The ComiR web-tool ready for an upgrade: the detection of new features to improve the prediction of microRNA targets

MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the translational repression and degradation of target mRNAs in the cell [1]. The RNA-induced silencing complexes (RISCs) include mature miRNAs used as templates to recognize the complementary mRNA targets. Several prediction tools are available to predict miRNA targets, however, only a small part of the interaction pairs has been validated by experimental approaches. In addition, none of these tools does take into account the network structure of miRNA-mRNA interactions, which involves collaborative and competition [2] effects that are crucial to efficiently predict the miRNA regulatory effects in a specific cellular context. A first solution to consider collaborative effects has been given by the web tool ComiR [3], which predicts the targets of a weighted set of miRNAs, provided the miRNA expression profile of the samples/tissues of interest. The analysis of the expression profile of the RNA fraction immunoprecipitated (IP) with the RISC proteins, namely Rip-Chip or Rip-Seq, has been widely used to detect which genes are regulated by the RISC machinery. Recently, we found that AGO2 and GW182 are associated with two distinct sets of mRNA characterized by different features [4]. One of the relevant features is the presence of putative miRNA binding sites in the coding region of the mRNA, in addition to the already widely explored involvement of the binding sites in the 3'UTR. Next, we tested whether ComiR would be improved by the introduction of such features