4.8 Article

Image-based multivariate profiling of drug responses from single cells

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NATURE METHODS
卷 4, 期 5, 页码 445-453

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NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH1032

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  1. NIGMS NIH HHS [R01 GM081549] Funding Source: Medline

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Quantitative analytical approaches for discovering new compound mechanisms are required for summarizing high-throughput, image-based drug screening data. Here we present a multivariate method for classifying untreated and treated human cancer cells based on B300 single-cell phenotypic measurements. This classification provides a score, measuring the magnitude of the drug effect, and a vector, indicating the simultaneous phenotypic changes induced by the drug. These two quantities were used to characterize compound activities and identify dose-dependent multiphasic responses. A systematic survey of profiles extracted from a 100-compound compendium of image data revealed that only 10-15% of the original features were required to detect a compound effect. We report the most informative image features for each compound and fluorescence marker set using a method that will be useful for determining minimal collections of readouts for drug screens. Our approach provides human-interpretable profiles and automatic determination of on- and off-target effects.

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