Big data screening for associations between medication use and ALS
大数据筛选药物使用与 ALS 之间的关联
基本信息
- 批准号:9233275
- 负责人:
- 金额:$ 23.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-15 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAge of OnsetAmericanAmyotrophic Lateral SclerosisAttentionBig DataBiologicalClinical TrialsCombination MedicationComplexDataData SetDatabasesDenmarkDiseaseDrug CompoundingElderlyEpidemiologyEtiologyFaceGeneticGoalsHealthHealth systemIn VitroIncidenceIndividualInvestigationIsraelLaboratory ResearchLogicNeurodegenerative DisordersOutcomePatientsPharmaceutical PreparationsPharmacologic SubstancePopulationPrevalenceProbabilityProcessRegistriesResearchRiluzoleRiskRoleSurvival AnalysisSystemTestingTherapeuticTherapeutic EffectTherapeutic InterventionTherapeutic UsesTimeToxicologyVariantWorkbasebiological systemscase controlclinical phenotypedesignepidemiologic dataepidemiology studyforesthealth datahigh dimensionalityhigh throughput screeninginsightnon-geneticnovelnovel therapeuticsprospectivescreeningtransmission process
项目摘要
PROJECT SUMMARY/ABSTRACT
Our long-term goal is to identify medications, or combinations of medications, that may affect incidence of
amyotrophic lateral sclerosis (ALS) or alter the progression of ALS. In vitro efforts to exploring single
compounds for efficacy in ALS therapeutics based on proposed biological mechanisms for the disease is a
valuable and warranted approach, but it is inherently slow because of the need to test compounds one at a
time. It also does not explore effects of combinations and it cannot test the role of these compounds in ALS
incidence. Given the wide array of medications that older adults take, and the possibility that different
combinations of medications may be relevant, we propose that a valuable parallel approach would be an
epidemiological screening process to test whether any currently used medications are related to ALS incidence
or survival. This would be akin to in vitro high throughput screening, but using novel statistical approaches to
explore high dimensional “big” epidemiological data (many people, many medications) for associations with
ALS and ALS survival: specifically, boolean logic regression and random forests in a nested case-control and
survival analysis framework. These approaches allow for efficiently exploring high-dimensional, likely
correlated, data for associations between individual medications and different combinations of medications and
an outcome, here ALS. In order to accomplish this, we propose to use two parallel very large data sets with
prospectively and objectively collected pharmaceutical and health data: The Danish Registry System and the
Clalit Health System in Israel, with a total of approximately 4,300 ALS cases and over 300,000 controls. By
using the two data sets in different populations we will increase the probability of identifying causally related
compounds by identifying those that screen positive in both populations. The results of this work have the
possibility to identify currently used medications or combinations of these medications that can affect ALS and
survival with ALS. Any positive results could open up new research avenues that include targeted clinical trials
as well as potentially new directions for epidemiological studies and laboratory research into underlying
mechanisms.
项目总结/摘要
我们的长期目标是确定可能影响发生率的药物或药物组合,
肌萎缩侧索硬化症(ALS)或改变ALS的进展。在体外努力探索单一
基于所提出的疾病的生物学机制的用于ALS治疗的功效的化合物是一种
这是一种有价值和有保证的方法,但由于需要一次测试一种化合物,
时间它也没有探索组合的效果,它不能测试这些化合物在ALS中的作用。
发病率。考虑到老年人服用的药物种类繁多,
联合用药可能是相关的,我们建议,一个有价值的平行方法将是一个
流行病学筛查过程,以测试目前使用的任何药物是否与ALS发病率相关
或者生存这将类似于体外高通量筛选,但使用新的统计方法,
探索高维“大”流行病学数据(许多人,许多药物)与
ALS和ALS生存:具体来说,布尔逻辑回归和随机森林在一个嵌套的病例对照和
生存分析框架。这些方法允许有效地探索高维的,可能的
相关的,单个药物和不同药物组合之间的关联数据,
一个结果,这里是ALS。为了实现这一点,我们建议使用两个并行的非常大的数据集,
前瞻性和客观地收集药物和健康数据:丹麦注册系统和
以色列Clalit卫生系统,共有约4,300例ALS病例和超过30万例对照。通过
在不同人群中使用这两个数据集,我们将增加识别因果关系的概率。
通过鉴定在两个群体中筛选阳性的化合物。这项工作的结果有
确定目前使用的药物或这些药物的组合可能会影响ALS的可能性,
生存与ALS任何积极的结果都可能开辟新的研究途径,包括有针对性的临床试验
以及流行病学研究和实验室研究潜在的新方向,
机制等
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)
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Marc G Weisskopf其他文献
The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation
阿片样肽强啡肽介导海马苔藓纤维突触的异突触抑制并调节长时程增强
- DOI:
10.1038/362423a0 - 发表时间:
1993-04-01 - 期刊:
- 影响因子:48.500
- 作者:
Marc G Weisskopf;Robert A Zalutsky;Roger A Nicoll - 通讯作者:
Roger A Nicoll
Marc G Weisskopf的其他文献
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{{ truncateString('Marc G Weisskopf', 18)}}的其他基金
Child and adult Metal exposures, gene expression and neuropathologically confirmed Alzheimer's Disease
儿童和成人金属暴露、基因表达和神经病理学证实的阿尔茨海默病
- 批准号:
10901032 - 财政年份:2023
- 资助金额:
$ 23.29万 - 项目类别:
Military exposures and ALS in a large veteran population
大量退伍军人中的军事暴露和 ALS
- 批准号:
10701049 - 财政年份:2022
- 资助金额:
$ 23.29万 - 项目类别:
Military exposures and ALS in a large veteran population
大量退伍军人中的军事暴露和 ALS
- 批准号:
10609998 - 财政年份:2022
- 资助金额:
$ 23.29万 - 项目类别:
International Society for Environmental Epidemiology (ISEE) Annual Conference
国际环境流行病学学会(ISEE)年会
- 批准号:
10432038 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis
持久性有机污染物、免疫系统和肌萎缩侧索硬化症的病前生物标志物
- 批准号:
10438145 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
Metals and Developmental Origins of Late Life Cognitive Function
金属与晚年认知功能的发育起源
- 批准号:
10256790 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis
持久性有机污染物、免疫系统和肌萎缩侧索硬化症的病前生物标志物
- 批准号:
10119592 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
Metals and Developmental Origins of Late Life Cognitive Function
金属与晚年认知功能的发育起源
- 批准号:
10653000 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
International Society for Environmental Epidemiology (ISEE) Annual Conference
国际环境流行病学学会(ISEE)年会
- 批准号:
10207644 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
Metals and Developmental Origins of Late Life Cognitive Function
金属与晚年认知功能的发育起源
- 批准号:
10027714 - 财政年份:2020
- 资助金额:
$ 23.29万 - 项目类别:
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