Project Summary/Abstract In this project, we will develop novel methods for finding brain-specific enhancers, build regulatory networks, deconvolve brain-region-specific regulation, and relate differential enhancer signals to variations in the human population. We will then apply these analytical methods to the psychENCODE data corpus, integrating these data with GTEx, ENCODE, and CommonMind data, annotating GWAS SNPs associated with psych disease, prioritizing the discovered regulatory elements for validation, and visualizing all psychENCODE data in an integrated fashion. We will then validate these predicted regulatory elements using large-scale genomic assays in neuroblastoma cells, iPSC cells, and neuronal precursor cells differentiated into neuronal lineages, and using a microfluidics platform capable of culturing neuronal cells and neuronal organoids. The results from these studies will further our understanding of the genetic regulatory basis for neuronal function in both normal and neuropsychiatric disease states.

Project Narrative The data generated by the psychENCODE Consortium are a pre-eminent, centralized resource for studying the human brain. We will develop cutting-edge analytical methods and apply them to the psychENCODE data corpus to identify regulatory elements and then validate them using large-scale genomic assays in neuronal cells and organoids. Our results will further our understanding of the human brain in the healthy state and neuropsychiatric diseases.