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CIRCUITS: Utilizing Functional Maps to Prioritize Therapeutic Targets in Alzheimer’s Disease

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Discovery of the causes of and treatment for Alzheimer’s is confounded by the complexity of the disease, the interplay between environment and genetic bases of disease and the disparate approaches taken by groups to look at specific aspects of the disease. Progress has been slow and there is an urgent need to deliver treatments that are effective and have few side effects. Current studies seek specific genes as treatment targets. Usually there is a strong bias by a single group as to which genes and processes they think are responsible for the disease. Failure rates are high.

This consortium generates many different types of high dimensional omics data and integrates them together in an unbiased manner to systematically and objectively deliver the key processes and genes that appear to be responsible for the onset and progression of the disease. Using an existing Industry-sponsored model pioneered at the Sheffield Centre for Genome Translation, this proposal coordinates the data being generated by the consortium, and ingests these disparate data—and the key genes and pathways resulting from them—to objectively rank the genes and pathways by their likely impact on the disease. In turn, ranked pathways then are matched for their suitability for targeting by existing drugs. The resulting drug/pathway/gene models will provide invaluable reagents for industry and academia to assess in terms of their direct clinical outcomes on Alzheimer’s treatment and progression.