title: MiRImpact, a new bioinformatic method using complete microRNA expression profiles to assess their overall influence on the activity of intracellular molecular pathways.
abstract: MicroRNAs (miRs) are short noncoding RNA molecules that regulate expression of target mRNAs. Many published sources provide information about miRs and their targets. However, bioinformatic tools elucidating higher level impact of the established total miR profiles, are still largely missing. Recently, we developed a method termed OncoFinder enabling quantification of the activities of intracellular molecular pathways basing on gene expression data. Here we propose a new technique, MiRImpact, which enables to link miR expression data with its estimated outcome on the regulation of molecular pathways, like signaling, metabolic, cytoskeleton rearrangement, and DNA repair pathways. MiRImpact uses OncoFinder rationale for pathway activity calculations, with the major distinctions that (i) it deals with the concentrations of miRs--known regulators of gene products participating in molecular pathways, and (ii) miRs are considered as negative regulators of target molecules, if other is not specified. MiRImpact operates with 2 types of databases: for molecular targets of miRs and for gene products participating in molecular pathways. We applied MiRImpact to compare regulation of human bladder cancer-specific signaling pathways at the levels of mRNA and miR expression. We took 2 most complete alternative databases of experimentally validated miR targets--miRTarBase and DianaTarBase, and an OncoFinder database featuring 2725 gene products and 271 signaling pathways. We showed that the impact of miRs is orthogonal to pathway regulation at the mRNA level, which stresses the importance of studying posttranscriptional regulation of gene expression. We also report characteristic set of miR and mRNA regulation features linked with bladder cancer.
authors.affiliation: a Pathway Pharmaceuticals , Wan Chai , Hong Kong, Hong Kong SAR.|b Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.
authors.forename: Alina V
authors.initials: AV
authors.lastname: Artcibasova
authors.affiliation: c First Oncology Research and Advisory Center , Moscow , Russia.
authors.forename: Mikhail B
authors.initials: MB
authors.lastname: Korzinkin
authors.affiliation: a Pathway Pharmaceuticals , Wan Chai , Hong Kong, Hong Kong SAR.|c First Oncology Research and Advisory Center , Moscow , Russia.
authors.forename: Maksim I
authors.initials: MI
authors.lastname: Sorokin
authors.affiliation: d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Shegay
authors.affiliation: b Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Zhavoronkov
authors.affiliation: e Moscow State University, Faculty of Fundamental Medicine , Moscow , Russia.
authors.forename: Nurshat
authors.initials: N
authors.lastname: Gaifullin
authors.affiliation: d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia.
authors.forename: Boris Y
authors.initials: BY
authors.lastname: Alekseev
authors.affiliation: d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Vorobyev
authors.affiliation: f Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry , Moscow , Russia.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Kuzmin
authors.affiliation: d P.A. Herzen Moscow Oncological Research Institute , Moscow , Russia.
authors.forename: Аndrey D
authors.initials: АD
authors.lastname: Kaprin
authors.affiliation: g National Research Centre "Kurchatov Institute," Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies , Moscow , Russia.
authors.forename: Nikolay M
authors.initials: NM
authors.lastname: Borisov
authors.affiliation: b Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.|f Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry , Moscow , Russia.|g National Research Centre "Kurchatov Institute," Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies , Moscow , Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Buzdin
mesh_terms: D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction; D059467:Transcriptome; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs
keywords: bladder cancer; gene expression; intracellular signaling pathway activation; micro RNA; molecular markers; new bioinformatic method; total impact of miR expression