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

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; Todd R. Golub

doi:10.1126/science.1132939

Research Article

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

Justin Lamb1,*,
Emily D. Crawford1,†,
David Peck1,
Joshua W. Modell1,
Irene C. Blat1,
Matthew J. Wrobel1,
Jim Lerner1,
Jean-Philippe Brunet1,
Aravind Subramanian1,
Kenneth N. Ross1,
Michael Reich1,
Haley Hieronymus1,2,
Guo Wei1,2,
Scott A. Armstrong2,3,
Stephen J. Haggarty1,4,
Paul A. Clemons1,
Ru Wei1,
Steven A. Carr1,
Eric S. Lander1,5,6,
Todd R. Golub1,2,3,5,7,*

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.

↵* To whom correspondence should be addressed. E-mail: golub{at}broad.harvard.edu, justin{at}broad.mit.edu

↵† Present address: University of California, San Francisco, CA 94158, USA.

See allHide authors and affiliations

Science 29 Sep 2006:
Vol. 313, Issue 5795, pp. 1929-1935
DOI: 10.1126/science.1132939

Justin Lamb

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
For correspondence: golub@broad.harvard.edu justin@broad.mit.edu

Emily D. Crawford

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

David Peck

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Joshua W. Modell

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Irene C. Blat

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Matthew J. Wrobel

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jim Lerner

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jean-Philippe Brunet

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Aravind Subramanian

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Kenneth N. Ross

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Michael Reich

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Haley Hieronymus

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Guo Wei

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Scott A. Armstrong

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Department of Medicine, Children's Hospital Boston, Boston, MA 02115, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Stephen J. Haggarty

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02144, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Paul A. Clemons

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Ru Wei

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Steven A. Carr

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Eric S. Lander

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. Harvard Medical School, Boston, MA 02115, USA. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Todd R. Golub

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Department of Medicine, Children's Hospital Boston, Boston, MA 02115, USA. Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
For correspondence: golub@broad.harvard.edu justin@broad.mit.edu

Article
Figures & Data
Info & Metrics
eLetters
PDF

You are currently viewing the abstract.

View Full Text

Log in to view the full text

via AAAS login

AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Become an AAAS Member
Activate your Account
Purchase Access to Other Journals in the Science Family
Account Help

As a service to the community, this article is available for free. Existing users log in.

Become a AAAS member
Account help

Log in through your institution

More options

Purchase digital access to this article

Download and print this article for your personal scholarly, research, and educational use.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

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.

View Full Text

Comparison of mRNAs evoked by small molecules in human cells to mRNA expressed in diseases and in response to drugs suggests new therapeutic approaches.

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

Abstract

Science

Article Tools