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Quantitative systems-level determinants of human genes targeted by successful drugs Yao L; Rzhetsky AGenome Res 2008[Feb]; 18 (2): 206-13What makes a successful drug target? A target molecule with an appropriate (druggable) tertiary structure is a necessary but not the sufficient condition for success. Here we analyzed specific properties of human genes and proteins targeted by 919 FDA-approved drugs and identified several quantitative measures that distinguish them from other genes and proteins at a highly significant level. Compared to an average gene and its encoded protein(s), successful drug targets are more highly connected (but far from being the most highly connected), have higher betweenness values, lower entropies of tissue expression, and lower ratios of nonsynonymous to synonymous single-nucleotide polymorphisms. Furthermore, we have identified human tissues that are significantly over- or undertargeted relative to the full spectrum of genes that are active in each tissue. Our study provides quantitative guidelines that could aid in the computational screening of new drug targets in human cells.|*Gene Expression Profiling[MESH]|Drug Delivery Systems/*methods/trends[MESH]|Genes/*genetics[MESH]|Humans[MESH]|Models, Theoretical[MESH]|Polymorphism, Single Nucleotide/genetics[MESH]|Proteins/*genetics/metabolism[MESH] |
