Systematic Analysis of Drug Targets Confirms Expression in Disease-Relevant Tissues.
It is commonly assumed that drug targets are expressed in tissues relevant to their indicated diseases, even under normal conditions. While multiple anecdotal cases support this hypothesis, a comprehensive study has not been performed to verify it. We conducted a systematic analysis to assess gene and protein expression for all targets of marketed and phase III drugs across a diverse collection of normal human tissues. For 87% of gene-disease pairs, the target is expressed in a disease-affected tissue under healthy conditions. This result validates the importance of confirming expression of a novel drug target in an appropriate tissue for each disease indication and strengthens previous findings showing that targets of efficacious drugs should be expressed in relevant tissues under normal conditions. Further characterization of the remaining 13% of gene-disease pairs revealed that most genes are expressed in a different tissue linked to another disease. Our analysis demonstrates the value of extensive tissue specific expression resources.both in terms of tissue and cell diversity as well as techniques used to measure gene expression.
Computational Biology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Vinod
V
Kumar
Computational Biology, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Philippe
P
Sanseau
Computational Biology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Daniel F
DF
Simola
Computational Biology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Mark R
MR
Hurle
Computational Biology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Pankaj
P
Agarwal
D017326:Clinical Trials, Phase III as Topic; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D040901:Proteomics / Q000379:methods*