CyREST: Turbocharging Cytoscape Access for External Tools via a RESTful API. As bioinformatic workflows become increasingly complex and involve multiple specialized tools, so does the difficulty of reliably reproducing those workflows. Cytoscape is a critical workflow component for executing network visualization, analysis, and publishing tasks, but it can be operated only manually via a point-and-click user interface. Consequently, Cytoscape-oriented tasks are laborious and often error prone, especially with multistep protocols involving many networks. In this paper, we present the new cyREST Cytoscape app and accompanying harmonization libraries. Together, they improve workflow reproducibility and researcher productivity by enabling popular languages (e.g., Python and R, JavaScript, and C#) and tools (e.g., IPython/Jupyter Notebook and RStudio) to directly define and query networks, and perform network analysis, layouts and renderings. We describe cyREST’s API and overall construction, and present Python- and R-based examples that illustrate how Cytoscape can be integrated into large scale data analysis pipelines. cyREST is available in the Cytoscape app store ( where it has been downloaded over 1900 times since its release in late 2014