Fewer than one percent of proteins have experimentally validated functions. In order to predict enzyme reactions and substrates in the other 99%, we combined Evolutionary Trace Annotations (ETA) of molecular evolution with the Cytoscape graph visualisation environment. The result is the ETAscape plugin, which builds a structural genomics network based on local structural and evolutionary similarities among proteins and then propagates known annotations across the entire network by global diffusion. The plugin displays these novel functional annotations, their significance, and the molecular basis and connections that led to them. In benchmarks, these predictions are over 97% accurate at 50% coverage and at the highest level of functional resolution of Enzyme Commission, they can suggest both the chemical activity and substrate of an enzyme.

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Installation Instructions

  • You must have Cytoscape 2.8.2 installed before installing ETAscape. ETAscape is not compatible with older versions, and does not work with Cytoscape 3.0 and later versions.
  • In your Cytoscape directory (C:\Program Files\Cytoscape_v2.8.2\ by default on a Windows machine), place the etascape.jar file into the plugins directory.
  • The next time you run Cytoscape, ETAscape will guide you through the initial tutorial.
Manual for ETAscape
Video tutorial: