用系统生物学方法对肺癌发生基因调控网络的研究

项目名称： 用系统生物学方法对肺癌发生基因调控网络的研究

项目编号： No.91229105

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 王俊文

作者单位： 香港大学深圳研究院

项目金额： 90万元

中文摘要： 肺癌是中国及全世界发病及致死率最高的癌症之一。目前中国每年新增肺癌病例有近60万，患者的五年生存率很低，只有15%左右，这给病人和家庭带来很大的经济及精神负担。了解并掌握肺癌形成及转化的调控网络，以此进行早期诊断及有效治疗是目前肺癌研究的焦点。尽管已有大量研究，但肺癌的调控机理还不清楚。我们近期开发的ChIP-Array平台，可对染色质免疫沉淀-测序和基因表达谱数据进行组合分析，从而构建以单个转录因子为中心的调控网络。我们组成了一个以临床转化医学和系统生物学为核心的国际团队，将对肺癌的关键转录因子的结合位点进行全基因组定位，并拓展ChIP-Array平台来构建以多个转录因子为中心的调控网络。我们也将开发一系列关于调控网络构建及调控模块查询的算法和软件，并创建肺癌基因调控网络与模块数据库。该研究将可找到肺癌形成及转化新的调控网络及模块，为癌症研究提供理论基础，并为药物开发提供新靶点。

中文关键词： 肺癌；转录调控网络；染色质免疫共沉淀；；

英文摘要： Lung cancer is one of the cancers with the highest incidence and mortality in China and worldwide. There are about 600 thousand new lung cancers per year in China, with an overall 5-year survival rate of only 15%, which causes huge financial and psychological burdens to the patient, the family and the society. Understanding the regulatory networks of lung cancer pathogenesis and transformation is becoming a key topic in the field. Large amount of scientific research have been conducted in this area, however, the underlying mechanism for lung cancer pathogenesis is still not well known. We have recently developed a web server, ChIP-Array, to construct a transcription factor (TF) centered regulatory network based on combinatory analysis of gene expression array data and Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data. In this project, we have formed an international team of translational medicine and systems biology to tackle this problem. We will use ChIP-seq technology to map the transcription factor binding sites (TFBS) of the key transcription factors involving in lung cancer, and extend our ChIP-Array tool to construct multi-TF centered regulatory network. We will further develop algorithm and software tools to construct network and search network modules, and build a data

英文关键词： lung cancer；regulatory networks；ChIP-seq；；