Core B: Computational

核心 B：计算

• 批准号: 10246900
• 负责人: ALAN S PERELSON
• 金额: $ 52.74万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-11 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246900
• 关键词: Address; Adult; Adverse drug effect; Aftercare; Age; Area; Bioinformatics; Biometry; Child; Childhood; Collaborations; Data; Data Analyses; Data Set; Development; Disease remission; Drug Kinetics; Early treatment; Experimental Designs; Fostering; Generations; Goals; HIV; HIV Infections; HIV-1; Human; Immune checkpoint inhibitor; Immune response; Immune system; Immunologic Markers; Immunomodulators; Immunotherapy; Individual; Infection Control; Kinetics; Laboratories; Length; Measures; Mission; Modeling; Outcome; Persons; Pharmacodynamics; Probability; Public Health; Research Project Grants; Research Support; Role; SIV; Sequence Analysis; Technical Expertise; Testing; Time; Viral; Viral Load result; Work; antiretroviral therapy; computing resources; experience; infant infection; inflammatory marker; inhibitor/antagonist; innovation; latent HIV reservoir; mathematical model; member; models and simulation; nonhuman primate; pediatric patients; pharmacometrics; predictive modeling; synergism; viral rebound

Project Summary for Mathematical Modeling and Bioinformatics Core The goal of this Core is to provide mathematical modeling and bioinformatics support for the three research projects. We have assembled a team of experts with experience in modeling HIV viral dynamics, the effects of antiretroviral therapy, the establishment of the HIV reservoir, and the effects of latency reversing agents on the reservoir and on the time to viral load rebound after ART termination. We also have experience in developing models of post-treatment control. In addition, we have experience in HIV sequence analysis and bioinformatics that will allow us to gain information from rebounding virus. Our technical expertise includes working with deterministic and stochastic models as well as in the development of simulation models. We have proven capabilities in fitting models to data, estimating parameters, parameter sensitivity analysis, parameter identification, pharmacokinetics, pharmacodynamics, pharmacometrics and biostatistics. Team members not only have modeling experience but have also worked with the three project PIs in the past and have good working relationships. The Core also has superb computing resources available through Los Alamos National Laboratory. The models to be developed by the Core will address strategies for cure or viral remission in pediatric and adult cases of HIV as well as in nonhuman primates infected with SIV. The models will provide a basis for synergy between the various projects, where information learned from models in one arena can inform models in another area. For example, models of pediatric patients with immature immune systems, when compared with model results for HIV-infected adults, may provide information about the role of more developed immune responses in HIV control. Models of the effects of checkpoint inhibitors and latency reversing agents in nonhuman primates may inform on the effects of immune modulators in HIV infected children and adults. Thus, through modeling we foresee integrating information obtained from all three research projects to benefit the overall goal of achieving viral remission or cure.

数学建模和生物信息学核心项目摘要 该核心的目标是为这三项研究提供数学建模和生物信息学支持 项目我们已经组建了一个专家团队，他们在模拟HIV病毒动力学、 抗逆转录病毒治疗，建立艾滋病毒库，以及潜伏逆转剂对艾滋病毒感染的影响。 库和ART终止后病毒载量反弹的时间。我们也有开发 治疗后控制模式。此外，我们在艾滋病毒序列分析和生物信息学方面拥有经验 让我们能从反弹的病毒中获取信息我们的技术专长包括： 确定性和随机模型以及模拟模型的开发。我们已经证明 能够将模型拟合到数据，估计参数，参数敏感性分析，参数 鉴定、药代动力学、药效学、药物计量学和生物统计学。团队成员不 我只有建模经验，但过去也曾与三个项目PI合作，并有良好的工作经验。 关系。核心还拥有一流的计算资源，可通过洛斯阿拉莫斯国家 实验室由核心开发的模型将解决儿科患者治愈或病毒缓解的策略 和成人HIV病例以及感染SIV的非人灵长类动物。这些模型将为 不同项目之间的协同作用，从一个竞技场的模型中获得的信息可以为模型提供信息 在另一个领域。例如，免疫系统不成熟的儿科患者的模型，当与 HIV感染成年人的模型结果，可能提供有关更发达的免疫系统的作用的信息。 艾滋病毒控制对策。检查点抑制剂和潜伏期逆转剂在 非人灵长类动物可能提供关于免疫调节剂在感染HIV的儿童和成人中的作用的信息。因此，在本发明中， 通过建模，我们可以预见，整合从所有三个研究项目中获得的信息， 达到病毒缓解或治愈的总体目标。