Corticosteroid-regulated genes in rat kidney: mining time series array data
Corticosteroid-regulated genes in rat kidney: mining time series array data
复制标题
DOI：
10.1152/ajpendo.00196.2005
复制
发表时间：
2005-11-01
影响因子：
5.1
通讯作者：
Jusko, WJ
中科院分区：
文献类型：
--
作者：
Almon, RR;Lai, W;Jusko, WJ
肾脏是皮质类固醇相关不良反应的主要靶点。一个微阵列数据集的产生，以检查在大鼠肾脏中的基因表达的变化，甲基强的松龙。给药后16次处死4只对照组动物和48只给药组动物。肾脏RNA用于查询52个单独的Affyssin芯片，为每个芯片生成15，967个不同探针组的数据。适用于时间序列数据的挖掘技术，确定药物调控的基因表达的变化。四个连续过滤器消除了在组织中不表达、不受药物调节或不符合规定的质量控制标准的探针组。这些过滤器排除了14，890个探针组（94%）。合理选择滤波器是时间序列数据挖掘的有效工具。剩余的数据可以通过聚类和数学建模进行进一步分析。对该过滤数据集的初步分析确定了一组基因，其调控模式与原型皮质类固醇增强基因高度相关。分析该组中的20个基因以及显示下调或无调节的选定基因的跨物种保守的5'GRE半位点。在一般情况下，结果支持的假设，即保守的DNA结合位点的存在可以作为一个重要的辅助纯分析方法聚类基因到具有共同的调控机制的群体。该数据集以及肝脏和肌肉的类似数据集可以在线获得，其格式适合其他人进行进一步分析。
Kidney is a major target for adverse effects associated with corticosteroids. A microarray dataset was generated to examine changes in gene expression in rat kidney in response to methylprednisolone. Four control and 48 drug-treated animals were killed at 16 times after drug administration. Kidney RNA was used to query 52 individual Affymetrix chips, generating data for 15,967 different probe sets for each chip. Mining techniques applicable to time series data that identify drug-regulated changes in gene expression were applied. Four sequential filters eliminated probe sets that were not expressed in the tissue, not regulated by drug, or did not meet defined quality control standards. These filters eliminated 14,890 probe sets (94%) from further consideration. Application of judiciously chosen filters is an effective tool for data mining of time series datasets. The remaining data can then be further analyzed by clustering and mathematical modeling. Initial analysis of this filtered dataset identified a group of genes whose pattern of regulation was highly correlated with prototype corticosteroid enhanced genes. Twenty genes in this group, as well as selected genes exhibiting either downregulation or no regulation, were analyzed for 5' GRE half-sites conserved across species. In general, the results support the hypothesis that the existence of conserved DNA binding sites can serve as an important adjunct to purely analytic approaches to clustering genes into groups with common mechanisms of regulation. This dataset, as well as similar datasets on liver and muscle, are available online in a format amenable to further analysis by others.