Approaches to target identification, prioritization and drug repurposing

Drug repurposing, the use of existing drugs for new indications, is a cost effective and expeditious complement to traditional drug discovery. This is especially important in areas such as rare diseases where significant unmet need can be identified. Despite 7% of the population suffering from a rare disease, only a minority of rare diseases have an approved medication. The 100,000 Genomes Project (100KGP, also referred to as GEL in reference to it's operating company, Genomics England) is a UK government funded project, completed in October 2017, in which 87,000 people were sequenced. This project predominantly recruited rare disease patients and their close family members such that novel disease causing variants could be identified. The aim of this PhD is to use data associated with the 100KGP and other public resources to identify targets for therapeutic intervention, and subsequently rank them based on various other features. Chief amongst these is the loss of function characteristics of the target, and what can be inferred about target safety based on these data.