Analysis of gene expression for apotosis using DNA chips

近年来，DNA微阵列技术的快速发展使得在不同条件下同时测量数千个基因的表达水平成为可能。许多研究人员通过研究其表达谱来了解应激反应的机制，如有毒化学物质或细胞因子。如果能从这些数据中提取出基因网络，就能为代谢抑制剂、抗癌药物等药物的开发确定靶基因的优先顺序，因此基因表达谱的分析和基因网络的识别就显得尤为重要。在本研究中，进行了以下研究。(1)癌细胞的应激反应我们使用由12，814个克隆组成的DNA微阵列检测了热休克后的整体基因表达。- 在两个簇中有41个基因含有在热休克后的携带期被诱导的基因。- 基质金属蛋白酶3（MMP-3）的表达通过免疫组织化学方法检测。 关于我们 在早期的反应中得到了加强。我们研究了MMP-3抑制剂在热休克反应中的作用，发现MMP-3抑制剂增强了热休克诱导的细胞死亡。(2)细菌的应激反应为了探讨有机溶剂耐受性（OST）的生物学机制，利用基因芯片技术收集了大肠杆菌的基因表达谱。从这些DNA芯片的分析，一些基因被确定为有机溶剂的响应基因：半胱氨酸合成相关基因的表达上调被认为有助于增加的还原能力。(3)遗传相互作用分析我们发展了模糊自适应共振理论-二维矩阵（F2 DMatrix）方法，从基因表达谱的时程数据推断遗传网络。我们应用于实验时间序列数据，这是酿酒酵母的基因表达谱响应下的氧化应激，如二酰胺，热休克和H_2O_2。热激胁迫与二酰胺的相互作用是两种胁迫的共同作用，KEGG图谱的命中率为60%。少

Rapid advances in DNA microarray technologies over last several years have made it possible to measure the expression levels of thousands of genes simultaneously under different conditions. Many researchers have investigated the expression profiles to understand the mechanism of stress response, such as toxic chemicals or cytokines. If the genetic networks could be drawn from these data, we are able to prioritize target genes for development of medicinal compounds such as metabolic inhibiter, anticancer drug, and so on. Thus, the analysis of gene expression profiles and the identification of genetic networks are significantly important. In this research, the following studies were carried out.(1) Stress response of cancer cellsWe examined global gene expression after heat shock using DNA microarray consisting of 12,814 clones. -There were 41 genes in two clusters containing genes that were induced in the carry phase after heat shock. -Expression of matrix metalloproteinase 3 (MMP-3) wa … More s enhanced during the early response. -We investigated the role of MMP-3 inhibitor in the heat shock response, and found that the MMP-3 inhibitors enhanced heat shock-induced cell death.(2) Stress response of bacteriaIn order to investigate the biological mechanism for organic solvent tolerancy (OST), gene expression profiles of Escherichia coli were collected using DNA microarray. From the analysis of those DNA microarrays, some genes were identified as the organic solvent-responding genes : Up-regulated expression of the genes related to cysteine synthesis was considered to contribute to the increase of the reducing power.(3) Analysis of genetic interactionWe developed the fuzzy adaptive resonance theory - 2 dimensional matrix (F2DMatrix) method to infer genetic networks from time course data of gene expression profiles. We applied to experimental time series data, which are gene expression profiles of Saccharomyces cerevisiae responding under oxidative stresses such as Diamide, Heat Shock and H_2O_2. The identified interactions between Diamide and Heat Shock stress were confirmed to be the common interactions for two stresses, and the hit ratio was 60% for KEGG map. Less