CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data

Abstract

Summary: The CluePedia Cytoscape plugin is a search tool for new markers potentially associated to pathways. CluePedia calculates linear and non-linear statistical dependencies from experimental data. Genes, proteins and miRNAs can be connected based on in silico and/or experimental information and integrated into a ClueGO network of terms/pathways. Interrelations within each pathway can be investigated, and new potential associations may be revealed through gene/protein/miRNA enrichments. A pathway-like visualization can be created using the Cerebral plugin layout. Combining all these features is essential for data interpretation and the generation of new hypotheses. The CluePedia Cytoscape plugin is user-friendly and has an expressive and intuitive visualization.

Availability: http://www.ici.upmc.fr/cluepedia/ and via the Cytoscape plugin manager. The user manual is available at the CluePedia website.

Fig. 1.

CluePedia analysis example using expression data from human normal colon mucosa and colorectal tumors and in silico information. (a) Functionally grouped network with pathways and genes. Terms are linked based on κ score (≥0.3). Edges show known activation (green), expression (yellow), post-translational modification (pink) and binding (blue). The edge thickness is scaled between the minimum and maximum scores shown. Terms and their associated genes share the color. ‘Regulation of IFNG signaling’ pathway is investigated in a subnetwork. (b) Genes not included in the initial selection are colored in white. Known interactions are shown. (c) Gene interrelations in normal samples are shown as Pearson correlation (blue) and MIC (orange), all values >0.7. Normalized expression data from five normal colon samples are shown as node label for IFNGR1 and IFNGR2. All spots corresponding to a gene are shown. (d) Pathway-like view of the network showing cellular locations. (e) ‘Regulation of IFNG signaling’ after enrichment steps. Five strongest correlating genes (Pearson) in normal colon and tumors, as well as the top five validated and predicted miRNAs (prediction score) are shown in blue, red, brown and beige, respectively. Negative correlations are shown as sinusoidal lines