Creighton Chad J, Nagaraja Ankur K, Hanash Samir M, Matzuk Martin M, Gunaratne Preethi H
The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
RNA. 2008 Nov;14(11):2290-6. doi: 10.1261/rna.1188208. Epub 2008 Sep 23.
MicroRNAs are short (approximately 22 nucleotides) noncoding RNAs that regulate the stability and translation of mRNA targets. A number of computational algorithms have been developed to help predict which microRNAs are likely to regulate which genes. Gene expression profiling of biological systems where microRNAs might be active can yield hundreds of differentially expressed genes. The commonly used public microRNA target prediction databases facilitate gene-by-gene searches. However, integration of microRNA-mRNA target predictions with gene expression data on a large scale using these databases is currently cumbersome and time consuming for many researchers. We have developed a desktop software application which, for a given target prediction database, retrieves all microRNA:mRNA functional pairs represented by an experimentally derived set of genes. Furthermore, for each microRNA, the software computes an enrichment statistic for overrepresentation of predicted targets within the gene set, which could help to implicate roles for specific microRNAs and microRNA-regulated genes in the system under study. Currently, the software supports searching of results from PicTar, TargetScan, and miRanda algorithms. In addition, the software can accept any user-defined set of gene-to-class associations for searching, which can include the results of other target prediction algorithms, as well as gene annotation or gene-to-pathway associations. A search (using our software) of genes transcriptionally regulated in vitro by estrogen in breast cancer uncovered numerous targeting associations for specific microRNAs-above what could be observed in randomly generated gene lists-suggesting a role for microRNAs in mediating the estrogen response. The software and Excel VBA source code are freely available at http://sigterms.sourceforge.net.
微小RNA是短的（约22个核苷酸）非编码RNA，可调节mRNA靶标的稳定性和翻译。已经开发了许多计算算法来帮助预测哪些微小RNA可能调节哪些基因。对微小RNA可能活跃的生物系统进行基因表达谱分析可产生数百个差异表达基因。常用的公共微小RNA靶标预测数据库便于逐个基因搜索。然而，对于许多研究人员来说，使用这些数据库将微小RNA-mRNA靶标预测与大规模基因表达数据整合目前既繁琐又耗时。我们开发了一个桌面软件应用程序，对于给定的靶标预测数据库，该程序可检索由一组实验得出的基因所代表的所有微小RNA：mRNA功能对。此外，对于每个微小RNA，该软件会计算基因集中预测靶标的过度富集统计量，这有助于揭示特定微小RNA和微小RNA调节基因在研究系统中的作用。目前，该软件支持搜索来自PicTar、TargetScan和miRanda算法的结果。此外，该软件可以接受任何用户定义的基因与类别关联集进行搜索，其中可以包括其他靶标预测算法的结果，以及基因注释或基因与通路的关联。使用我们的软件对乳腺癌中受雌激素体外转录调控的基因进行搜索，发现了特定微小RNA的大量靶向关联——比在随机生成的基因列表中观察到的要多——这表明微小RNA在介导雌激素反应中发挥作用。该软件和Excel VBA源代码可从http://sigterms.sourceforge.net免费获取。
