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Nat Methods. 2007 May;4(5):445-53. Epub 2007 Apr 1.

Image-based multivariate profiling of drug responses from single cells.

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Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., ND 9.214, Dallas, Texas 75390, USA.


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 approximately 300 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.

[Indexed for MEDLINE]

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