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

Author:

Lamb Justin12345,Crawford Emily D.12345,Peck David12345,Modell Joshua W.12345,Blat Irene C.12345,Wrobel Matthew J.12345,Lerner Jim12345,Brunet Jean-Philippe12345,Subramanian Aravind12345,Ross Kenneth N.12345,Reich Michael12345,Hieronymus Haley12345,Wei Guo12345,Armstrong Scott A.12345,Haggarty Stephen J.12345,Clemons Paul A.12345,Wei Ru12345,Carr Steven A.12345,Lander Eric S.12345,Golub Todd R.12345

Affiliation:

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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