Immune determinants of pediatric HIV/SIV reservoir establishment and maintenance

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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.