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The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
Justin Lamb,1*
Emily D. Crawford,1
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 functionalconnections among diseases, genetic perturbation, and drug action,we have created the first installment of a reference collectionof gene-expression profiles from cultured human cells treatedwith bioactive small molecules, together with pattern-matchingsoftware to mine these data. We demonstrate that this "ConnectivityMap" resource can be used to find connections among small moleculessharing a mechanism of action, chemicals and physiological processes,and diseases and drugs. These results indicate the feasibilityof the approach and suggest the value of a large-scale communityConnectivity 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.
Present address: University of California, San Francisco, CA94158, USA.
* To whom correspondence should be addressed. E-mail: golub{at}broad.harvard.edu, justin{at}broad.mit.edu
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Present address: University of California, San Francisco, CA 94158, USA. 
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*
