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Science 313 (5795): 1929-1935

Copyright © 2006 by the American Association for the Advancement of Science

The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease

Justin Lamb,1* Emily D. Crawford,1{dagger} David Peck,1 Joshua W. Modell,1 Irene C. Blat,1 Matthew J. Wrobel,1 Jim Lerner,1 Jean-Philippe Brunet,1 Aravind Subramanian,1 Kenneth N. Ross,1 Michael Reich,1 Haley Hieronymus,1,2 Guo Wei,1,2 Scott A. Armstrong,2,3 Stephen J. Haggarty,1,4 Paul A. Clemons,1 Ru Wei,1 Steven A. Carr,1 Eric S. Lander,1,5,6 Todd R. Golub1,2,3,5,7*

Abstract: To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map" resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project.

1 Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
2 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
3 Department of Medicine, Children's Hospital Boston, Boston, MA 02115, USA.
4 Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02144, USA.
5 Harvard Medical School, Boston, MA 02115, USA.
6 Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
7 Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

{dagger} Present address: University of California, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: golub{at}broad.harvard.edu, justin{at}broad.mit.edu

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Identification of novel hair-growth inducers by means of connectivity mapping.
Y. Ishimatsu-Tsuji, T. Soma, and J. Kishimoto (2010)
FASEB J 24, 1489-1496
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The Connectivity Map Links Iron Regulatory Protein-1-Mediated Inhibition of Hypoxia-Inducible Factor-2a Translation to the Anti-inflammatory 15-deoxy-{Delta}12,14-Prostaglandin J2.
M. Zimmer, J. Lamb, B. L. Ebert, M. Lynch, C. Neil, E. Schmidt, T. R. Golub, and O. Iliopoulos (2010)
Cancer Res. 70, 3071-3079
   Abstract »    Full Text »    PDF »
Bayesian approach to transforming public gene expression repositories into disease diagnosis databases.
H. Huang, C.-C. Liu, and X. J. Zhou (2010)
PNAS 107, 6823-6828
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