Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 29 September 2006:
Vol. 313. no. 5795, pp. 1929 - 1935
DOI: 10.1126/science.1132939
Prev | Table of Contents | Next

Research Articles

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

Justin Lamb,1* Emily D. Crawford,1{dagger} David Peck,1 Joshua W. Modell,1 Irene C. Blat,1 Matthew J. Wrobel,1 Jim Lerner,1 Jean-Philippe Brunet,1 Aravind Subramanian,1 Kenneth N. Ross,1 Michael Reich,1 Haley Hieronymus,1,2 Guo Wei,1,2 Scott A. Armstrong,2,3 Stephen J. Haggarty,1,4 Paul A. Clemons,1 Ru Wei,1 Steven A. Carr,1 Eric S. Lander,1,5,6 Todd R. Golub1,2,3,5,7*

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.

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.

{dagger} Present address: University of California, San Francisco, CA 94158, USA.

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Novel pathway compendium analysis elucidates mechanism of pro-angiogenic synthetic small molecule.
K. A. Wieghaus, E. P. Gianchandani, M. A. Paige, M. L. Brown, E. A. Botchwey, and J. A. Papin (2008)
Bioinformatics 24, 2384-2390
   Abstract »    Full Text »    PDF »
Gene expression module-based chemical function similarity search.
Y. Li, P. Hao, S. Zheng, K. Tu, H. Fan, R. Zhu, G. Ding, C. Dong, C. Wang, X. Li, et al. (2008)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
A Gene Signature-Based Approach Identifies mTOR as a Regulator of p73.
J. M. Rosenbluth, D. J. Mays, M. F. Pino, L. J. Tang, and J. A. Pietenpol (2008)
Mol. Cell. Biol. 28, 5951-5964
   Abstract »    Full Text »    PDF »
A genomic approach to identify molecular pathways associated with chemotherapy resistance.
R. F. Riedel, A. Porrello, E. Pontzer, E. J. Chenette, D. S. Hsu, B. Balakumaran, A. Potti, J. Nevins, and P. G. Febbo (2008)
Mol. Cancer Ther. 7, 3141-3149
   Abstract »    Full Text »    PDF »
Curcumin Inhibits Lung Cancer Cell Invasion and Metastasis through the Tumor Suppressor HLJ1.
H.-W. Chen, J.-Y. Lee, J.-Y. Huang, C.-C. Wang, W.-J. Chen, S.-F. Su, C.-W. Huang, C.-C. Ho, J. J.W. Chen, M.-F. Tsai, et al. (2008)
Cancer Res. 68, 7428-7438
   Abstract »    Full Text »    PDF »
Transforming Growth Factor {beta} Engages TACE and ErbB3 To Activate Phosphatidylinositol-3 Kinase/Akt in ErbB2-Overexpressing Breast Cancer and Desensitizes Cells to Trastuzumab.
S. E. Wang, B. Xiang, M. Guix, M. G. Olivares, J. Parker, C. H. Chung, A. Pandiella, and C. L. Arteaga (2008)
Mol. Cell. Biol. 28, 5605-5620
   Abstract »    Full Text »    PDF »
Insulin-Like Growth Factor-I Activates Gene Transcription Programs Strongly Associated With Poor Breast Cancer Prognosis.
C. J. Creighton, A. Casa, Z. Lazard, S. Huang, A. Tsimelzon, S. G. Hilsenbeck, C. K. Osborne, and A. V. Lee (2008)
J. Clin. Oncol. 26, 4078-4085
   Abstract »    Full Text »    PDF »
From the Cover: The implications of human metabolic network topology for disease comorbidity.
D.-S. Lee, J. Park, K. A. Kay, N. A. Christakis, Z. N. Oltvai, and A.-L. Barabasi (2008)
PNAS 105, 9880-9885
   Abstract »    Full Text »    PDF »
Expression-based screening identifies the combination of histone deacetylase inhibitors and retinoids for neuroblastoma differentiation.
C. K. Hahn, K. N. Ross, I. M. Warrington, R. Mazitschek, C. M. Kanegai, R. D. Wright, A. L. Kung, T. R. Golub, and K. Stegmaier (2008)
PNAS 105, 9751-9756
   Abstract »    Full Text »    PDF »
Two strategies for gene regulation by promoter nucleosomes.
I. Tirosh and N. Barkai (2008)
Genome Res. 18, 1084-1091
   Abstract »    Full Text »    PDF »
Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.
D. C. Hassane, M. L. Guzman, C. Corbett, X. Li, R. Abboud, F. Young, J. L. Liesveld, M. Carroll, and C. T. Jordan (2008)
Blood 111, 5654-5662
   Abstract »    Full Text »    PDF »
Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate Cancer.
S. R. Setlur, K. D. Mertz, Y. Hoshida, F. Demichelis, M. Lupien, S. Perner, A. Sboner, Y. Pawitan, O. Andren, L. A. Johnson, et al. (2008)
