Mechanism-guided drug repurposing for host-directed therapy of infectious diseases using interpretable and integrative ML

使用可解释和集成的机器学习机制引导的药物再利用,用于针对宿主的传染病治疗

基本信息

  • 批准号:
    10619589
  • 负责人:
  • 金额:
    $ 18.18万
  • 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:
    2022-05-09 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

ABSTRACT Our ability to treat infectious diseases is impeded by two major problems. One is the rapid increase of antimicrobial resistance, and the other is the prohibitive cost and time required for discovering new drugs. A potential approach to overcome these problems is to focus on repurposing existing drugs for host-directed therapy. However, this is an emerging application area. While several studies have used this broad approach to find drug candidates for specific viruses and bacterial infections, there is a dearth of systematic computational frameworks that can be used to repurpose drugs for any infectious disease, especially ones that focus on drug and disease mechanisms rather than individual drug and target properties. Also missing are frameworks that can leverage the massive amounts of data and knowledge available for non-infectious diseases to tackle infectious disease treatment. In this project, we will develop an integrative framework that uses mechanism- guided, interpretable machine learning (ML) models to repurpose drugs to bolster host response to infection. Our framework leverages massive transcriptome data collections and genome-scale human gene interaction networks; these are two complementary sources of information about molecular mechanisms relevant for this repurposing effort. It also uses data and knowledge about hundreds of non-infectious diseases and thousands of small molecules (including FDA-approved drugs) to create numerous repurposing opportunities. Requiring only host transcriptome data in response to infection, our general-purpose ML framework will be applicable to new, emerging, and understudied infectious diseases. This project will also result in high-confidence drug candidates for several infectious diseases along with mechanistic insights into new avenues for host-directed therapeutics.
摘要 我们治疗传染病的能力受到两个主要问题的阻碍。一是快速增长的 抗生素耐药性,另一个是发现新药所需的高昂成本和时间。一 克服这些问题的潜在方法是专注于将现有药物重新用于宿主定向 疗法这是一个新兴的应用领域。虽然有几项研究使用了这种广泛的方法, 寻找特定病毒和细菌感染的候选药物,缺乏系统的计算能力。 这些框架可用于重新使用药物治疗任何传染病,特别是那些专注于药物治疗的框架。 和疾病机制,而不是单个药物和靶标特性。同样缺少的是框架, 可以利用非传染性疾病的大量数据和知识, 传染病治疗。在这个项目中,我们将开发一个综合框架,使用机制- 引导,可解释的机器学习(ML)模型,以重新使用药物来增强宿主对感染的反应。 我们的框架利用了大量的转录组数据收集和基因组规模的人类基因相互作用 网络;这是关于与此相关的分子机制的两个互补信息来源。 再利用的努力。它还使用了数百种非传染性疾病和数千种 小分子药物(包括FDA批准的药物),以创造大量的再利用机会。要求 只有主机转录组数据响应感染,我们的通用ML框架将适用于 新的、正在出现的和未充分研究的传染病。该项目还将产生高置信度药物 候选人的几种传染病沿着与机制的见解,新的途径,为主机导向 治疗学

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Arjun Krishnan其他文献

Arjun Krishnan的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Arjun Krishnan', 18)}}的其他基金

Mechanism-guided drug repurposing for host-directed therapy of infectious diseases using interpretable and integrative ML
使用可解释和集成的机器学习机制引导的药物再利用,用于针对宿主的传染病治疗
  • 批准号:
    10738676
  • 财政年份:
    2022
  • 资助金额:
    $ 18.18万
  • 项目类别:
Mechanism-guided drug repurposing for host-directed therapy of infectious diseases using interpretable and integrative ML
使用可解释和集成的机器学习机制引导的药物再利用,用于针对宿主的传染病治疗
  • 批准号:
    10442808
  • 财政年份:
    2022
  • 资助金额:
    $ 18.18万
  • 项目类别:
Resolving and understanding the genomic basis of heterogeneous complex traits and diseases
解决和理解异质复杂性状和疾病的基因组基础
  • 批准号:
    10406616
  • 财政年份:
    2018
  • 资助金额:
    $ 18.18万
  • 项目类别:
Resolving and understanding the genomic basis of heterogeneous complex traits and disease
解决和理解异质复杂性状和疾病的基因组基础
  • 批准号:
    9764395
  • 财政年份:
    2018
  • 资助金额:
    $ 18.18万
  • 项目类别:
Resolving and understanding the genomic basis of heterogeneous complex traits and disease
解决和理解异质复杂性状和疾病的基因组基础
  • 批准号:
    10226291
  • 财政年份:
    2018
  • 资助金额:
    $ 18.18万
  • 项目类别:
Resolving and understanding the genomic basis of heterogeneous complex traits and disease
解决和理解异质复杂性状和疾病的基因组基础
  • 批准号:
    10700497
  • 财政年份:
    2018
  • 资助金额:
    $ 18.18万
  • 项目类别:

相似海外基金

Cerebral infarction treatment strategy using collagen-like "triple helix peptide" containing functional amino acid sequence
含功能氨基酸序列的类胶原“三螺旋肽”治疗脑梗塞策略
  • 批准号:
    23K06972
  • 财政年份:
    2023
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Establishment of a screening method for functional microproteins independent of amino acid sequence conservation
不依赖氨基酸序列保守性的功能性微生物蛋白筛选方法的建立
  • 批准号:
    23KJ0939
  • 财政年份:
    2023
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Effects of amino acid sequence and lipids on the structure and self-association of transmembrane helices
氨基酸序列和脂质对跨膜螺旋结构和自缔合的影响
  • 批准号:
    19K07013
  • 财政年份:
    2019
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Construction of electron-transfer amino acid sequence probe with an interaction for protein and cell
蛋白质与细胞相互作用的电子转移氨基酸序列探针的构建
  • 批准号:
    16K05820
  • 财政年份:
    2016
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of artificial antibody of anti-bitter taste receptor using random amino acid sequence library
利用随机氨基酸序列库开发抗苦味受体人工抗体
  • 批准号:
    16K08426
  • 财政年份:
    2016
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The aa15-17 amino acid sequence in the terminal protein domain of HBV polymerase as a viral factor affect-ing in vivo as well as in vitro replication activity of the virus.
HBV聚合酶末端蛋白结构域中的aa15-17氨基酸序列作为影响病毒体内和体外复制活性的病毒因子。
  • 批准号:
    25461010
  • 财政年份:
    2013
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Amino acid sequence analysis of fossil proteins using mass spectrometry
使用质谱法分析化石蛋白质的氨基酸序列
  • 批准号:
    23654177
  • 财政年份:
    2011
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Precise hybrid synthesis of glycoprotein through amino acid sequence-specific introduction of oligosaccharide followed by enzymatic transglycosylation reaction
通过氨基酸序列特异性引入寡糖,然后进行酶促糖基转移反应,精确杂合合成糖蛋白
  • 批准号:
    22550105
  • 财政年份:
    2010
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Estimating selection on amino-acid sequence polymorphisms in Drosophila
果蝇氨基酸序列多态性选择的估计
  • 批准号:
    NE/D00232X/1
  • 财政年份:
    2006
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Research Grant
Construction of a neural network for detecting novel domains from amino acid sequence information only
构建仅从氨基酸序列信息检测新结构域的神经网络
  • 批准号:
    16500189
  • 财政年份:
    2004
  • 资助金额:
    $ 18.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了