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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks.

A major challenge in drug discovery is to distinguish the molecular targets of a bioactive compound from the hundreds to thousands of additional gene products that respond indirectly to changes in the activity of the targets. Here, we present an integrated computational-experimental approach for computing the likelihood that gene products and associated pathways are targets of a compound. This is achieved by filtering the mRNA expression profile of compound-exposed cells using a reverse-engineered model of the cell's gene regulatory network. We apply the method to a set of 515 whole-genome yeast expression profiles resulting from a variety of treatments (compounds, knockouts and induced expression), and correctly enrich for the known targets and associated pathways in the majority of compounds examined. We demonstrate our approach with PTSB, a growth inhibitory compound with a previously unknown mode of action, by predicting and validating thioredoxin and thioredoxin reductase as its target.[1]

References

  1. Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks. di Bernardo, D., Thompson, M.J., Gardner, T.S., Chobot, S.E., Eastwood, E.L., Wojtovich, A.P., Elliott, S.J., Schaus, S.E., Collins, J.J. Nat. Biotechnol. (2005) [Pubmed]
 
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