High-Definition Characterization of the Persistence and Perturbation of the HIV Reservoir: Data Analytics & Modeling Core

HIV 病毒库的持续性和扰动的高清表征：数据分析

• 批准号: 10469110
• 负责人: Jonathan Li
• 金额: $ 9.91万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469110
• 关键词: Antibody Therapy; Bioinformatics; Biological; Biometry; Cells; Collaborations; Complex; Consequences of HIV; Data; Data Analytics; Data Set; Disease remission; Doctor of Philosophy; Equilibrium; Genome; Goals; HIV; HIV Infections; Immune response; Immunologics; Immunotherapeutic agent; Individual; Infection; Investigation; Maintenance; Methodology; Methods; Modeling; Nature; Neuraxis; Phenotype; Phylogenetic Analysis; Plasma; Property; Proviruses; Research; Research Personnel; Research Project Grants; Role; Source; Technical Expertise; Therapeutic; Time; Tissues; Viral; Viremia; advanced analytics; analytical method; antiretroviral therapy; biomathematics; data modeling; design; experience; experimental study; high dimensionality; integration site; mathematical model; member; multiple omics; next generation; novel therapeutics; outcome prediction; peripheral blood; programs; single cell sequencing; viral rebound

PROJECT SUMMARY HIV infection can persist long-term antiretroviral therapy as a reservoir of provirus integrated into host cell genomes. The stability and activity of this reservoir depends on the complex interplay between viral and host mechanisms. The overall goal of this P01 is to characterize the mechanisms of formation, persistence, reactivation, and therapeutic responsiveness of the HIV reservoir in unprecedented detail. This will involve generating high-dimensional and longitudinal single-cell and single-genome datasets. The role of the Data Analytics & Modeling Core is to provide specialized quantitative methods to each of the research projects to aid in the design and interpretation of the experimental studies. The Core will bring together analytical experts contributing to each project to collaboratively plan, conduct, and interpret analyses. Core members will develop and apply state-of-the-art bioinformatic methods to interpret high-dimensional biological data characterizing the HIV reservoir. They will additionally develop and apply mechanistic viral dynamics models to understand the mechanism of reservoir formation, persistence, and reactivation, with the long-term goal of predicting outcomes of novel therapeutics. Overall the Data Analytics & Modeling Core will advance the goals of this program project by building a more complete understanding of the causes and consequences of HIV reservoir dynamics.

项目总结 HIV感染可以持续长期的抗逆转录病毒治疗，因为它是整合到宿主细胞中的前病毒的储存库 基因组。这个储存库的稳定性和活性取决于病毒和宿主之间复杂的相互作用 机制。这个P01的总体目标是表征形成、持续、 艾滋病毒储存库的重新激活和治疗反应的前所未有的细节。这将涉及到 生成高维和纵向的单细胞和单基因组数据集。数据的作用 分析与建模的核心是为每个研究项目提供专门的量化方法 协助设计和解释实验研究。核心将汇集分析专家 协助每个项目协作计划、执行和解释分析。核心成员将得到发展 并应用最先进的生物信息学方法来解释表征 艾滋病毒蓄水池。他们还将开发和应用机械病毒动力学模型来理解 储集层形成、持续和重新激活的机制，长期目标是预测 新疗法的结果。总体而言，数据分析和建模核心将推进这一目标 通过建立对艾滋病毒携带者的原因和后果的更全面的了解来实施计划项目 动力学。