Virtual pathway explorer (viPEr) and pathway enrichment analysis tool (PEANuT): creating and analyzing focus networks to identify cross-talk between molecules and pathways

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2017-z) contains supplementary material, which is available to authorized users

Are MPNs vascular diseases?

A high risk of arterial and venous thrombosis is the hallmark of chronic myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Clinical aspects, pathogenesis and management of thrombosis in MPN resemble those of other paradigmatic vascular diseases. The occurrence of venous thrombosis in atypical sites, such as the splanchnic district, and the involvement of plasmatic prothrombotic factors, including an acquired resistance to activated protein C, both link MPN to inherited thrombophilia. Anticoagulants are the drugs of choice for these complications. The pathogenic role of leukocytes and inflammation, and the high mortality rate from arterial occlusions are common features of MPN and atherosclerosis. The efficacy and safety of aspirin in reducing deaths and major thrombosis in PV have been demonstrated in a randomized clinical trial. Finally, the Virchow's triad of impaired blood cells, endothelium and blood flow is shared both by MPN and thrombosis in solid cancer. Phlebotomy and myelosuppressive agents are the current therapeutic options for correcting these abnormalities and reducing thrombosis in this special vascular disease represented by MPN