Abstract
AbstractFluorescent-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 compound’s 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.
Publisher
Cold Spring Harbor Laboratory
Reference42 articles.
1. Modern Phenotypic Drug Discovery Is a Viable, Neoclassic Pharma Strategy
2. Li, Z. , Cvijic, M. E. & Zhang, L. Cellular imaging in drug discovery: Imaging and informatics for complex cell biology. in Comprehensive Medicinal Chemistry III (eds. Chackalamannil, S. , Rotella, D. & Ward, S. E .) 362–387 (Elsevier, 2017).
3. Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes
4. Weakly supervised learning of single-cell feature embeddings;Proc. IEEE Comput. Soc. Conf. Comput. Vis. Pattern Recognit,2018
5. High content phenotypic screening identifies serotonin receptor modulators with selective activity upon breast cancer cell cycle and cytokine signaling pathways;Bioorg. Med. Chem,2020
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