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Open Access Highly Accessed Research article

eXamine: Exploring annotated modules in networks

Kasper Dinkla1, Mohammed El-Kebir23, Cristina-Iulia Bucur23, Marco Siderius3, Martine J Smit3, Michel A Westenberg1* and Gunnar W Klau23

Author Affiliations

1 Eindhoven University of Technology, Den Dolech 2, 5600 MB, Eindhoven, The Netherlands

2 Life Sciences, Centrum Wiskunde & Informatica (CWI), Science Park 123, 1098 XG, Amsterdam, The Netherlands

3 VU University Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands

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BMC Bioinformatics 2014, 15:201  doi:10.1186/1471-2105-15-201

Published: 7 July 2014

Abstract

Background

Biological networks have a growing importance for the interpretation of high-throughput “omics” data. Integrative network analysis makes use of statistical and combinatorial methods to extract smaller subnetwork modules, and performs enrichment analysis to annotate the modules with ontology terms or other available knowledge. This process results in an annotated module, which retains the original network structure and includes enrichment information as a set system. A major bottleneck is a lack of tools that allow exploring both network structure of extracted modules and its annotations.

Results

This paper presents a visual analysis approach that targets small modules with many set-based annotations, and which displays the annotations as contours on top of a node-link diagram. We introduce an extension of self-organizing maps to lay out nodes, links, and contours in a unified way. An implementation of this approach is freely available as the Cytoscape app eXamine

Conclusions

eXamine accurately conveys small and annotated modules consisting of several dozens of proteins and annotations. We demonstrate that eXamine facilitates the interpretation of integrative network analysis results in a guided case study. This study has resulted in a novel biological insight regarding the virally-encoded G-protein coupled receptor US28.

Keywords:
Network analysis; Module; Set-based annotation; Visualization; Cytoscape