antagonism pattern detection between microrna and target expression in ewing’s sarcomamicrorna表达和目标之间的对立模式检测尤文氏肉瘤.pdfVIP

Antagonism Pattern Detection between MicroRNA and Target Expression in Ewing’s Sarcoma 1,2,3 1,4 1,4 5 ´ 5 Loredana Martignetti *, Karine Laud-Duval , Franck Tirode , Gaelle Pierron , Stephanie Reynaud , Emmanuel Barillot1,2,3, Olivier Delattre1,4, Andrei Zinovyev 1,2,3 1 Institut Curie, Paris, France, 2 INSERM U900, Paris, France, 3 Mines ParisTech, Fontainebleau, France, 4 INSERM U830, Paris, France, 5 Department of Tumor Biology, Institut Curie Hospital, Paris, France Abstract MicroRNAs (miRNAs) have emerged as fundamental regulators that silence gene expression at the post-transcriptional and translational levels. The identification of their targets is a major challenge to elucidate the regulated biological processes. The overall effect of miRNA is reflected on target mRNA expression, suggesting the design of new investigative methods based on high-throughput experimental data such as miRNA and transcriptome profiles. We propose a novel statistical measure of non-linear dependence between miRNA and mRNA expression, in order to infer miRNA-target interactions. This approach, which we name antagonism pattern detection, is based on the statistical recognition of a triangular-shaped pattern in miRNA-target expression profiles. This pattern is observed in miRNA-target expression measurements since their simultaneously elevated expression is statistically under-represented in the case of miRNA silencing effect. The proposed method enables miRNA target prediction to strongly rely on cellular context and physiological conditions reflected by expression data. The procedure has been assessed on synthetic datasets and tested on a set of real positive cont