The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.
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.
Lamb
Justin
J
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. justin@broad.mit.edu
Crawford
Emily D
ED
Peck
David
D
Modell
Joshua W
JW
Blat
Irene C
IC
Wrobel
Matthew J
MJ
Lerner
Jim
J
Brunet
Jean-Philippe
JP
Subramanian
Aravind
A
Ross
Kenneth N
KN
Reich
Michael
M
Hieronymus
Haley
H
Wei
Guo
G
Armstrong
Scott A
SA
Haggarty
Stephen J
SJ
Clemons
Paul A
PA
Wei
Ru
R
Carr
Steven A
SA
Lander
Eric S
ES
Golub
Todd R
TR
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D016208:Databases, Factual; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D036701:Limonins / Q000494:pharmacology; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D010640:Phenothiazines / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D012984:Software
D004791:Enzyme Inhibitors; D004967:Estrogens; D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D036701:Limonins; D010640:Phenothiazines; C106014:gedunin; D003907:Dexamethasone; D020123:Sirolimus