Intuitive Unsupervised On/Off Target Assessment using Magellan Plots

SBI2, Boston, MA, USA
September 19, 2022

Drug molecules often interact with multiple targets, and understanding this polypharmacology is of particular interest in terms of assessing potential side effects, off target effects or toxicity - a major challenge in drug development. 
To support this complex assessment, we developed a new plot type and illustrate its use using high-content image data. This new plot, called the Magellan plot, provides an intuitive visual aid for understanding of on- and off-target effects and their dose-dependent dynamics. In applying unsupervised clustering on these dosing dynamics, we successfully uncovered clusters of on-target versus off-target effects of compounds at specific doses. 
We illustrate the basic workflow and show examples of Magellan plots from an industry-relevant, high-content receptor internalization screen.