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

Science 313: 1929-1935 (2006). Published: 2006.09.28

Justin Lamb, Emily D. Crawford, David Peck, Joshua W. Modell, Irene C. Blat, Matthew J. Wrobel, Jim Lerner, Jean-Philippe Brunet, Aravind Subramanian, Kenneth N. Ross, Michael Reich, Haley Hieronymus, Guo Wei, Scott A. Armstrong, Stephen J. Haggarty, Paul A. Clemons, Ru Wei, Steven A. Carr, Eric S. Lander and Todd R. Golub

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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.