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

1/2 与精神疾病发展相关的神经元增强剂的发现和验证

基本信息

批准号：
10377537
负责人：
Mark Bender Gerstein
金额：
$ 111.19万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-06 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377537
关键词：
3-Dimensional Adolescence Adult Affect Alleles Base Sequence Biological Biological Assay Brain Brain region Cell Differentiation process Cell model Cells Cerebrum Chromatin Clustered Regularly Interspaced Short Palindromic Repeats Communities Data Data Analyses Data Coordinating Center Data Set Development Disease Enhancers Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Genetic Polymorphism Genomic Segment Genomics Genotype-Tissue Expression Project Human Human Genome Individual Knock-out Link Measures Mental disorders Metadata Methodology Methods Microfluidic Microchips Microfluidics Modeling Network-based Neurons Online Systems Organoids Output Pattern Recognition Population Process Prosencephalon Protocols documentation Quantitative Trait Loci Regulation Regulatory Element Reporter Research Resources Series Signal Pathway Signal Transduction Specific qualifier value Technology Testing Tissues Validation Variant analytical method base cell type early childhood epigenomics fetal genetic variant genome browser genome wide association study genome-wide induced pluripotent stem cell machine learning framework neuroblastoma cell neuron development neuropsychiatric disorder novel precursor cell rapid testing single cell sequencing single-cell RNA sequencing stem cell differentiation transcriptome transcriptome sequencing

项目摘要

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.

项目摘要/摘要在这个项目中，我们将开发出新的方法来寻找大脑特异性增强剂，建造调节网络，对大脑区域特异性调节，并关联差异增强子信号对人口的变化。然后，我们将应用这些分析心理码数据语料库的方法，将这些数据与GTEX，ENCODE和共同数据，注释与心理疾病相关的GWAS SNP，优先考虑发现了用于验证的监管元素，并在综合时尚。然后，我们将使用大规模验证这些预测的调节元素神经母细胞瘤细胞，IPSC细胞和神经元前体细胞中的基因组测定分化进入神经元谱系，并使用能够培养神经元细胞和的微流体平台神经元类器官。这些研究的结果将进一步我们对遗传的理解在正常和神经精神疾病状态下神经元功能的调节基础。