Detecting synergistic effects of pharmacological and non-pharmacological interventions for AD/ADRD
Detecting synergistic effects of pharmacological and non-pharmacological interventions for AD/ADRD
批准号:
10501245
负责人:
HUA XU
金额:
$78.15万
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
项目状态:
未结题
起止时间:
2022-09-01 至 2027-05-31
关键词:
AerobicAerobic ExerciseAffectAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmericanAnimal ModelAnimalsAromatherapyBrain DiseasesClinical TrialsClinical Trials DesignCognitiveCognitive agingCollaborationsCommunitiesDataData SourcesDementiaDietDiseaseElderlyElectronic Health RecordEnvironmental Risk FactorGene TargetingGenetic RiskGoalsIndividualInformaticsInterventionKnowledgeLightLinkLiteratureMethodsMiningModelingNatural Language ProcessingNetwork-basedOntologyPharmaceutical PreparationsPharmacologyPhototherapyPreventionReportingResearchSignal TransductionSiteSleepStandardizationTranslatingValidationVisualizationWorkalternative treatmentclinical investigationcognitive trainingcomputerized toolsdata resourcedietarydietary supplementsdrug discoverydrug repurposingeffective therapyimprovedin silicoin vivoinnovationintervention effectknowledge baseknowledge graphmouse modelmultimodal datamultimodalityneural networknovelontology developmentpopulation basedpredictive modelingpreventsynergismtool
中文摘要
项目概要
阿尔茨海默病 (AD) 和相关痴呆 (AD/ADRD) 是一种多因素和异质性疾病。大多数
目前的研究重点是 AD/ADRD 的药物干预,目前还没有药物干预 (PI)
发现研究已转化为有效的治疗方法。然而,越来越多的证据表明
非药物干预(NPI),例如睡眠、饮食、膳食补充剂、有氧运动、
芳香疗法、光疗法、认知训练都是可以修改的,因此提供了替代机会
用于 AD/ADRD 预防。因此,该项目的目标是开发转化信息学方法
使用多模式汇总、标准化和发现药物和 NPI 候选药物对 AD/ADRD 的影响
数据资源(即生物医学文献、电子病历、临床试验),然后进行动物模型验证。达到
为了我们的目标,我们提出以下目标: 1)构建全面的药理学和非
生物医学文献中的阿尔茨海默病药理干预知识图谱 (PANIA-KG)
和其他知识库; 2) 检测、理解和可视化 PI 的药物再利用信号,
NPI 及其使用 PANIA-KG 对 AD/ADRD 的协同效应; 3)重新排名和验证个人
以及使用多模式数据源和动物模型的协同药物再利用信号。成功者
该项目的完成将提供全面的 NPI 知识图、新颖的信息学方法、
对候选药物和 NPI 进行排名,并使用多模式数据源验证协同干预。
生成的方法、PANIA-KG 和排名列表可以进一步促进我们的临床研究和临床试验
设计重点关注药物和 NPI 对 AD/ADRD 的协同作用。
英文摘要
PROJECT SUMMARY
Alzheimer's disease (AD) and related dementia (AD/ADRD) is a multifactorial and heterogeneous disorder. Most
current studies focus on drug interventions for AD/ADRD and currently none of pharmacological intervention (PI)
discovery research has been translated into effective treatments. However, increasing evidence demonstrates
that non-pharmacological interventions (NPI), such as sleep, diet, dietary supplements, aerobic exercise,
aromatherapy, light therapy, cognitive training, are potentially modifiable and thus offer alternative opportunities
for AD/ADRD prevention. Thus, the objective of this project is to develop translational informatics approaches to
aggregate, standardize and discover the effects of drug and NPI candidates on AD/ADRD using multi-modal
data resources (i.e., biomedical literature, EHR, clinical trials) followed by animal model validation. To achieve
our goal, we propose the following aims: 1) constructing a comprehensive Pharmacological And Non-
Pharmacological Interventions for Alzheimer's Disease Knowledge Graph (PANIA-KG) from biomedical literature
and other knowledge bases; 2) detecting, understanding, and visualization of drug repurposing signals of PIs,
NPIs, and their synergistical effects for AD/ADRD using the PANIA-KG; 3) re-ranking and validating individual
and synergistical drug repurposing signals using multimodal data sources and animal models. The successful
completion of this project will deliver a comprehensive NPI knowledge graph, novel informatics approaches,
ranked list of drug and NPI candidates, and validated synergistic intervention using multi-modal data sources.
The generated approaches, PANIA-KG and ranked lists can further our clinical investigations and clinical trial
design which focuses on synergistic effects of drug and NPIs for AD/ADRD.
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