Compound repositioning for Alzheimer's Disease using knowledge graphs, insurance claims data, and gene expression complementarity

使用知识图、保险索赔数据和基因表达互补性对阿尔茨海默病进行复合重新定位

基本信息

  • 批准号:
    10338152
  • 负责人:
  • 金额:
    $ 88.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-15 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY This proposal focuses on the challenge of identifying drug repositioning candidates for Alzheimer’s Disease. The foundation of this work is the ReFRAME library, a set of ~13,000 compounds that includes nearly all small molecules that have been FDA-approved, reached clinical development, or undergone significant preclinical profiling. The ReFRAME library is being actively screened against a diverse cross-section of in vitro assays. This proposal pursues three distinct strategies for identifying repositioning candidates among the ReFRAME collection. First, we will create and mine a large and heterogeneous biomedical knowledge graph. We will use machine learning methods to identify repositioning candidates based on properties of the knowledge graph surrounding and joining each drug and disease. Second, we will mine a massive data set of insurance claims data for associations between drug use and the incidence or severity of Alzheimer’s Disease. Containing almost 7 billion medical claims and over 2 billion pharmacy claims, this data set represents the largest source of claims data available. Third, we will use concept of gene expression complementarity to identify repositioning candidates. We will generate a gene expression signature for every ReFRAME compound in three cell lines relevant to Alzheimer’s Disease, and we will screen for compounds that produce a signature that appear to reverse gene expression changes seen in Alzheimer’s Disease. After assembling repositioning candidates identified through all three of these methods, we will prioritize up to 100 compounds (or compound combinations) for further characterization and validation. These follow-up experiments will initially investigate the activity of these compounds in five cell-based assays to establish a mechanistic hypothesis on their mechanism of action in Alzheimer’s Disease. Secondary follow-up experiments may include validation in some combination of in vitro (including hiPSC-derived cerebrocortical neurons and/or organoids) and in vivo systems. We believe that the multifaceted approach described in this proposal offers the best possible chance at successfully identifying AD repositioning candidates. Moreover, this work will create methods and resources that will be useful to the broader scientific community, both for Alzheimer’s Disease and for other disease areas.
项目总结

项目成果

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ANDREW I SU其他文献

ANDREW I SU的其他文献

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{{ truncateString('ANDREW I SU', 18)}}的其他基金

BioThings Explorer: A platform for distributed knowledge integration across biomedical APIs
BioThings Explorer:跨生物医学 API 的分布式知识集成平台
  • 批准号:
    10705399
  • 财政年份:
    2020
  • 资助金额:
    $ 88.65万
  • 项目类别:
BioThings Explorer: A platform for distributed knowledge integration across biomedical APIs
BioThings Explorer:跨生物医学 API 的分布式知识集成平台
  • 批准号:
    10056577
  • 财政年份:
    2020
  • 资助金额:
    $ 88.65万
  • 项目类别:
BioThings Explorer: A platform for distributed knowledge integration across biomedical APIs
BioThings Explorer:跨生物医学 API 的分布式知识集成平台
  • 批准号:
    10333462
  • 财政年份:
    2020
  • 资助金额:
    $ 88.65万
  • 项目类别:
BioThings Explorer: A platform for distributed knowledge integration across biomedical APIs
BioThings Explorer:跨生物医学 API 的分布式知识集成平台
  • 批准号:
    10547977
  • 财政年份:
    2020
  • 资助金额:
    $ 88.65万
  • 项目类别:
Compound repositioning for Alzheimer's Disease using knowledge graphs, insurance claims data, and gene expression complementarity
使用知识图、保险索赔数据和基因表达互补性对阿尔茨海默病进行复合重新定位
  • 批准号:
    10554439
  • 财政年份:
    2020
  • 资助金额:
    $ 88.65万
  • 项目类别:
Consortium for Viral Systems Biology Data Management and Bioinformatics Core
病毒系统生物学数据管理和生物信息学核心联盟
  • 批准号:
    10310602
  • 财政年份:
    2018
  • 资助金额:
    $ 88.65万
  • 项目类别:
Consortium for Viral Systems Biology Data Management and Bioinformatics Core
病毒系统生物学数据管理和生物信息学核心联盟
  • 批准号:
    10248830
  • 财政年份:
    2018
  • 资助金额:
    $ 88.65万
  • 项目类别:
Consortium for Viral Systems Biology Data Management and Bioinformatics Core
病毒系统生物学数据管理和生物信息学核心联盟
  • 批准号:
    10374716
  • 财政年份:
    2018
  • 资助金额:
    $ 88.65万
  • 项目类别:
Consortium for Viral Systems Biology Data Management and Bioinformatics Core
病毒系统生物学数据管理和生物信息学核心联盟
  • 批准号:
    10579083
  • 财政年份:
    2018
  • 资助金额:
    $ 88.65万
  • 项目类别:
Gene Wiki: expanding the ecosystem of community-intelligence resources
Gene Wiki:扩大社区情报资源的生态系统
  • 批准号:
    8891444
  • 财政年份:
    2010
  • 资助金额:
    $ 88.65万
  • 项目类别:

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  • 批准号:
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    30960334
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    2009
  • 资助金额:
    22.0 万元
  • 项目类别:
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Pathophysiological mechanisms of hypoperfusion in mouse models of Alzheimer?s disease and small vessel disease
阿尔茨海默病和小血管疾病小鼠模型低灌注的病理生理机制
  • 批准号:
    10657993
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    10531959
  • 财政年份:
    2022
  • 资助金额:
    $ 88.65万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10700991
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患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
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