New computational, transcriptional, and genome editing approaches to the biology of inflammatory bowel disease

研究炎症性肠病生物学的新计算、转录和基因组编辑方法

基本信息

  • 批准号:
    10200800
  • 负责人:
  • 金额:
    $ 17.27万
  • 依托单位:
  • 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:
    2018-09-19 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary Over the past decade, the NIDDK IBDGC (Inflammatory Bowel Disease Genetics Consortium) has generated extraordinary datasets in support of genetic analysis of the onset, progression, and therapeutic response to Crohn's disease and ulcerative colitis. This Ancillary project will complement ongoing IBDGC research by providing parallel statistical genetic analyses focused on transcriptomics, while also developing a novel strategy for genetic manipulation of patient-derived epithelial cells. There are four major biomedical genomics focus areas addressed by the research, namely fine mapping of loci influencing inflammatory bowel disease, elucidation of the cell and molecular function of causal genes, understanding how polymorphism influences pathology, and translating quantitative genetic discoveries into clinical outcomes. Specifically, integrative genomics expertise will be used to refine the credible intervals responsible for complex association signals at individual loci, enhance transcriptional risk scores (TRS) that have recently been shown to provide much greater prediction of disease and progression than genetic risk scores, and explore the potential of in silico predicted transcriptome-wide association studies in the context of IBD. These studies will utilize the IBDGC datasets through collaborative arrangements mediated by data coordinating center. In addition, proof of principle for the use of lipid nanoparticles as an efficient and specific delivery system for genome editing and/or pharmaceutical delivery to targeted cell types in gut- derived organoids will be demonstrated. Single cell RNA-Seq will be used to partition variability in gut epithelial gene expression in the half dozen most common organoid cell types into contributions of the ethnicity, location of the biopsy, type of disease, and source laboratory. This data will serve as a foundation for evaluating the effects of a half dozen gene knock-outs across cell types using the lipid nanoparticle delivery system. All analyses and reagents will be made available to consortium members as expected for collaborative IBDGC research.
项目摘要 在过去的十年中,NIDDK IBDGC(炎症性肠病遗传学联盟) 生成了非凡的数据集,以支持对发病、进展和治疗的遗传分析。 对克罗恩病和溃疡性结肠炎的反应。该辅助项目将补充正在进行的IBDGC 研究通过提供平行的统计遗传分析集中在转录组学,同时也发展 一种新的策略,用于遗传操作的患者来源的上皮细胞。有四大 生物医学基因组学的重点领域解决的研究,即基因座的精细映射影响 炎症性肠病,阐明致病基因的细胞和分子功能,理解 多态性如何影响病理学,并将定量遗传学发现转化为临床 结果。具体而言,将使用综合基因组学专业知识来完善可信区间 负责单个基因座的复杂关联信号,增强转录风险评分(TRS), 最近显示,与遗传风险相比, 评分,并探索在计算机模拟预测的转录组范围内的关联研究的潜力, IBD。这些研究将通过以数据为媒介的合作安排利用IBDGC数据集 协调中心。此外,使用脂质纳米颗粒作为一种有效的和有效的治疗方法的原理证明, 用于基因组编辑和/或药物递送到肠内靶向细胞类型的特异性递送系统, 将展示衍生的类器官。单细胞RNA-Seq将用于划分肠道中的变异性 上皮基因表达在半打最常见的类器官细胞类型的贡献, 种族、活检位置、疾病类型和源实验室。这些数据将作为基础 用于评估使用脂质纳米颗粒的六种基因敲除对细胞类型的影响, 输送系统。所有分析和试剂将按预期提供给联合体成员, IBDGC合作研究。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Canalization of the Polygenic Risk for Common Diseases and Traits in the UK Biobank Cohort.
  • DOI:
    10.1093/molbev/msac053
  • 发表时间:
    2022-04-11
  • 期刊:
  • 影响因子:
    10.7
  • 作者:
    Nagpal, Sini;Tandon, Raghav;Gibson, Greg
  • 通讯作者:
    Gibson, Greg
Integrative polygenic analysis of the protective effects of fatty acid metabolism on disease as modified by obesity.
  • DOI:
    10.3389/fnut.2023.1308622
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    5
  • 作者:
    Astore, Courtney;Gibson, Greg
  • 通讯作者:
    Gibson, Greg
Perspectives on rigor and reproducibility in single cell genomics.
  • DOI:
    10.1371/journal.pgen.1010210
  • 发表时间:
    2022-05
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
  • 通讯作者:
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GREGORY C GIBSON其他文献

GREGORY C GIBSON的其他文献

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{{ truncateString('GREGORY C GIBSON', 18)}}的其他基金

New computational, transcriptional, and genome editing approaches to the biology of inflammatory bowel disease
研究炎症性肠病生物学的新计算、转录和基因组编辑方法
  • 批准号:
    9976502
  • 财政年份:
    2018
  • 资助金额:
    $ 17.27万
  • 项目类别:
eQTL mega-analysis for functional assessment of multi-enhancer gene regulation
用于多增强子基因调控功能评估的 eQTL 大分析
  • 批准号:
    9330894
  • 财政年份:
    2016
  • 资助金额:
    $ 17.27万
  • 项目类别:
eQTL mega-analysis for functional assessment of multi-enhancer gene regulation
用于多增强子基因调控功能评估的 eQTL 大分析
  • 批准号:
    9072104
  • 财政年份:
    2016
  • 资助金额:
    $ 17.27万
  • 项目类别:
A Computational Biology and Predictive Health Genomics Training Program at GT
GT 的计算生物学和预测健康基因组学培训项目
  • 批准号:
    9285807
  • 财政年份:
    2014
  • 资助金额:
    $ 17.27万
  • 项目类别:
A Computational Biology and Predictive Health Genomics Training Program at GT
GT 的计算生物学和预测健康基因组学培训项目
  • 批准号:
    8473373
  • 财政年份:
    2014
  • 资助金额:
    $ 17.27万
  • 项目类别:
DROSOPHILA PHARMACOGENETICS
果蝇药物遗传学
  • 批准号:
    6830214
  • 财政年份:
    2003
  • 资助金额:
    $ 17.27万
  • 项目类别:
QUANTITATIVE GENETIC ANALYSIS OF SIGNAL TRANSDUCTION
信号转导的定量遗传分析
  • 批准号:
    6630485
  • 财政年份:
    2000
  • 资助金额:
    $ 17.27万
  • 项目类别:
QUANTITATIVE GENETIC ANALYSIS OF SIGNAL TRANSDUCTION
信号转导的定量遗传分析
  • 批准号:
    6525921
  • 财政年份:
    2000
  • 资助金额:
    $ 17.27万
  • 项目类别:
Quantitative Genetic Analysis of Signal Transduction
信号转导的定量遗传分析
  • 批准号:
    6924864
  • 财政年份:
    2000
  • 资助金额:
    $ 17.27万
  • 项目类别:
Quantitative Genetic Analysis of Signal Transduction
信号转导的定量遗传分析
  • 批准号:
    7025823
  • 财政年份:
    2000
  • 资助金额:
    $ 17.27万
  • 项目类别:

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