IDENTIFICATION OF SHORTENED 3′ UNTRANSLATED REGIONS FROM EXPRESSION ARRAYS

摘要

Cancer cells have been recently shown to express high level of short 3′UTR isoforms that can escape miRNA-mediated regulation. We present here a computational procedure for systematically identifying shortened 3′UTRs by Affymetrix 3′ microarrays. The advantage of this technology compared to more recent and promising ones such as exon arrays and RNA-Seq is that, giving the relatively small cost, already existing datasets in public databases include a considerably higher number of experiments. Moreover, the design of Affymetrix Gene Chips is well-suited for 3′UTR analysis of a large number of genes. Initially, Affymetrix individual probes are regrouped into customized probesets mapping specifically the CDS or the 3′UTR of the transcript, according to RefSeq annotation. Then, candidate 3′UTR shortening events are identified by statistical differential expression analysis of customized probesets in different biological conditions. The procedure has been applied to expression data from two ovarian adenocarcinoma datasets. Selected gene sets are significantly enriched for annotated splice variant genes as well as genes involved in estrogen dependent cancer mechanisms, confirming the validity of the proposed procedure.