Core 4: Statistics and Mathematical Modeling Core

核心4：统计和数学建模核心

• 批准号: 10374247
• 负责人: Cliburn C Chan
• 金额: $ 14.3万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-24 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374247
• 关键词: Core; Statistics; Mathematical; Modeling

ABSTRACT – Statistics and Mathematical Modeling Core (Core 4) The Statistics and Mathematical Modeling Core (Core 4) will provide data management, statistical analysis and mathematical modeling support for the Program’s overall goal to understand the immunological and viral determinants of congenital CMV infection. The Core has worked with both projects to define a comprehensive sample size analysis for all experiments and will also analyze the data generated from those experiments to identify correlates of placental transmission and viral load using descriptive statistics and statistical visualization as well as univariate and multivariate regression modelling. Special attention is paid to the use of use of methods that optimize information extraction from small sample sizes in both the experimental design and subsequent analysis. An innovative aspect of the Core is the proposed development of mathematical models and computer simulations to explore how different mechanistic assumptions affect viral population growth and the likelihood of placental transmission under different immune control scenarios. These mathematical models will take advantage of and integrate the viral population genetics analyses (Core 3), host (Core 1) and CMV (Core 2) longitudinal measurements, and systematic experimental perturbations in naïve and non-naïve hosts (Projects 1 and 2) to evaluate and generate hypotheses about how host-CMV interactions modulate the risk of viral dissemination and placental transmission. The pharmacokinetics effort within the Core will develop a semi-physiologic based PK model to characterize the maternal, fetal, and maternal-fetal distribution of HIG after administration to RhCMV-infected rhesus dams or directly to RhCMV- infected fetuses to generate optimal dosing regimens of HIG for materno-fetal prevention and treatment of congenital CMV. Core 4 will also work with the Admin Core to define the schema to capture critical data summaries in a REDCap database, create templates to track versioning and experimental metadata in the Duke Box service used for data sharing across projects and cores. Finally, Core 4 will work with the Admin Core and in consultation with the Duke Office of Advancing Scientific Integrity, Services, and Training (ASIST) to establish Program-specific data management SOPs and Scientific Culture and Accountability Plan (SCAP) for the Program. Core 4 supports all components in this Program (Project 1, 2; Core 1, 2, 3; Admin Core), and provides a centralized resource for exploratory data analysis, statistical analysis, pharmacokinetics studies, mathematical modeling, and data management. Core 4 will be central to the preparation of all Program presentations, reports, and manuscripts that seek to establish the immunologic and virologic factors involved in placental transmission of CMV as a strategy to guide future vaccine design and evaluation

摘要--统计和数学建模核心(核心4) 统计和数学建模核心(核心4)将提供数据管理、统计分析 和数学建模支持该计划的总体目标，以了解免疫学和病毒 先天性巨细胞病毒感染的决定因素。核心已经与这两个项目合作，定义了一个全面的 所有实验的样本量分析，还将分析这些实验产生的数据，以 使用描述性统计和统计学方法确定胎盘传播和病毒载量的相关性 可视化以及单变量和多变量回归建模。特别注意使用 在两个实验设计中使用从小样本中优化信息提取的方法 以及随后的分析。核心的一个创新方面是数学的拟议发展 探索不同机制假设如何影响病毒种群的模型和计算机模拟 在不同的免疫控制方案下的生长和胎盘传播的可能性。这些 数学模型将利用和整合病毒种群遗传学分析(核心3)，宿主 (CORE 1)和CMV(CORE 2)纵向测量，以及在幼稚状态下的系统实验扰动 和非幼稚的宿主(项目1和2)，以评估和生成关于宿主-CMV如何 相互作用调节病毒传播和胎盘传播的风险。药代动力学研究进展 在核心内将开发一个基于半生理学的PK模型，以表征母亲、胎儿和 重组人巨细胞病毒感染恒河猴和直接接种人免疫球蛋白的母婴分布 感染胎儿产生最佳剂量的HIG预防和治疗母婴 先天性巨细胞病毒。核心4还将与管理核心一起定义捕获关键数据的架构 RedCap数据库中的摘要，创建模板以跟踪版本控制和 用于跨项目和核心共享数据的Duke Box服务。最后，核心4将与管理员一起工作 核心，并与杜克大学促进科学诚信、服务和培训办公室(ASIST)协商 建立特定于项目的数据管理SOP和科学文化与责任计划(SCAP) 对于该计划。核心4支持本计划中的所有组件(项目1、2；核心1、2、3；管理核心)、 并为探索性数据分析、统计分析、药代动力学 学习、数学建模和数据管理。核心4将是所有计划编制工作的核心 寻求确定免疫学和病毒学因素的演示文稿、报告和手稿 将CMV胎盘传播作为指导未来疫苗设计和评价的一种策略