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

基本信息

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
项目类别：
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

项目摘要

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 - 生物信息学核心该计划的总体科学目标是了解小儿艾滋病毒的免疫确定因子水库建立和维护。生物信息学核心的目的是提供骨干该计划的结构，用于全面的大规模多态数据集成，使颗粒状全系统分析以了解小儿艾滋病毒水库。尖端高维的冒险单细胞技术（依赖于低血或组织输入）正在迅速帮助开发工具可以提供有关儿童艾滋病毒的机械洞察力，并确定未来治疗的治疗靶标干预措施。生物信息学核心提案三个特定目标以支持该研究计划。在 AIM 1，核心将为项目提供生物统计学支持和样本/数据管理以及跟踪成员。核心将利用实验室库存管理系统（LIMS） - OPENSPECEMEN）埃默里大学信息技术基础设施。在AIM 2中，核心将处理和分析计划调查人员使用生物信息学管道生成的多素数据，实施最佳实践每个OMIC的工作流程。在AIM 3中，生物信息学核心将整合在项目1-3。然后，我们将有能力构建描述代谢和的主机响应网络模型免疫反应级联支持HIV/SIV水库的建立和/或维护。这些级联将用于构建模型，以预测可以在独立的测试数据集。这三个项目中的每个项目都将采用相似和协同作用生成有关小儿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中结合这些免疫，病毒学和分子数据集的专业知识并使用机器学习开发模型，使宿主免疫的额外见解确定病毒水库。总共生物信息学核心将提供一个平台，将指导标识和对理论干预措施的实验验证，可以帮助限制童年时期的艾滋病毒水库。