The transcriptome's drugable frequenters.
Microarray studies are widely employed in the exploratory phase of the drug discovery process. Expectations raised by the genomics revolution led to the belief that they would rapidly lead to the identification of novel drug targets. However, a few basic questions were often overlooked. Are members of drugable gene families properly represented in the transcriptome? Or are they poorly expressed and below the detection limit of the microarray technology? This review explores the representation of drug targets and components of downstream cellular signaling pathways in the transcriptome. It appears that members of drugable gene families are underrepresented in the transcriptomes of non-pathological human tissues. But, they are represented at or above the expected frequency in the differential transcriptome (i.e. the set of genes that changes expression upon a change in cellular environment). Analysis of differential gene expression on a genome-wide scale will therefore give a comprehensive overview of cellular pathways and possible drug targets.
Dechering
Koen J
KJ
N.V. Organon, Department of Target Discovery, Room RE2106, PO Box 20, 5340 BH Oss, The Netherlands. koen.dechering@organon.com
D015195:Drug Design; D020869:Gene Expression Profiling; D005787:Gene Frequency; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D015398:Signal Transduction; D014158:Transcription, Genetic
D020543:Proteome