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. 2013 Aug 1;29(15):1872-8.
doi: 10.1093/bioinformatics/btt319. Epub 2013 Jun 7.

Network2Canvas: Network Visualization on a Canvas With Enrichment Analysis

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Free PMC article

Network2Canvas: Network Visualization on a Canvas With Enrichment Analysis

Christopher M Tan et al. Bioinformatics. .
Free PMC article

Abstract

Motivation: Networks are vital to computational systems biology research, but visualizing them is a challenge. For networks larger than ∼100 nodes and ∼200 links, ball-and-stick diagrams fail to convey much information. To address this, we developed Network2Canvas (N2C), a web application that provides an alternative way to view networks. N2C visualizes networks by placing nodes on a square toroidal canvas. The network nodes are clustered on the canvas using simulated annealing to maximize local connections where a node's brightness is made proportional to its local fitness. The interactive canvas is implemented in HyperText Markup Language (HTML)5 with the JavaScript library Data-Driven Documents (D3). We applied N2C to visualize 30 canvases made from human and mouse gene-set libraries and 6 canvases made from the Food and Drug Administration (FDA)-approved drug-set libraries. Given lists of genes or drugs, enriched terms are highlighted on the canvases, and their degree of clustering is computed. Because N2C produces visual patterns of enriched terms on canvases, a trained eye can detect signatures instantly. In summary, N2C provides a new flexible method to visualize large networks and can be used to perform and visualize gene-set and drug-set enrichment analyses.

Availability: N2C is freely available at http://www.maayanlab.net/N2C and is open source.

Contact: avi.maayan@mssm.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Figures

Fig. 1.
Fig. 1.
The N2C workflow. Taking a mean adjacency matrix derived from a network as input, the Annealer places terms onto a square toroidal grid and anneals them for a user-defined duration, outputting a JSON file. The Visualizer reads this file and colors the canvas. Enrichment analysis highlights terms on the canvas, calculates the degree of clustering and outputs a table of the top 20 enriched terms and their P-values
Fig. 2.
Fig. 2.
Canvases for the 30 gene-set libraries. Each canvas represents a gene-set library. In each canvas, each node (square) represents a gene list associated with a gene-set library term. The terms are arranged on the canvas based on their gene-set content similarity. The brightness of each node is determined by its similarity to its eight neighbors. Canvases are color coded based on their category: pathways, cyan; transcription, purple; ontologies, green; disease/drugs, yellow; cell types, red and miscellaneous, blue
Fig. 3.
Fig. 3.
Twelve canvases for the six drug-set libraries. Each canvas represents a drug-set library where each node (square) is an FDA-approved drug (blue canvases) or an FDA-approved drug property, e.g. a side effect or a structural element. Nodes are arranged based on their drug property similarity (for the drug canvases) or based on drug content similarity (for the drug property canvases). Nodes are colored based on their similarity to their neighbors: the brighter the spot, the higher the similarity. The six drug property set library canvases are the inverse of the six drug-set library canvases, all made from the original six drug-set library
Fig. 4.
Fig. 4.
Screenshot from the N2C web application. The interactive user interface of N2C provides users with the ability to select the desired canvas (KEGG is selected a default), change the canvas colors, highlight specific nodes on the canvas, perform enrichment analyses and explore the content of each node. The enrichment results are displayed in a table and can be exported
Fig. 5.
Fig. 5.
Meta-signatures using various gene-set libraries applied to gene lists extracted from gene expression microarrays after knockdown of various transcription factors in mESCs. Only enriched terms are highlighted on the canvas. Brighter nodes represent lower P-value enriched terms
Fig. 6.
Fig. 6.
Canvas for the 128 structural elements, also called Molecular ACCess System (MACCS) keys, using the P-value view in N2C show enrichment for MACCS keys for drug lists associated with the side effects of cardiac arrest, coma and pancreatitis

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