The human genome and drug discovery after a decade. Roads (still) not taken

The draft sequence of the human genome became available almost a decade ago but the encoded proteome is not being explored to its fullest. Our bibliometric analysis of several large protein families, including those known to be "druggable", reveals that, even today, most papers focus on proteins that were known prior to 2000. It is evident that one or more aspects of the biomedical research system severely limits the exploration of the proteins in the 'dark matter' of the proteome, despite unbiased genetic approaches that have pointed to their functional relevance. It is perhaps not surprising that relatively few genome-derived targets have led to approved drugs.