J Natl Cancer Inst 100, 815-825
   Abstract »    Full Text »    PDF »
SNP panel identification assay (SPIA): a genetic-based assay for the identification of cell lines.
F. Demichelis, H. Greulich, J. A. Macoska, R. Beroukhim, W. R. Sellers, L. Garraway, and M. A. Rubin (2008)
Nucleic Acids Res. 36, 2446-2456
   Abstract »    Full Text »    PDF »
Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation.
Z. Arany, B. K. Wagner, Y. Ma, J. Chinsomboon, D. Laznik, and B. M. Spiegelman (2008)
PNAS 105, 4721-4726
   Abstract »    Full Text »    PDF »
Modeling Genomic Diversity and Tumor Dependency in Malignant Melanoma.
W. M. Lin, A. C. Baker, R. Beroukhim, W. Winckler, W. Feng, J. M. Marmion, E. Laine, H. Greulich, H. Tseng, C. Gates, et al. (2008)
Cancer Res. 68, 664-673
   Abstract »    Full Text »    PDF »
Revealing Targeted Therapy for Human Cancer by Gene Module Maps.
D. J. Wong, D. S.A. Nuyten, A. Regev, M. Lin, A. S. Adler, E. Segal, M. J. van de Vijver, and H. Y. Chang (2008)
Cancer Res. 68, 369-378
   Abstract »    Full Text »    PDF »
DBTSS: database of transcription start sites, progress report 2008.
H. Wakaguri, R. Yamashita, Y. Suzuki, S. Sugano, and K. Nakai (2008)
Nucleic Acids Res. 36, D97-D101
   Abstract »    Full Text »    PDF »
High-throughput screening for fatty acid uptake inhibitors in humanized yeast identifies atypical antipsychotic drugs that cause dyslipidemias.
H. Li, P. N. Black, A. Chokshi, A. Sandoval-Alvarez, R. Vatsyayan, W. Sealls, and C. C. DiRusso (2008)
J. Lipid Res. 49, 230-244
   Abstract »    Full Text »    PDF »
Current progress in network research: toward reference networks for key model organisms.
B. S. Srinivasan, N. H. Shah, J. A. Flannick, E. Abeliuk, A. F. Novak, and S. Batzoglou (2007)
Brief Bioinform 8, 318-332
   Abstract »    Full Text »    PDF »
Genetic Toxicity Assessment: Employing the Best Science for Human Safety Evaluation Part VII: Why Not Start with a Single Test: A Transformational Alternative to Genotoxicity Hazard and Risk Assessment.
W. W. Ku, J. Aubrecht, R. J. Mauthe, R. H. Schiestl, and A. J. Fornace Jr (2007)
Toxicol. Sci. 99, 20-25
   Abstract »    Full Text »    PDF »
Detecting genetic variation in microarray expression data.
J. A. Greenhall, M. A. Zapala, M. Caceres, O. Libiger, C. Barlow, N. J. Schork, and D. J. Lockhart (2007)
Genome Res. 17, 1228-1235
   Abstract »    Full Text »    PDF »
A Perspective on DNA Microarrays in Pathology Research and Practice.
J. R. Pollack (2007)
Am. J. Pathol. 171, 375-385
   Abstract »    Full Text »    PDF »
Immune Signatures of Murine and Human Cancers Reveal Unique Mechanisms of Tumor Escape and New Targets for Cancer Immunotherapy.
R. E. Sadun, S. M. Sachsman, X. Chen, K. W. Christenson, W. Z. Morris, P. Hu, and A. L. Epstein (2007)
Clin. Cancer Res. 13, 4016-4025
   Abstract »    Full Text »    PDF »
Personalized Medicine for High Blood Pressure.
S. T. Turner, G. L. Schwartz, and E. Boerwinkle (2007)
Hypertension 50, 1-5
   Full Text »    PDF »
High-Throughput, High-Sensitivity Analysis of Gene Expression in Arabidopsis.
R. M. Kris, S. Felder, M. Deyholos, G. M. Lambert, J. Hinton, I. Botros, R. Martel, B. Seligmann, and D. W. Galbraith (2007)
Plant Physiology 144, 1256-1266
   Abstract »    Full Text »    PDF »
Connecting the Dots Using Gene-Expression Profiles.
S. R. Gullans (2006)
N. Engl. J. Med. 355, 2042-2044
   Full Text »    PDF »

E-Letters:

Read all E-Letters

Bias in Favor of Connectivity Map
Abhay Sharma
Science Online, 8 Feb 2007 [Full text]
The Connectivity Map is Biased Towards Experimental Approach
Syed H. I. Abidi
Science Online, 18 Apr 2007 [Full text]
Response to E-Letter by Sharma
Todd R. Golub
Science Online, 22 Feb 2007 [Full text]
Re: Response to E-Letter by Golub
Abhay Sharma
Science Online, 18 Apr 2007 [Full text]

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)