Prediction methods for microRNA targets in bilaterian animals: Toward a better understanding by biologists.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Because of their wide network of interactions, miRNAs have become the focus of many studies over the past decade, particularly in animal species. To streamline the number of potential wet lab experiments, the use of miRNA target prediction tools is currently the first step undertaken. However, the predictions made may vary considerably depending on the tool used, which is mostly due to the complex and still not fully understood mechanism of action of miRNAs. The discrepancies complicate the choice of the tool for miRNA target prediction. To provide a comprehensive view of this issue, we highlight in this review the main characteristics of miRNA-target interactions in bilaterian animals, describe the prediction models currently used, and provide some insights for the evaluation of predictor performance.

Improving Bioinformatics Prediction of microRNA Targets by Ranks Aggregation.

microRNAs are noncoding RNAs which downregulate a large number of target mRNAs and modulate cell activity. Despite continued progress, bioinformatics prediction of microRNA targets remains a challenge since available software still suffer from a lack of accuracy and sensitivity. Moreover, these tools show fairly inconsistent results from one another. Thus, in an attempt to circumvent these difficulties, we aggregated all human results of four important prediction algorithms (miRanda, PITA, SVmicrO, and TargetScan) showing additional characteristics in order to rerank them into a single list. Instead of deciding which prediction tool to use, our method clearly helps biologists getting the best microRNA target predictions from all aggregated databases. The resulting database is freely available through a webtool called miRabel which can take either a list of miRNAs, genes, or signaling pathways as search inputs. Receiver operating characteristic curves and precision-recall curves analysis carried out using experimentally validated data and very large data sets show that miRabel significantly improves the prediction of miRNA targets compared to the four algorithms used separately. Moreover, using the same analytical methods, miRabel shows significantly better predictions than other popular algorithms such as MBSTAR, miRWalk, ExprTarget and miRMap. Interestingly, an F-score analysis revealed that miRabel also significantly improves the relevance of the top results. The aggregation of results from different databases is therefore a powerful and generalizable approach to many other species to improve miRNA target predictions. Thus, miRabel is an efficient tool to guide biologists in their search for miRNA targets and integrate them into a biological context.

Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients.

A stage I non-small cell lung cancer (NSCLC) serum profiling platform is presented which is highly efficient and accurate. Test sensitivity (0.95) for stage I NSCLC is the highest reported so far. Test metrics are reported for discriminating stage I adenocarcinoma vs squamous cell carcinoma subtypes. Blinded analysis identified 23 out of 24 stage I NSCLC and control serum samples. Group-discriminating mass peaks were targeted for tandem mass spectrometry peptide/protein identification, and yielded a lung cancer phenotype. Bioinformatic analysis revealed a novel lymphocyte adhesion pathway involved with early-stage lung cancer.

Distinguishing early-stage pancreatic cancer patients from disease-free individuals using serum profiling.

This study evaluated the usefulness of electrospray mass spectrometry to distinguish sera of early-stage pancreatic cancer patients from disease-free individuals. Sera peak data were generated from 33 pancreatic cancer patients and 30 disease-free individuals. A "leave one out" cross-validation procedure discriminated stage I/II pancreatic cancer versus disease-free sera with a p value <.001 and a receiver-operator characteristic curve area value of 0.85. Predictive values for cancer stage I/II test efficiency, specificity, and sensitivity were 78%, 77%, and 79%, respectively. These studies indicate that electrospray mass spectrometry is useful for distinguishing sera of early-stage pancreatic cancer patients from disease-free individuals.