title: Virtual pathway explorer (viPEr) and pathway enrichment analysis tool (PEANuT): creating and analyzing focus networks to identify cross-talk between molecules and pathways.
abstract: BACKGROUND
  Interpreting large-scale studies from microarrays or next-generation sequencing for further experimental testing remains one of the major challenges in quantitative biology. Combining expression with physical or genetic interaction data has already been successfully applied to enhance knowledge from all types of high-throughput studies. Yet, toolboxes for navigating and understanding even small gene or protein networks are poorly developed.
  
  
  RESULTS
  We introduce two Cytoscape plug-ins, which support the generation and interpretation of experiment-based interaction networks. The virtual pathway explorer viPEr creates so-called focus networks by joining a list of experimentally determined genes with the interactome of a specific organism. viPEr calculates all paths between two or more user-selected nodes, or explores the neighborhood of a single selected node. Numerical values from expression studies assigned to the nodes serve to score identified paths. The pathway enrichment analysis tool PEANuT annotates networks with pathway information from various sources and calculates enriched pathways between a focus and a background network. Using time series expression data of atorvastatin treated primary hepatocytes from six patients, we demonstrate the handling and applicability of viPEr and PEANuT. Based on our investigations using viPEr and PEANuT, we suggest a role of the FoxA1/A2/A3 transcriptional network in the cellular response to atorvastatin treatment. Moreover, we find an enrichment of metabolic and cancer pathways in the Fox transcriptional network and demonstrate a patient-specific reaction to the drug.
  
  
  CONCLUSIONS
  The Cytoscape plug-in viPEr integrates -omics data with interactome data. It supports the interpretation and navigation of large-scale datasets by creating focus networks, facilitating mechanistic predictions from -omics studies. PEANuT provides an up-front method to identify underlying biological principles by calculating enriched pathways in focus networks.
authors.affiliation: CECAD Research Center, Joseph-Stelzmann-Str. 26, 50931, Cologne, Germany. marius.garmhausen@smail.uni-koeln.de.
authors.forename: Marius
authors.initials: M
authors.lastname: Garmhausen
authors.affiliation: Gregor Mendel Institute of Molecular Plant Biology, Austrian Acacdemy of Sciences, Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria. falko.hofmann@gmi.oeaw.ac.at.
authors.forename: Falko
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: Research Group Computational Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany. vsenderov@gmail.com.|Present address: Pensoft Publisher, 1700, Sofia, Bulgaria. vsenderov@gmail.com.
authors.forename: Viktor
authors.initials: V
authors.lastname: Senderov
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tübingen, Auerbachstr. 112, 70376, Stuttgart, Germany. Maria.Thomas@ikp-stuttgart.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tübingen, Auerbachstr. 112, 70376, Stuttgart, Germany. benjamin.kandel@hain-lifescience.de.|Present address: Hain Lifescience GmbH, Hardwiesenstr. 1, 72147, Nehren, Germany. benjamin.kandel@hain-lifescience.de.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Kandel
authors.affiliation: Research Group Computational Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany. habermann@biochem.mpg.de.
authors.forename: Bianca Hermine
authors.initials: BH
authors.lastname: Habermann
mesh_terms: D019295:Computational Biology; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D060066:Protein Interaction Maps / Q000235:genetics*; D012984:Software; D014584:User-Computer Interface