基于全基因组测序建立病毒拷贝数和整合位点的生物信息学方法及数据分析

Viral integration is a physiological process when a virus infects the host cell. During the process, viral DNA inserts itself into the host cell and participates in its DNA replication. This can help it to escape immunosurveillance and maintain self-survival. The integration of oncogenic virus can transform or induce normal host cell into malignant tumor cell. Our lab has sequenced 10 cases of lymphocytic leukemia patients on their tumor tissue and paired normal tissue. Based on these data, we have developed a software, which is well-structured and easy to use, then use it to complete viral integration analysis efficiently, and finally found the high-frequency integration sites and global distribution of the virus. Our project will continue to complete the existing algorithm and pipeline. We will cooperate with clinicians, expand the sample size, gather more information about other kinds of oncogenic virus. With these data, we will build a database which contains high-frequency integration sites and global distribution of most oncogenic virus. Some important sites will be verified through experimental methods. It can predict or explore the mechanism of oncogenic virus integration and its carcinogenic effects. This study will help to clinical treatment and improve long-term survival of the patients.

病毒整合是病毒在感染宿主细胞过程中，将自身DNA插入到宿主细胞DNA中并参与其复制，以逃避宿主细胞免疫功能清除，维系自我生存等一系列生理过程。其中瘤性DNA病毒的整合，常会使宿主细胞发生转化，诱导或参与形成恶性肿瘤。本实验室测序了10例淋巴细胞瘤患者全基因组肿瘤和正常的配对数据，基于这些数据，已初步研发出一款可便于使用、结果准确、且可用于多种致瘤病毒整合分析的软件，大致找出病毒在人基因组上高频整合位点及整体分布规律。本项目将继续完善开发本实验室已有的病毒整合软件算法及分析流程，和临床医生合作，扩大分析样本，整合多种致瘤性病毒信息，构建致瘤性病毒高频整合位点和整合规律分布数据库，以及部分病毒整合功能验证，探索致瘤性病毒人体整合的机理及其致癌影响，进而为临床治疗提供帮助，改善致瘤性病毒引起疾病相关患者的长期生存。

我们开发了病毒整合分析包 (QAP)，用于解决与从大量病毒种群测序数据中进行生物学解释相关的问题。 QAP 通过首先引入“病毒 OTU”的定义来提供对病毒生态学的定量洞察，并支持广泛的病毒群落分析和结果可视化。 考虑到更广泛的用户，开发了各种形式的 QAP，包括命令行、图形用户界面和 Web 服务器。.我们将此方法应用于 EBV 整合位点检测，并在 Natural Killer T 患者中找到有意义的结果。