MOTIVATION: PAR-CLIP, a CLIP-seq protocol, derives a transcriptome wide set of binding sites for RNA-binding proteins. Even though the protocol uses stringent washing to remove experimental noise, some of it remains. A recent study measured three sets of non-specific RNA backgrounds which are present in several PAR-CLIP datasets. However, a tool to identify the presence of common background in PAR-CLIP datasets is not yet available. RESULTS: We used the measured sets of non-specific RNA backgrounds to build a common background set. Each element from the common background set has a score that reflects its presence in several PAR-CLIP datasets. We present a tool that uses this score to identify the amount of common backgrounds present in a PAR-CLIP dataset, and we provide the user the option to use or remove it. We used the proposed strategy in 30 PAR-CLIP datasets from nine proteins. It is possible to identify the presence of common backgrounds in a dataset and identify differences in datasets for the same protein. This method is the first step in the process of completely removing such backgrounds. AVAILABILITY: The tool was implemented in python. The common background set and the supplementary data are available at https://github.com/phrh/BackCLIP. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. RESULTS: The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. CONCLUSIONS: The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between sensitivity and specificity. miREE obtains a reasonable trade-off between filtering false positives and identifying targets. miREE tool is available online at http://didattica-online.polito.it/eda/miREE/

Gene regulation is one of the most important processes in the molecular biology, in the last years the microRNA molecule, one of the non-coding RNAs involved in the process, has been the focus of attention for several studies. The computational research on this area has gained a notable importance, considering the low amount of experimental information available and the lack of understanding of the microRNA binding mechanism. This article deals with the microRNA-target prediction and presents an innovative method for it. First it generates a set of promising binding sites for a given microRNA using a Genetic Algorithm, at the same time a set of target genes is selected based on the biological process under study. Secondly the set of promising binding sites is mapped into the selected set of target genes, in order to provide real binding sites and finally the resulting targets are filtered according to a biological or structural property. The objectives are to provide a flexible method that is capable of incorporating easily new knowledge, is independent of availability of the experimental information and is able to give hints on the research towards new characteristics among the microRNA binding sites such as motifs. The results present some of this novel properties and present a comparison with the most frequently used methods in the field.