Ochsner Scott A, Steffen David L, Hilsenbeck Susan G, Chen Edward S, Watkins Christopher, McKenna Neil J
Department of Molecular and Cellular Biology, Nuclear Receptor Signaling Atlas Bioinformatics Resource, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Cancer Res. 2009 Jan 1;69(1):23-6. doi: 10.1158/0008-5472.CAN-08-3492.
With large amounts of public expression microrray data being generated by multiple laboratories, it is a significant task for the bench researcher to routinely identify available datasets, and then to evaluate the collective evidence across these datasets for regulation of a specific gene in a given system. 17beta-Estradiol stimulation of MCF-7 cells is a widely used model in the growth of breast cancer. Although myriad independent studies have profiled the global effects of this hormone on gene expression in these cells, disparate experimental variables and the limited power of the individual studies have combined to restrict the agreement between them as to the specific gene expression signature elicited by this hormone. To address these issues, we have developed a freely accessible Web resource, Gene Expression MetaSignatures (GEMS) that provides the user a consensus for each gene in the system. We conducted a weighted meta-analysis encompassing over 13,000 genes across 10 independent published datasets addressing the effect of 17beta-estradiol on MCF-7 cells at early (3-4 hours) and late (24 hours) time points. In a literature survey of 58 genes previously shown to be regulated by 17beta-estradiol in MCF-7 cells, the meta-analysis combined the statistical power of the underlying datasets to call regulation of these genes with nearly 85% accuracy (false discovery rate-corrected P < 0.05). We anticipate that with future expression microarray dataset contributions from investigators, GEMS will evolve into an important resource for the cancer and nuclear receptor signaling communities.
随着多个实验室生成大量的公共表达微阵列数据,对于实验研究人员来说,定期识别可用数据集,然后评估这些数据集关于特定系统中特定基因调控的综合证据是一项重要任务。17β-雌二醇刺激MCF-7细胞是乳腺癌生长中广泛使用的模型。尽管众多独立研究已分析了这种激素对这些细胞中基因表达的整体影响,但不同的实验变量和单个研究的有限效力共同限制了它们在这种激素引发的特定基因表达特征方面的一致性。为了解决这些问题,我们开发了一个可免费访问的网络资源——基因表达元特征(GEMS),它为系统中的每个基因提供了一个共识。我们进行了一项加权荟萃分析,涵盖了10个独立发表的数据集中的13000多个基因,这些数据集研究了17β-雌二醇在早期(3 - 4小时)和晚期(24小时)时间点对MCF-7细胞的影响。在对先前显示在MCF-7细胞中受17β-雌二醇调控的58个基因的文献调查中,荟萃分析结合了基础数据集的统计效力,以近85%的准确率(经错误发现率校正的P < 0.05)判定这些基因的调控情况。我们预计,随着研究人员未来贡献更多的表达微阵列数据集,GEMS将发展成为癌症和核受体信号传导领域的重要资源。