removal of au bias from microarray mrna expression data enhances computational identification of active micrornas删除非盟偏见从微阵列mrna表达数据增强了计算活性小分子核糖核酸的识别.pdfVIP

Removal of AU Bias from Microarray mRNA Expression Data Enhances Computational Identification of Active MicroRNAs Ran Elkon, Reuven Agami* Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands Abstract Elucidation of regulatory roles played by microRNAs (miRs) in various biological networks is one of the greatest challenges of present molecular and computational biology. The integrated analysis of gene expression data and 39-UTR sequences holds great promise for being an effective means to systematically delineate active miRs in different biological processes. Applying such an integrated analysis, we uncovered a striking relationship between 39-UTR AU content and gene response in numerous microarray datasets. We show that this relationship is secondary to a general bias that links gene response and probe AU content and reflects the fact that in the majority of current arrays probes are selected from target transcript 39- UTRs. Therefore, removal of this bias, which is in order in any analysis of microarray datasets, is of crucial importance when integrating expression data and 39-UTR sequences to identify regulatory elements embedded in this region. We developed visualization and normalization schemes for the detection and removal of such AU biases and demonstrate that their application to microarray data significantly enhances the computational identification of active miRs. Our results substantiate that, after removal of AU biases, mRNA expression profiles contain ample information which allows in silico detection of miRs that are active in physiological conditions. Citation: Elkon R, Agami R (2008) Removal of AU Bias from Microarray mRNA Expression Data Enhances Computational Identification of Active MicroRNAs. PLoS Comput Biol 4(10): e1000189. doi:10.1371/journal.pcbi.1000189 Edito