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Science 306 (5699): 1194-1198

Copyright © 2004 by the American Association for the Advancement of Science

Multidimensional Drug Profiling By Automated Microscopy

Zachary E. Perlman,1,2* Michael D. Slack,3*{dagger} Yan Feng,1*{ddagger} Timothy J. Mitchison,1,2 Lani F. Wu,3§ Steven J. Altschuler3§

Abstract: We present a method for high-throughput cytological profiling by microscopy. Our system provides quantitative multidimensional measures of individual cell states over wide ranges of perturbations. We profile dose-dependent phenotypic effects of drugs in human cell culture with a titration-invariant similarity score (TISS). This method successfully categorized blinded drugs and suggested targets for drugs of uncertain mechanism. Multivariate single-cell analysis is a starting point for identifying relationships among drug effects at a systems level and a step toward phenotypic profiling at the single-cell level. Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs.

1 Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
3 Bauer Center for Genomics Research, Harvard University, Cambridge, MA 02138, USA.

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* These authors contributed equally to this work.

{dagger} Present address: Alphatech, Inc., San Diego, CA 92123, USA.

{ddagger} Present address: Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.

§ To whom correspondence should be addressed. E-mail: saltschuler{at} (S.J.A.); lwu{at} (L.F.W.)

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