Deep Representation Learning Determines Drug Mechanism of Action from Cell Painting Images

Abstract

Fluorescent-based microscopy screens carry a broad range of phenotypic information about how compounds affect cellular biology. From changes in cellular morphology observed in these screens, one key area of medicinal interest is determining a compounds mechanism of action. However, much of this phenotypic information is subtle and difficult to quantify. Hence, creating quantitative embeddings that can measure cellular response to compound perturbation has been a key area of research. Here we present a deep learning enabled encoder called MOAProfiler that captures phenotypic features for determining mechanism of action from Cell Painting images. We compared our method with both a traditional computer vision means of feature encoding via CellProfiler and a deep learning encoder called DeepProfiler. The results, on two independent and biologically different datasets, indicated that MOAProfiler encoded MOA-specific features that allowed for more accurate clustering and classification of compounds over hundreds of different MOAs.