Prediction and Validation of Oligodendrocyte Gene Regulatory Network from Multi-Omics

多组学预测和验证少突胶质细胞基因调控网络

基本信息

  • 批准号:
    10509768
  • 负责人:
  • 金额:
    $ 40.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT ABSTRACT Studies of several Intellectual/Developmental Disability (IDD) conditions have implicated white matter alterations in their pathogenesis, and mouse models of oligodendrocyte defects have validated mechanistic connections with cognitive disorders. In addition, many genetic causes of leukodystrophies have been identified, including mutations affecting the PLP1 gene in Pelizaeus-Merzbacher disease. However, due to the lack of tools to interpret significant variations in the noncoding genome, the ultimate influence of most genetic variants unfortunately remain uncharacterized. With the resources of PsychEncode and GTEx, a number of tools have emerged that can be integrated to create a network model of Transcription Factors (TFs) and their binding sites (TFBS), and several relevant datasets of the oligodendrocyte epigenome have emerged. The goal of this proposal is to integrate these epigenomic resources with newly available eQTL resources to develop a model that will improved predictive value in deciphering Whole Genome Sequencing (WGS) data from patients with a variety of developmental disabilities related to white matter changes. Along with creating the model, we will integrate motif analysis of known TFs involved in oligodendrocyte development (MYRF, SOX10, OLIG2, TCF4 and CHD7/8) to determine if variants alter transcription factor binding sites (TFBS) in oligodendrocyte-expressed genes. We anticipate that creation an improved oligodendrocyte GRN will lead to collaborative grant collaborations in several IDD conditions, such as Autism Spectrum Disorder (ASD), to elucidate the effects of noncoding changes in WGS and link them to perturbations in the oligodendrocyte network.
项目摘要 对几种智力/发育障碍(IDD)状况的研究表明,白色 在其发病机制中的物质改变,以及少突胶质细胞缺陷的小鼠模型, 与认知障碍的机械联系。此外,许多遗传因素 已经鉴定了脑白质营养不良,包括影响PLP 1基因的突变, Pelizaeus-Merzbacher病然而,由于缺乏工具来解释显着 非编码基因组的变异,大多数遗传变异的最终影响 不幸的是,仍然没有特征。借助PsychEncode和GTEx的资源, 已经出现了许多工具,可以集成这些工具来创建转录因子的网络模型 (TFs)及其结合位点(TFBS),以及少突胶质细胞的几个相关数据集 表观基因组已经出现。这项提案的目标是整合这些表观基因组资源 利用新的eQTL资源开发一个模型, 解读来自患有各种疾病的患者的全基因组测序(WGS)数据, 与白色物质变化有关的发育障碍。沿着创建模型,我们 将整合参与少突胶质细胞发育的已知TF的基序分析(MYRF, S 0X 10、0 LIG 2、TCF 4和CHD 7/8)以确定变体是否改变转录因子结合 少突胶质细胞表达基因中的TFBS位点。我们希望创造一个更好的 少突胶质细胞GRN将导致在几种IDD条件下的合作赠款合作, 如自闭症谱系障碍(ASD),以阐明非编码变化的影响, 并将它们与少突胶质细胞网络的扰动联系起来。

项目成果

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John P Svaren其他文献

John P Svaren的其他文献

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{{ truncateString('John P Svaren', 18)}}的其他基金

Creation of a Schwann Cell Gene Regulatory Network
雪旺细胞基因调控网络的创建
  • 批准号:
    10581647
  • 财政年份:
    2022
  • 资助金额:
    $ 40.1万
  • 项目类别:
IDD Models Core
IDD 模型核心
  • 批准号:
    10678933
  • 财政年份:
    2021
  • 资助金额:
    $ 40.1万
  • 项目类别:
IDD Models Core
IDD 模型核心
  • 批准号:
    10239780
  • 财政年份:
    2021
  • 资助金额:
    $ 40.1万
  • 项目类别:
IDD Models Core
IDD 模型核心
  • 批准号:
    10450732
  • 财政年份:
    2021
  • 资助金额:
    $ 40.1万
  • 项目类别:
Epigenetic Regulation of Nerve Injury
神经损伤的表观遗传调控
  • 批准号:
    9396615
  • 财政年份:
    2017
  • 资助金额:
    $ 40.1万
  • 项目类别:
Epigenetic Regulation of Nerve Injury
神经损伤的表观遗传调控
  • 批准号:
    10207795
  • 财政年份:
    2017
  • 资助金额:
    $ 40.1万
  • 项目类别:
Regulation of PMP22 Expression in Peripheral Nerve
周围神经中 PMP22 表达的调节
  • 批准号:
    9293380
  • 财政年份:
    2014
  • 资助金额:
    $ 40.1万
  • 项目类别:
Regulation of PMP22 Expression in Peripheral Nerve
周围神经中 PMP22 表达的调节
  • 批准号:
    9069615
  • 财政年份:
    2014
  • 资助金额:
    $ 40.1万
  • 项目类别:
Regulation of PMP22 Expression in Peripheral Nerve
周围神经中 PMP22 表达的调节
  • 批准号:
    8759907
  • 财政年份:
    2014
  • 资助金额:
    $ 40.1万
  • 项目类别:
Epigenetic Regulation of Peripheral Nerve Myelination
周围神经髓鞘形成的表观遗传调控
  • 批准号:
    8575660
  • 财政年份:
    2013
  • 资助金额:
    $ 40.1万
  • 项目类别:

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