Universität zu Köln

Garmhausen, Marius, Hofmann, Falko ORCID: 0000-0002-5032-0411, Senderov, Viktor, Thomas, Maria ORCID: 0000-0001-6394-8710, Kandel, Benjamin A. and Habermann, Bianca Hermine (2015). Virtual pathway explorer (viPEr) and pathway enrichment analysis tool (PEANuT): creating and analyzing focus networks to identify cross-talk between molecules and pathways. BMC Genomics, 16. LONDON: BIOMED CENTRAL LTD. ISSN 1471-2164

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Garmhausen, Marius UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Falko UNSPECIFIED orcid.org/0000-0002-5032-0411 UNSPECIFIED Senderov, Viktor UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Maria UNSPECIFIED orcid.org/0000-0001-6394-8710 UNSPECIFIED Kandel, Benjamin A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Habermann, Bianca Hermine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-389815
DOI:	10.1186/s12864-015-2017-z
Journal or Publication Title:	BMC Genomics
Volume:	16
Date:	2015
Publisher:	BIOMED CENTRAL LTD
Place of Publication:	LONDON
ISSN:	1471-2164
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HMG-COA REDUCTASE; GENE-EXPRESSION PROFILES; APOLIPOPROTEIN-B GENE; TRANSCRIPTIONAL REGULATION; MEVALONATE PATHWAY; STATINS; PROTEIN; DATABASE; THERAPY; CANCER Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38981