Effectiveness and Usability of Bioinformatics Tools to Analyze Pathways Associated with miRNA Expression

Abstract

MiRNAs are small, nonprotein-coding RNA molecules involved in gene regulation. While bioinformatics help guide miRNA research, it is less clear how they perform when studying biological pathways. We used 13 criteria to evaluate effectiveness and usability of existing bioinformatics tools. We evaluated the performance of six bioinformatics tools with a cluster of 12 differentially expressed miRNAs in colorectal tumors and three additional sets of 12 miRNAs that are not part of a known cluster. MiRPath performed the best of all the tools in linking miRNAs, with 92% of all miRNAs linked as well as the highest based on our established criteria followed by Ingenuity (58% linked). Other tools, including Empirical Gene Ontology, miRó, miRMaid, and PhenomiR, were limited by their lack of available tutorials, lack of flexibility and interpretability, and/or difficulty using the tool. In summary, we observed a lack of standardization across bioinformatic tools and a general lack of specificity in terms of pathways identified between groups of miRNAs. Hopefully, this evaluation will help guide the development of new tools.

Lung microRNA Profiling Across the Estrous Cycle in Ozone-exposed Mice

“…The functional analysis software databases include: experimentally validated microRNA-mRNA interactions databases 23,24 , predicted microRNA-mRNA interaction database with low-confidence interactions excluded (e.g., Target Scan) 25 , experimentally validated human, rat, and mouse microRNA-mRNA interactions databases (e.g., miRecords) 26 , and literature findings (e.g., microRNA-related findings manually curated from published literature by scientific experts). Other studies comparing the effectiveness and usability of bioinformatics tools to analyze pathways associated with miRNA expression confirm the effectiveness of this software 27 . Overall, computational methods are cost-effective, less time-consuming, and can be easily validated by molecular methods.…”

Tools for Sequence-Based miRNA Target Prediction: What to Choose?

“…In recent years, thanks to the large amount of data from massive sequencing technologies, new tools have been created for miRNA:target prediction. These new tools attempt to explain statistically the observed expression patterns and include information about relationship networks in order to detect the miRNA regulatory module, thereby improving the prediction accuracy (for more information see [102]). Moreover, the use of scripts and packages provides more precise miRNA target prediction for each particular case.…”

“…Moreover, the use of scripts and packages provides more precise miRNA target prediction for each particular case. Despite all this information, it is important to bear in mind that of all the miRNA genes predicted currently, only ~25% have been validated [102], meaning there is no guarantee that all the predictions made by these tools can be validated biologically.…”

Dietary impact of a plant-derived microRNA on the gut microbiome

“…Six potential Arabidopsis mRNA targets of miR-146a were identified ( Supplemental Table 1 ), none of which appeared to be directly related to genes impacting nutrient levels. However, these predictions are often experimentally difficult to validate [ 22 ] making it necessary to analyze the macronutrient content of our diets. We cultivated isogenic Arabidopsis plants expressing either empty vector as a control (vector) or the murine miR-146a miRNA (146a) and mixed plant material with chow and water 1: 2:2 w/w/w to prepare the diets [ 23 ].…”