ETAscape: analyzing protein networks to predict enzymatic function and substrates in Cytoscape

Abstract

Most proteins lack experimentally validated functions. To address this problem, we implemented the Evolutionary Trace Annotation (ETA) method in the Cytoscape network visualization environment. The result is the ETAscape plugin, which builds a structural genomics network based on local structural and evolutionary similarities among proteins and then globally diffuses known annotations across the resulting network. The plugin displays these novel functional annotations, their confidence, the molecular basis for individual matches and the set of matches that lead to a prediction.

Availability: The ETA Network Plugin is available publicly for download at http://mammoth.bcm.tmc.edu/networks/.

Fig. 1

Screen capture of the plugin. Nodes are proteins, with colors encoding the first two EC numbers. Edges are ETA template matches and indicate local structural and evolutionary similarity. Two unknown protein structures (yellow nodes in center) are highlighted and discussed in the Overview of ETAscape section below. A Jmol window (top right) shows the protein structure for 2f2gB and its mutual template match to 1rtwD (2f2gB's template is shown in blue and 1rtwD's is shown in red, purple indicates shared residues)