02435nas a2200289 4500008004100000022001400041245005500055210005400110260001600164300001200180490000700192520155100199653002601750653003001776653001801806653002901824653004201853653001101895653001401906653001401920653003101934100002901965700002201994700002002016700002002036856008902056 2016 eng d a1367-481100aIntegrated gene set analysis for microRNA studies.0 aIntegrated gene set analysis for microRNA studies c2016 Sep 15 a2809-160 v323 a

MOTIVATION: Functional interpretation of miRNA expression data is currently done in a three step procedure: select differentially expressed miRNAs, find their target genes, and carry out gene set overrepresentation analysis Nevertheless, major limitations of this approach have already been described at the gene level, while some newer arise in the miRNA scenario.Here, we propose an enhanced methodology that builds on the well-established gene set analysis paradigm. Evidence for differential expression at the miRNA level is transferred to a gene differential inhibition score which is easily interpretable in terms of gene sets or pathways. Such transferred indexes account for the additive effect of several miRNAs targeting the same gene, and also incorporate cancellation effects between cases and controls. Together, these two desirable characteristics allow for more accurate modeling of regulatory processes.

RESULTS: We analyze high-throughput sequencing data from 20 different cancer types and provide exhaustive reports of gene and Gene Ontology-term deregulation by miRNA action.

AVAILABILITY AND IMPLEMENTATION: The proposed methodology was implemented in the Bioconductor library mdgsa http://bioconductor.org/packages/mdgsa For the purpose of reproducibility all of the scripts are available at https://github.com/dmontaner-papers/gsa4mirna

CONTACT: : david.montaner@gmail.com

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

10aComputational Biology10aGene Expression Profiling10aGene ontology10aGene Regulatory Networks10aHigh-Throughput Nucleotide Sequencing10aHumans10aMicroRNAs10aNeoplasms10aReproducibility of Results1 aGarcia-Garcia, Francisco1 aPanadero, Joaquin1 aDopazo, Joaquin1 aMontaner, David uhttps://www.clinbioinfosspa.es/content/integrated-gene-set-analysis-microrna-studies