CyTargetLinker: A Cytoscape App to Integrate Regulatory Interactions in Network Analysis

Abstract

IntroductionThe high complexity and dynamic nature of the regulation of gene expression, protein synthesis, and protein activity pose a challenge to fully understand the cellular machinery. By deciphering the role of important players, including transcription factors, microRNAs, or small molecules, a better understanding of key regulatory processes can be obtained. Various databases contain information on the interactions of regulators with their targets for different organisms, data recently being extended with the results of the ENCODE (Encyclopedia of DNA Elements) project. A systems biology approach integrating our understanding on different regulators is essential in interpreting the regulation of molecular biological processes.ImplementationWe developed CyTargetLinker (http://projects.bigcat.unimaas.nl/cytargetlinker), a Cytoscape app, for integrating regulatory interactions in network analysis. Recently we released CyTargetLinker as one of the first apps for Cytoscape 3. It provides a user-friendly and flexible interface to extend biological networks with regulatory interactions, such as microRNA-target, transcription factor-target and/or drug-target. Importantly, CyTargetLinker employs identifier mapping to combine various interaction data resources that use different types of identifiers.ResultsThree case studies demonstrate the strength and broad applicability of CyTargetLinker, (i) extending a mouse molecular interaction network, containing genes linked to diabetes mellitus, with validated and predicted microRNAs, (ii) enriching a molecular interaction network, containing DNA repair genes, with ENCODE transcription factor and (iii) building a regulatory meta-network in which a biological process is extended with information on transcription factor, microRNA and drug regulation.ConclusionsCyTargetLinker provides a simple and extensible framework for biologists and bioinformaticians to integrate different regulatory interactions into their network analysis approaches. Visualization options enable biological interpretation of complex regulatory networks in a graphical way. Importantly the incorporation of our tool into the Cytoscape framework allows the application of CyTargetLinker in combination with a wide variety of other apps for state-of-the-art network analysis.

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

“…Molecular targets for each miRNA were retrieved and the validated miRNA-target interaction network was obtained from the CyTargetLinker plugin in the Cytoscape environment (25). The network containing interactions between differentially expressed miRNA and putative targets was constructed and visualized using Cytoscape (http://cytoscape.org) (26).…”

MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia

“…Molecular targets for each miRNAs were retrieved and the validated miRNA-target interaction network was obtained from the CyTargetLinker plugin in the Cytoscape environment (Kutmon et al, 2013). CyTargetLinker (http://projects.bigcat.unimaas.nl/ cytargetlinker), a Cytoscape apparatus, provides an extensible framework to integrate different regulatory interactions from databases including MicroCosm, TargetScan, miRTarBase, ENCODE, TFe and DrugBank.…”

Association of miR-193b Down-regulation and miR-196a up-Regulation with Clinicopathological Features and Prognosis in Gastric Cancer

“…To investigate the biological properties of differentially expressed miRNAs, the validated target genes of miR193b and miR-196a were retrieved via CyTargetLinker (Kutmon et al, 2013) in Cytoscape v3.1.1 software (San Diego, CA, USA) (Shannon et al, 2003). Pathway enrichment analysis was then performed via ClueGO (ontologies and pathways provided by GO Biological process, GO Molecular function, GO Immune system, Kyoto Encyclopedia of Genes and Genomes (KEGG), and REACTOME) (Bindea et al, 2009).…”