eXamine: Exploring annotated modules in networks

TL;DR

eXamine is a visualization tool that helps explore and interpret small, annotated modules in biological networks by combining network structure and annotation contours, facilitating biological insights.

Contribution

This paper introduces eXamine, a novel Cytoscape app that visualizes annotated network modules with contours, enhancing interpretability of integrative network analysis results.

Findings

eXamine accurately visualizes small, annotated modules.

It enables biological interpretation of network modules.

The tool facilitated a new biological insight in a case study.

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: Thispaperpresentsavisualanalysisapproachthattargetssmallmoduleswithmanyset-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.