Analysis of gene expression for apotosis using DNA chips

在过去几年中，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。许多研究人员研究了应激反应的表达谱，以了解应激反应的机制，如有毒化学物质或细胞因子。如果能够从这些数据中绘制出基因网络，我们就能够优先考虑目标基因，以开发代谢抑制剂、抗癌药物等药物化合物。因此，基因表达谱的分析和遗传网络的识别是非常重要的。在本研究中，进行了以下研究。(1)肿瘤细胞的应激反应采用12814个克隆组成的DNA芯片检测热休克后的基因表达。-在热休克后携带期诱导的两个基因簇中有41个基因。-基质金属蛋白酶3 （MMP-3）的表达在早期反应中明显增强。-研究了MMP-3抑制剂在热休克反应中的作用，发现MMP-3抑制剂可增强热休克诱导的细胞死亡。(2)细菌的胁迫反应为了探究有机溶剂耐受（OST）的生物学机制，采用DNA芯片技术采集了大肠杆菌的基因表达谱。通过对这些DNA芯片的分析，确定了一些基因是有机溶剂响应基因：半胱氨酸合成相关基因的上调表达被认为是还原能力增强的原因。(3)遗传互作分析我们提出了模糊自适应共振理论-二维矩阵（F2DMatrix）方法，从基因表达谱的时间历程数据推断遗传网络。利用实验时间序列数据，分析了酿酒酵母在二胺、热休克和H_2O_2氧化胁迫下的基因表达谱。经鉴定，热休克应力与Diamide的相互作用是两种应力的共同相互作用，KEGG图的命中率为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