and our sequencing data for thousands of HBV virus genomes, identified characteristic hot-spot mutations in HBV viruses from chronic infection to liver cancer, and found the carcinogenic mechanism of HBV virus has the specificity of Chinese population. This project intends to use genomics and molecular docking and molecular dynamics bioinformatics methods to systematically sort out the hotspot mutations that cause HBV-induced liver cancer in Chinese populations, and to clarify the carcinogenic mechanism from the point of view of co-evolution of HBV mutations and host genomes and immune escape from HBV mutations. Experimental methods to verify key mutations. We shall to build up a public database to present the result of our research and bioinformatics tools for use by researchers. The project will provide new clues for the prevention, early diagnosis and treatment target selection of HBV-related liver cancer.