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The druggable genome and support for target identification and validation in drug development
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The druggable genome and support for target identification and validation in drug development
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Paper
The druggable genome and support for target identification and validation in drug development
2016
Overview
Target identification (identifying the correct drug targets for each disease) and target validation (demonstrating the effect of target perturbation on disease biomarkers and disease end-points) are essential steps in drug development. We showed previously that biomarker and disease endpoint associations of single nucleotide polymorphisms (SNPs) in a gene encoding a drug target accurately depict the effect of modifying the same target with a pharmacological agent; others have shown that genomic support for a target is associated with a higher rate of drug development success. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome wide association studies (GWAS) to an updated set of genes encoding druggable human proteins, to compounds with bioactivity against these targets and, where these were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, to enable druggable genome-wide association studies for drug target selection and validation in human disease.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
