Project 3 - Quantitative analysis and computational modeling of viral rebound
项目3——病毒反弹的定量分析和计算模型
基本信息
- 批准号:9322143
- 负责人:
- 金额:$ 18.1万
- 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:2017-06-23 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsBiological MarkersBiostatistical MethodsCell TherapyCellsCerebrospinal FluidComputer SimulationComputing MethodologiesDataData AnalysesData SetData SourcesDatabasesDevelopmentDimensionsDiseaseEthicsExperimental DesignsFarGoGene ExpressionGene ProteinsGoalsHIVHIV-1HumanImmuneImmunologicsInfectionInterruptionMacacaMeasurementMethodsModelingMolecularNaturePatientsPhasePlasmaPopulationPrognostic MarkerProteinsRoleSIVSamplingServicesSystemTherapeuticTherapeutic InterventionTimeTranslatingViralViral Load resultViral MarkersViral reservoirWorkanimal dataantiretroviral therapybasechemokineclinically relevantcytokinedata integrationdata modelingdensityexperimental studyhigh dimensionalityinsightmathematical modelmultimodalityprogramsresponsesample collectiontargeted treatmenttherapeutic evaluationviral rebound
项目摘要
PROJECT 3 -ABSTRACT
We propose to use advanced computational methods to understand the causes & dynamics of SIV rebound in
macaques. This project is a part of an overall program that combines extensive experimental work in SIV-infected
macaques with quantitative analysis and computational models to provide a common framework to understand
viral rebound following the cessation of antiretroviral therapy (ART) in suppressed macaques. The connections
to HIV are clear, and will be enhanced by the parallel development and comparison of experimental-data-based
computational models of SIV in macaques and HIV in humans. Clinical relevance is further enhanced by the use
of the developed models to simulate many different therapeutic approaches to find methods to delay or eliminate
viral rebound. As part of the overall Program, Project 3 (“Quantitative analysis and computational modeling of
viral rebound”) will perform quantitative data analysis of all experimental data from the projects and cores of the
Program, identify biomarkers across multiple data sources that are predictive of viral rebound, and develop and
validate a predictive computational model with parameters specific to macaques and SIV. Projects 1 and 2 and
the BSL3 core will conduct experiments with quantitative readouts of many different types including: gene
expression, chemokine/cytokine expression, immune cell metrics, viral reservoir characterization, and the viral
load in both the plasma and CSF. These measurements will be made at multiple time points, including during
active infection, suppression by ART, release from suppression by cessation of ART, and post-cessation viral
rebound. The careful and thorough analysis of data proposed in this project will not just provide a service to the
other projects, but also enable synthesis and integration of data across all the projects. This will aid the Program
in developing a rigorous, system-level understanding of viral rebound. In order to accomplish this, we have
identified five goals for Project 3: (a) to provide quantitative analysis of the multimodal, diverse data within each
project and across projects; (b) to build a mechanistic computational model that integrates this data; (c) to assist
in experimental design, selecting appropriate experimental conditions by analyzing previous data; (d) to identify
biomarkers of viral rebound; and (e) to translate this SIV-in-macaque study and its insights to HIV in humans by
comparing our mechanistic computational models of SIV to our models of HIV. These goals have been
incorporated and distilled into three aims for Project 3: (1) Understand the dynamics of viral rebound using
longitudinal data. (2) Identify pre- and early post-cessation biomarkers of viral rebound. (3) Predict rebound-
targeting therapeutic interventions in SIV and HIV.
项目3 -摘要
我们建议使用先进的计算方法来理解SIV反弹的原因和动力学,
猕猴该项目是一个整体计划的一部分,该计划结合了SIV感染者的广泛实验工作,
猕猴与定量分析和计算模型,以提供一个共同的框架,以了解
在受抑制的猕猴中停止抗逆转录病毒治疗(ART)后病毒反弹。的连接
艾滋病毒是明确的,并将通过平行发展和比较实验数据的基础上加强
猕猴SIV和人类HIV的计算模型。临床相关性通过使用
开发的模型来模拟许多不同的治疗方法,以找到延迟或消除
病毒反弹作为整个计划的一部分,项目3(“定量分析和计算建模,
病毒反弹”)将对来自项目和核心的所有实验数据进行定量数据分析,
编程,在多个数据源中识别可预测病毒反弹的生物标志物,并开发和
验证具有猕猴和SIV特定参数的预测计算模型。项目1和2以及
BSL 3核心将进行许多不同类型的定量读出实验,包括:基因
表达、趋化因子/细胞因子表达、免疫细胞指标、病毒储库表征和病毒表达。
在血浆和脑脊液中的含量。这些测量将在多个时间点进行,包括在
活动性感染、ART抑制、ART停止后抑制解除和停止后病毒感染
反弹对本项目中提出的数据进行仔细和彻底的分析不仅可以为
此外,还可以对所有项目的数据进行综合和整合。这将有助于该计划
对病毒反弹形成严格的系统级理解。为了实现这一目标,我们必须
确定了项目3的五个目标:(a)对每个项目中的多模式、多样化数据进行定量分析
项目和跨项目;(B)建立一个整合这些数据的机械计算模型;(c)协助
在实验设计中,通过分析以往的数据,选择合适的实验条件;(d)识别
病毒反弹的生物标志物;以及(e)通过以下方式将猕猴中的SIV研究及其见解转化为人类中的HIV
将SIV的机械计算模型与HIV的模型进行比较。这些目标一直是
整合并提炼为项目3的三个目标:(1)了解病毒反弹的动态,
纵向数据(2)确定病毒反弹的前和早期停止后生物标志物。(3)预测反弹-
针对SIV和HIV的治疗干预。
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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Feilim C Mac Gabhann其他文献
Feilim C Mac Gabhann的其他文献
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{{ truncateString('Feilim C Mac Gabhann', 18)}}的其他基金
Pre-Doctoral Training Program in Computational Medicine
计算医学博士前培训项目
- 批准号:
10190960 - 财政年份:2017
- 资助金额:
$ 18.1万 - 项目类别:
Endothelial cell decisions integrate soluble and matrix-bound VEGF gradients
内皮细胞决策整合了可溶性和基质结合的 VEGF 梯度
- 批准号:
7862651 - 财政年份:2009
- 资助金额:
$ 18.1万 - 项目类别:
Endothelial cell decisions integrate soluble and matrix-bound VEGF gradients
内皮细胞决策整合了可溶性和基质结合的 VEGF 梯度
- 批准号:
7928769 - 财政年份:2009
- 资助金额:
$ 18.1万 - 项目类别:
Endothelial cell decisions integrate soluble and matrix-bound VEGF gradients
内皮细胞决策整合了可溶性和基质结合的 VEGF 梯度
- 批准号:
8127746 - 财政年份:2009
- 资助金额:
$ 18.1万 - 项目类别:
Endothelial cell decisions integrate soluble and matrix-bound VEGF gradients
内皮细胞决策整合了可溶性和基质结合的 VEGF 梯度
- 批准号:
7511209 - 财政年份:2008
- 资助金额:
$ 18.1万 - 项目类别:
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