The multiMiR R package and database: integration of microRNA–target interactions along with their disease and drug associations

Abstract

microRNAs (miRNAs) regulate expression by promoting degradation or repressing translation of target transcripts. miRNA target sites have been catalogued in databases based on experimental validation and computational prediction using various algorithms. Several online resources provide collections of multiple databases but need to be imported into other software, such as R, for processing, tabulation, graphing and computation. Currently available miRNA target site packages in R are limited in the number of databases, types of databases and flexibility. We present multiMiR, a new miRNA–target interaction R package and database, which includes several novel features not available in existing R packages: (i) compilation of nearly 50 million records in human and mouse from 14 different databases, more than any other collection; (ii) expansion of databases to those based on disease annotation and drug microRNAresponse, in addition to many experimental and computational databases; and (iii) user-defined cutoffs for predicted binding strength to provide the most confident selection. Case studies are reported on various biomedical applications including mouse models of alcohol consumption, studies of chronic obstructive pulmonary disease in human subjects, and human cell line models of bladder cancer metastasis. We also demonstrate how multiMiR was used to generate testable hypotheses that were pursued experimentally.

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…In addition, specific algorithms to identify possible targets of dysregulated miRNAs in breast tumors and BCa cell lines have been reported (Cava, et al 2014;Liang, et al 2016;O'Day and Lal 2010;Ru, et al 2015;). More recently, various strategies to directly identify miRNA:RNA targets and RNA modifications by protein:RNA immunoprecipitation and high-throughput RNA seq have been used to examine protein:RNA interactions in human biology, e.g, HITS-CLIP (high-throughput RNA-seq isolated by crosslinking immunoprecipitation) (Darnell 2010); PAR-CLIP (photoactivatable ribonucleosideenhanced CLIP) (Farazi, et al 2014), iCLIP (crosslinking and immunoprecipitation) (Hong, et al 2015), eCLIP (enhanced CLIP) (Van Nostrand, et al 2016), and dCLIP (denaturing CLIP) .…”

The discordant method: a novel approach for differential correlation

“…Cancer-related miRNAs were accessed from multiMiR and miRcancer (Ru et al, 2014;Xie et al, 2013). We collected miRNAs on four cancers, including GBM as well as breast cancer, prostate cancer and melanoma as negative controls.…”

Transcriptome Analysis of Non‐Coding RNAs in Livestock Species: Elucidating the Ambiguity

“…miRWalk, a comprehensive database developed by Dweep et al [116] documents miRNA binding sites within the complete sequence of a gene and combines this information with predicted [118]. It allows user-deined cut-ofs for predicted binding strength to provide the most conident selection.…”