title: CyTRANSFINDER: a Cytoscape 3.3 plugin for three-component (TF, gene, miRNA) signal transduction pathway construction.
abstract: BACKGROUND
  Biological research increasingly relies on network models to study complex phenomena. Signal Transduction Pathways are molecular circuits that model how cells receive, process, and respond to information from the environment providing snapshots of the overall cell dynamics. Most of the attempts to reconstruct signal transduction pathways are limited to single regulator networks including only genes/proteins. However, networks involving a single type of regulator and neglecting transcriptional and post-transcriptional regulations mediated by transcription factors and microRNAs, respectively, may not fully reveal the complex regulatory mechanisms of a cell. We observed a lack of computational instruments supporting explorative analysis on this type of three-component signal transduction pathways.
  
  
  RESULTS
  We have developed CyTRANSFINDER, a new Cytoscape plugin able to infer three-component signal transduction pathways based on user defined regulatory patterns and including miRNAs, TFs and genes. Since CyTRANSFINDER has been designed to support exploratory analysis, it does not rely on expression data. To show the potential of the plugin we have applied it in a study of two miRNAs that are particularly relevant in human melanoma progression, miR-146a and miR-214.
  
  
  CONCLUSIONS
  CyTRANSFINDER supports the reconstruction of small signal transduction pathways among groups of genes. Results obtained from its use in a real case study have been analyzed and validated through both literature data and preliminary wet-lab experiments, showing the potential of this tool when performing exploratory analysis.
authors.affiliation: Department of Control and Computer Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, 10129, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Politano
authors.affiliation: Molecular Biotechnology Center (MBC), Via Nizza, 52, Torino, 10126, Italy.|Dept. Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza, 52, Torino, 10126, Italy.|Center for Complex Systems in Molecular Biology and Medicine, Via Accademia Albertina, 13, Torino, 10123, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.affiliation: Molecular Biotechnology Center (MBC), Via Nizza, 52, Torino, 10126, Italy.|Dept. Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza, 52, Torino, 10126, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Raimo
authors.affiliation: Department of Control and Computer Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, 10129, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Benso
authors.affiliation: Department of Control and Computer Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, 10129, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Savino
authors.affiliation: Molecular Biotechnology Center (MBC), Via Nizza, 52, Torino, 10126, Italy.|Dept. Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza, 52, Torino, 10126, Italy.|Center for Complex Systems in Molecular Biology and Medicine, Via Accademia Albertina, 13, Torino, 10123, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.affiliation: Department of Control and Computer Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, 10129, Italy. stefano.dicarlo@polito.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Carlo
mesh_terms: D018450:Disease Progression; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008545:Melanoma / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C542542:MIRN146 microRNA, human; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors
keywords: Cytoscape; Data fusion; Network analysis; Network modules; Pathway analysis; Signal transduction pathways; microRNA