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.

数学建模与生物信息学核心课题综述 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，他们在对艾滋病毒病毒动态进行建模方面经验丰富， 抗逆转录病毒治疗，艾滋病毒储存库的建立，以及潜伏期反转剂对 并在ART终止后病毒载量反弹的时间上。我们也有开发的经验 后处理控制模式。此外，我们在艾滋病毒序列分析和生物信息学方面也有经验 这将使我们能够从反弹的病毒中获得信息。我们的技术专长包括与 确定性和随机性模型以及模拟模型的开发。我们已经证明 能够根据数据拟合模型、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。团队成员注意 只有建模经验，但也曾与三个项目PI一起工作过，工作良好 两性关系。Core还拥有通过Los Alamos National提供的一流计算资源 实验室。将由Core开发的模型将解决儿科疾病治愈或病毒缓解的策略 成人艾滋病毒病例以及感染SIV的非人灵长类病例。这些模型将为以下方面提供基础 不同项目之间的协同作用，其中从一个领域的模型学到的信息可以为模型提供信息 在另一个区域。例如，免疫系统不成熟的儿科患者模型与 HIV感染成人的模型结果，可能提供关于更发达的免疫作用的信息 艾滋病控制中的应对措施。检查点抑制剂和潜伏期反转剂的作用模型 非人灵长类动物可能会告知免疫调节剂对感染艾滋病毒的儿童和成人的影响。因此， 通过建模，我们预计将从所有三个研究项目获得的信息整合在一起，从而使 实现病毒缓解或治愈的总体目标。