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

在这个项目中，我们将开发新的方法来寻找大脑特定的增强剂，建立 调节网络，解除大脑区域特定的调节，并与差异相关 增强子向人类种群的变异发出信号。然后我们将应用这些分析 方法，将这些数据与GTEX、ENCODE和 CommonMind数据，注释与精神疾病相关的GWASNPs，优先 发现了用于验证的监管元素，并在 综合时尚。然后，我们将使用大规模数据验证这些预测的监管要素 神经母细胞瘤细胞、IPSC细胞和神经前体细胞分化的基因组分析 转化为神经细胞，并使用微流体平台能够培养神经元细胞和 神经元器官。这些研究的结果将加深我们对基因的理解 神经功能在正常和神经精神疾病状态下的调节基础。

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.