Mapping Biological Connectivity

Science's STKE  03 Oct 2006:
Vol. 2006, Issue 355, pp. tw343
DOI: 10.1126/stke.3552006tw343

Comprehensive catalogs of biological information (such as sequence or protein structure data) can have enormous utility in biomedical research. Lamb et al. have extended this approach to create comprehensive catalogs of cellular states, as defined by RNA expression. The effects of 164 small molecules on the complete messenger RNA expression profiles were examined in established cell lines, with a primary focus on a breast cancer epithelial cell line. By comparing the genomic signature of drug candidates (the anticancer drug gedunin, estrogen, histone deacetylase, and phenothiazine antipyschotics) or a disease state (obesity, Alzheimer’s disease, and dexamethasone-resistant acute lymphoblastic leukemia) to this resource, it was possible to identify potential mechanisms of action, confirm previous applications of known drugs, and identify additional potential uses for known drugs.

J. Lamb, E. D. Crawford, D. Peck, J. W. Modell, I. C. Blat, M. J. Wrobel, J. Lerner, J.-P. Brunet, A. Subramanian, K. N. Ross, M. Reich, H. Hieronymus, G. Wei, S. A. Armstrong, S. J. Haggarty, P. A. Clemons, R. Wei, S. A. Carr, E. S. Lander, T. R. Golub, The connectivity map: Using gene-expression signatures to connect small molecules, genes, and disease. Science 313, 1929-1935 (2006). [Abstract] [Full Text]