In this supplement to our ENCODE4 project, we will analyze functional genomics data from up to 7 major brain regions in Alzheimer?s Disease (AD) patients and healthy controls. These data include both bulk tissue and single cell assays. We will use these data to generate brain cell-type specific regulatory maps in AD cases and controls, and to understand the processes of dysregulation in AD. We will additionally use these data, supplemented with public data, to identify critical cell types for AD progression, causal variants, target genes and regulatory networks in AD cases and controls. Finally, we will validate regulatory variants using MPRAs and CRISPR experiments in induced pluripotent stem cell-derived neurons. In summary, this supplement will enable us to provide high-resolution maps of chromatin function and healthy and diseased brains, and to link disease-associated variants to likely functional roles.
The purpose of this supplemental project is to apply powerful new computational and functional genomics methods to identify causal cell types, genes and variants in Alzheimer?s disease (AD). Outputs from the project will include a chromatin accessibility map of AD across brain regions and functional fine-mapping and validation of regulatory variants in AD.
