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Nucleic Acids Res. 2014 Jun;42(11):e96. doi: 10.1093/nar/gku354. Epub 2014 May 6.

Wiring miRNAs to pathways: a topological approach to integrate miRNA and mRNA expression profiles.

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Department of Biology, University of Padova, via U. Bassi 58/B, 35121 Padova, Italy.
Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20145 Milan, Italy.
Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia Valenta, via Malta 3, 13900 Biella, Italy.
Department of Biology, University of Padova, via U. Bassi 58/B, 35121 Padova, Italy


The production rate of gene expression data is nothing less than astounding. However, with the benefit of hindsight we can assert that, since we completely ignored the non-coding part of the transcriptome, we spent the last decade to study cell mechanisms having few data in our hands. In this scenario, microRNAs, which are key post-trascriptional regulators, deserve special attention. Given the state of knowledge about their biogenesis, mechanisms of action and the numerous experimentally validated target genes, miRNAs are also gradually appearing in the formal pathway representations such as KEGG and Reactome maps. However, the number of miRNAs annotated in pathway maps are very few and pathway analyses exploiting this new regulatory layer are still lacking. To fill these gaps, we present 'micrographite' a new pipeline to perform topological pathway analysis integrating gene and miRNA expression profiles. Here, micrographite is used to study and dissect the epithelial ovarian cancer gene and miRNA transcriptome defining and validating a new regulatory circuit related to ovarian cancer histotype specificity.

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