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

Science. 2006 Sep 29;313(5795):1929-35. doi: 10.1126/science.1132939.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Cell Line
  • Cell Line, Tumor
  • Databases, Factual*
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Drug Evaluation, Preclinical / methods*
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / pharmacology
  • Estrogens / pharmacology
  • Gene Expression / drug effects*
  • Gene Expression Profiling*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • Histone Deacetylase Inhibitors
  • Humans
  • Limonins / pharmacology
  • Obesity / genetics
  • Obesity / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Phenothiazines / pharmacology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / physiopathology
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • Software

Substances

  • Enzyme Inhibitors
  • Estrogens
  • HSP90 Heat-Shock Proteins
  • Histone Deacetylase Inhibitors
  • Limonins
  • Phenothiazines
  • gedunin
  • Dexamethasone
  • Sirolimus