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The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
Justin Lamb,1*Emily D. Crawford,1David Peck,1Joshua W. Modell,1Irene C. Blat,1Matthew J. Wrobel,1Jim Lerner,1Jean-Philippe Brunet,1Aravind Subramanian,1Kenneth N. Ross,1Michael Reich,1Haley Hieronymus,1,2Guo Wei,1,2Scott A. Armstrong,2,3Stephen J. Haggarty,1,4Paul A. Clemons,1Ru Wei,1Steven A. Carr,1Eric S. Lander,1,5,6Todd R. Golub1,2,3,5,7*
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. 
