Immune determinants of pediatric HIV/SIV reservoir establishment and maintenance

儿科 HIV/SIV 病毒库建立和维持的免疫决定因素

• 批准号: 10701469
• 负责人: Ashish Arunkumar Sharma
• 金额: $ 6.94万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701469
• 关键词: Adolescence; Animals; Big Data; Binding; Bioinformatics; Biological Assay; Biological Models; Biometry; Blood; Cells; Child; Childhood; Clinical; Data; Data Analyses; Data Set; Disease; Ensure; Environment; Equipment and supply inventories; Flow Cytometry; Future; Goals; HIV; Human; Human Resources; Immune; Immune response; Immunologics; Individual; Information Technology; Infrastructure; Interruption; Life; Machine Learning; Maintenance; Meta-Analysis; Metabolic; Metadata; Methodology; Modeling; Molecular; Multiomic Data; Network-based; Outcome; Participant; Pathway interactions; Plasma; Positioning Attribute; Pre-Clinical Model; Process; Protocols documentation; Proviruses; Quality Control; Reporting; Research; Research Personnel; Research Support; SIV; Sampling; Secure; Specimen; Standardization; Structure; System; Testing; Therapeutic Intervention; Tissues; Universities; Validation; Vertebral column; Viral Load result; Viral reservoir; Virus; bioinformatics pipeline; cohort; curative treatments; cytokine; data integration; data management; data tools; epigenome; experimental study; high dimensionality; insight; integration site; member; metabolomics; model building; multidimensional data; multiple omics; network models; nonhuman primate; novel therapeutics; pediatric human immunodeficiency virus; predicting response; predictive modeling; programs; single cell sequencing; single cell technology; therapeutic target; tool development; transcriptome; viral rebound; virus host interaction

ABSTRACT – Bioinformatics Core This proposed Program’s overarching scientific goal is to understand the immune determinants of pediatric HIV reservoir establishment and maintenance. The objective of the Bioinformatics Core is to provide the backbone structure for this Program for comprehensive large scale multiomic data integration, enabling granular yet systems-wide analyses to understand pediatric HIV reservoirs. The advent of cutting-edge high-dimensional single cell technologies - that rely on low blood or tissue input - is quickly aiding the development of tools that can provide mechanistic insight into HIV in children and identify therapeutic targets for future curative interventions. The Bioinformatics Core proposes three Specific Aims in support of this research Program. In Aim 1, the Core will provide biostatistical support and sample/data management and tracking to the Project members. The Core will leverage the Lab Inventory Management System (LIMS) – OpenSpecimen) offered via the Emory University information technology infrastructure. In Aim 2, the Core will process and analyze multiomic data generated by Program investigators using bioinformatics pipelines implementing best-practice workflow for each omic. In Aim 3, the Bioinformatics Core will integrate multiomic datasets generated in Projects 1-3. We will then be in a position to build host response network models that depict the metabolic and immune response cascades that support the establishment and/or maintenance of HIV/SIV reservoirs. These cascades will be used to build models that predict ways to perturb HIV persistence that can be confirmed in independent test datasets. Each of the three Projects, while unique in focus, will employ similar and synergistic methodology to generate big data on the pediatric immune environment. The Bioinformatics Core provides expertise to combine these immunological, virological, and molecular datasets in meta-analyses and use machine learning to develop models that give expansive insight into host immune determinants of viral reservoirs. Altogether the Bioinformatics Core will provide a platform that will guide the identification and experimental validation of therapeutic interventions that can help limit HIV reservoirs during childhood.

摘要--生物信息学核心 这一计划的主要科学目标是了解儿童艾滋病毒的免疫决定因素 水库的建立和维护。生物信息学核心的目标是提供骨干 本计划的结构用于全面的大规模多组数据集成，实现细粒度的 全系统分析，以了解儿科艾滋病毒携带者。尖端高维技术的到来 单细胞技术--依赖于低血或组织输入--正在迅速帮助开发能够 可以提供对儿童艾滋病毒的机械性洞察，并为未来的治疗确定治疗目标 干预措施。生物信息学核心提出了支持这一研究计划的三个具体目标。在……里面 目标1，核心将为项目提供生物统计支持以及样本/数据管理和跟踪 会员。核心将利用通过以下方式提供的实验室库存管理系统(LIMS)-Openspecimen 埃默里大学的信息技术基础设施。在目标2中，核心将处理和分析 项目调查人员使用实施最佳实践的生物信息学管道生成的多组数据 每个OMIC的工作流程。在目标3中，生物信息学核心将整合在 项目1-3。然后，我们将能够构建主机响应网络模型，描述新陈代谢和 支持建立和/或维持艾滋病毒/SIV储存库的免疫反应级联反应。这些 级联将被用来建立预测扰乱艾滋病毒持久性的方法的模型，这些方法可以在 独立的测试数据集。这三个项目虽然各有侧重，但都将采用相似和协同的方式 生成有关儿科免疫环境的大数据的方法。生物信息学核心提供 在荟萃分析和使用中结合这些免疫学、病毒学和分子数据集的专业知识 机器学习开发模型，对病毒的宿主免疫决定因素提供广泛的洞察 水库。总之，生物信息学核心将提供一个平台，指导识别和 可帮助限制儿童时期艾滋病毒宿主的治疗干预措施的实验验证。