1/2 Discovery and validation of neuronal enhancers associated with the development of psychiatric disorders

项目概要/摘要 在这个项目中，我们将开发新的方法来寻找大脑特异性增强子，建立 调节网络，去卷积脑区域特异性调节，并将差异 增强子信号在人群中的变化。我们将应用这些分析 方法的psychENCODE数据语料库，将这些数据与GTEx，ENCODE， CommonMind数据，注释与精神疾病相关的GWAS SNP， 发现了用于验证的监管元素，并将所有psychENCODE数据可视化， 综合时尚然后，我们将验证这些预测的调控元件使用大规模的 神经母细胞瘤细胞、iPSC细胞和分化的神经元前体细胞的基因组测定 神经元谱系，并使用能够培养神经元细胞的微流体平台， 神经元类器官这些研究的结果将进一步加深我们对遗传学的理解。 正常和神经精神疾病状态下神经元功能的调节基础。

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.