The connectivity map: Using gene-expression profiling to identify new therapeutics and potential adverse drug effects

TOXI 143

Justin Lamb, justin@broad.mit.edu, Broad Institute of MIT and Harvard, Seven Cambridge Center, Cambridge, MA 02142
Genome-wide transcriptional analysis provides a comprehensive molecular representation of cellular activity, suggesting that mRNA expression profiling could serve as a practical universal functional bioassay. High-throughput high-density gene-expression profiling solutions raise the possibility of capturing the consequences of small-molecule and genetic perturbations at library and genome scale, respectively, and associating these disparate perturbagens with each other and external organic phenotypes to discover decisive functional connections between drugs, genes and diseases. The talk will describe our technology platform, analysis methods and interpretive tools, and will include examples illustrating how the expression profiles of a large collection of bioactive small molecules can be used to reveal signaling cascades, annotate complex phenotypes, predict adverse drug effects, and identify potential human therapeutics.