Core-004

摘要-统计与数学建模核心（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，以了解免疫和病毒 先天性CMV感染的决定因素。核心与这两个项目合作， 所有实验的样本量分析，还将分析这些实验产生的数据， 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 在实验设计中使用优化小样本量信息提取的方法 随后的分析。核心的一个创新方面是建议发展数学 模型和计算机模拟，以探索不同的机制假设如何影响病毒种群 生长和胎盘传播的可能性在不同的免疫控制情况下。这些 数学模型将利用并整合病毒群体遗传学分析（核心3），宿主 (Core 1）和CMV（核心2）纵向测量，和系统的实验扰动，在幼稚 和非幼稚宿主（项目1和2），以评估和产生关于宿主-CMV 相互作用调节病毒传播和胎盘传播的风险。药代动力学的努力 在核心内，将开发基于半生理的PK模型，以表征母体、胎儿和 RhCMV感染恒河猴母鼠或直接给药RhCMV后HIG的母胎分布感染的胎儿产生最佳剂量方案的HIG的母胎预防和治疗 先天性CMV Core 4还将与Admin Core一起定义捕获关键数据的模式 REDCap数据库中的摘要，创建模板以跟踪 杜克Box服务用于跨项目和核心共享数据。最后，Core 4将与Admin 核心并与杜克推进科学诚信、服务和培训办公室（ASIST）协商 制定项目特定的数据管理SOP和科学文化与责任计划（SCAP） 为了这个项目。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 研究、数学建模和数据管理。核心4将是所有计划编制的核心 介绍，报告和手稿，寻求建立免疫和病毒学因素参与 CMV的胎盘传播作为指导未来疫苗设计和评价的策略

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 RhCMVinfected 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