新型系统生物学与肿瘤血管新生药物靶标建模

项目名称： 新型系统生物学与肿瘤血管新生药物靶标建模

项目编号： No.60871100

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 王琳

作者单位： 北京邮电大学

项目金额： 28万元

中文摘要： 基于线性规划和分解过程，结合Kappa统计和模糊启发式聚类的构建单分子网络的基础上提出了构建中心分子中心功能聚类知识网络。主要工作是：基于结合分解过程和Kappa统计的显著性单分子网络构建与分析。基于重要功能聚类和推断分析的早期大肠癌中的FOS增殖网络构建，目的是建立显著性单分子网络。基于生物计算的通过对照人体正常邻近组织的肺腺癌中分泌磷蛋白1的上游入侵网络构建及分析；无肿瘤肝炎/肝硬化组织和人类肝细胞癌转化中的基于细胞周期功能细胞周期蛋白依赖性激酶抑制剂3，基于分泌功能的AFP分子网络，基于磷蛋白功能RRM2分子网络，基于细胞周期功能的生存素分子网络构建。基于生物计算的脑性艾滋病患者和其对照组病人中的MYBPC1分子磷蛋白网络，CREB5分子调节网络，TNFRSF11B分子发育网络构建与分析。基于生物计算的黑猩猩和人类左脑中糖原脱支酶6，烯醇化酶超族成员1, 外核苷酸焦磷酸酶/磷酸二酯酶2, 谷胱甘肽S-转移酶μ#21644;a-甘露糖苷酶2代谢网络分析。研究出中心分子的中心功能模块与疾病知识点如肝癌入侵，增殖等之间的密切联系，对疾病的诊断和治疗及鉴别潜在的新治疗靶标基因具有更加深远的指导意义

中文关键词： 显著性差异分子；分子网络；DAVID功能聚类；肿瘤；脑

英文摘要： Based on integrated gene regulatory network infer method by linear programming and a decomposition procedure with analysis of the significant function cluster using kappa statistics and fuzzy heuristic clustering from the database for annotation visualization and integrated discovery, we constructed and analyzed significant higher expression gene AFP, RRM2, NUSAP1, ACTN2 activated & inhibited functional network from HCC vs no-tumor hepatitis/cirrhosis pateints in GEO Dataset. We have successfully applied this method to gene data analysis, and made breakthroughs in our studies of AFP secreted network, RRM2 phosphoprotein network in HCC and TNFRSF11B development network, CREB5 regulation network, MYBPC1 phosphoprotein network and IFI27 network in frontal cortex of HIV encephalitis. Our study proved that in AFP secreted network, we gained negative result of AFP secreted module and predicted decrease of AFP secreted module in HCC. Importantly, we datamined that AFP secreted cluster of HCC was involved in disease mutation (only in experiment) without cell surface receptor linked signal transduction, neuroactive ligand-receptor interaction, cell-cell signaling and pancreas (only in control), the condition was vital to invasion of HCC. Our result revealed that common terms in both control and experiment included secreted, extracellular region, extracellular region part, extracellular space, signal peptide, signal, disulfide bond, glycosylation site: N-linked (GlcNAc...) and glycoprotein, and these terms were less relative to invasion, therefore we deduced weaker AFP secreted network in HCC. In RRM2 phosphoprotein network, we obtained negative result of RRM2 phosphoprotein module and predicted decrease of RRM2 phosphoprotein module in HCC. Otherwise, our integrative result showed that RRM2 phosphoprotein of HCC contained common terms of phosphoprotein and cell cycle, particular terms of cell-cell signaling, cell projection part, glycoprotein, cell projection, cell adhesion, biological adhesion, integral to plasma membrane, plasma membrane, kinase and phosphorus metabolic process, and no terms of cell death and ion binding compared with no-tumor hepatitis/cirrhotic liver tissues, all the condition was vital to invasion of HCC. Therefore, we deduced weaker RRM2 phosphoprotein function in HCC. In NUSAP1 cell cycle network, we acquired positive result of NUSAP1 cell cycle module and predicted increase of NUSAP1 cell cycle module in HCC. We datamined that NUSAP1 cell cycle cluster of HCC was involved in cell cycle checkpoint and regulation of phosphorylation (only in experiment) without disease mutation and transcription (only in control), the condition was vital to proliferation of HCC. Our result demonstrated that common terms in both control and experiment included cell cycle, phosphoprotein, intracellular non-membrane-bounded organelle, acetylation and ubl conjugation, and these terms were more relative to proliferation, therefore we deduced stronger NUSAP1 cell cycle network in HCC. In ACTN2 non-membrane-bounded organelle network, we got negative result of ACTN2 non-membrane-bounded organelle module and predicted decrease of ACTN2 non-membrane-bounded organelle module in HCC. ACTN2 non-membrane-bounded organelle cluster of HCC was involved in positive regulation of cell cycle, DNA damage and phosphorus metabolic process (only in experiment) without plasma membrane (only in control), the condition was vital to proliferation and cell death of HCC.

英文关键词： significant expressed molecules; computational network construction; DAVID gene functional classification; cancer; brian