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