Research Support Core C: Computational Biology in Substance Use

项目摘要-物质使用计算生物学核心C 已经进行了大量的研究，以确定药物使用对 控制免疫系统的先天和适应性臂的完整性的机制， 胃肠道（GI）功能和神经认知疾病的背景下，艾滋病毒的持久性。等 研究导致了相互矛盾的结果，主要是因为这些系统的复杂性和 旨在测量不同臂、细胞和功能的测定的低分辨率。缺乏 可以提供对物质使用的准确评估的测定也是这些问题的来源。 试图将物质使用的下游机制联系起来的相互矛盾的结果。 艾滋病的严重程度。为了解决这些问题，并支持NIDA资助的项目， 在CWRU和全国范围内，CWRU卓越中心对物质使用的影响， 艾滋病毒将依赖于物质使用研究支持核心C中的计算生物学。 这个核心是一个全面的共享资源，提供先进的转录组学， 基因组学、功能微生物组学、代谢组学、蛋白质组学、生物信息学和计算 生物资源中心研究人员。此共享资源利用多种技术 在Mark Chance、Adam Burgener、Saba Valadkhan和Konstantin博士的指导下， 提供先进的计算和实验平台， 物质使用项目和中心的调查员核心C将提供一个集中的 数据管理和分析资源，以所有中心的研究人员进行导航， “组学”景观无缝，并推动广泛的“组学”的适当选择 具体实验设计的技术。它将专注于“组学”数据采集， 存储（目标1），训练和数据分析（目标2），以及数据整合，生物标志物验证， 并对这些数据集进行建模（目标3）。核心C的可交付成果将是一个迭代数据库 所有实验数据集，包括方案和样本标识符（目标1），最新技术水平 分析来自所有“组学”平台的所有数据集以及可以提供 药物水平的定量评估（目标2）。目标3将侧重于整合和执行 对所有队列和生理系统的所有数据集进行荟萃分析，以定义 可卡因，甲基苯丙胺， 阿片类药物和大麻对艾滋病毒潜伏期，神经认知功能障碍，便秘，肠 渗透性、血脑屏障损伤以及免疫稳态和功能丧失。 这种综合方法将确定HIV疾病进展的预测因子， 每个器官系统的每种药物的多用户，这可能导致发展 为纠正胃肠道、神经和免疫病理而量身定制的治疗方法 在吸毒和艾滋病毒感染者中。

Project Summary - Computational Biology in Substance Use Core C A large number of studies have been performed to identify the impact of drug use on the mechanisms that govern the integrity of the innate and adaptive arms of the immune system, gastrointestinal (GI) function, and neurocognitive disease in the context of HIV persistence. Such studies have led to conflicting results largely because of the complexity of these systems and the low resolution of assays aimed at measuring the different arms, cells, and functions. The lack of assays that can provide an accurate assessment of substance use is also at the source of these conflicting results that have attempted to associate mechanisms downstream of substance use. on HIV disease severity. To address these issues, and in support of the NIDA funded projects at CWRU and nationwide, the CWRU Center for Excellence on the Impact of Substance Use on HIV will rely on the Computational Biology in Substance Use Research Support Core C. This core is a comprehensive shared resource that provides advanced transcriptomics, genomics, functional microbiome, metabolomics, proteomics, bioinformatics, and computational biology resources to Center investigators. This shared resource leverages multiple technologies under the direction of Drs. Mark Chance, Adam Burgener, Saba Valadkhan, and Konstantin Leskov that provide that provide advanced computational and experimental platforms to serve the Substance Use program and the Center’s investigators. Core C will provide a centralized data management and analysis resource to all Center investigators making the navigation of the ‘omics’ landscape seamless and driving appropriate choices of a wide array of ‘omics’ technologies for specific experimental designs. It will be focused on ‘omics’ data acquisition and storage (Aim 1), training and data analysis (Aim 2), and data integration, biomarker validation, and modeling of these datasets (Aim 3). The deliverables of Core C will be an iterative database of all experimental datasets, including protocols and sample identifiers (Aim 1), state of the art analysis of all datasets stemming from all ‘omics’ platforms as well as assays that can provide quantitative assessment of drug levels (Aim 2). Aim 3 will focus on integrating and performing meta-analysis of all datasets across all cohorts and physiological systems to define generalizable and distinct mechanisms that underlie the impact of cocaine, methamphetamine, opioids, and cannabis on HIV latency, neurocognitive dysfunction, constipation, intestinal permeability, damage to the blood brain barrier, and loss of immune homeostasis and function. This integrated approach will identify predictors of HIV disease progression specific to single and poly-users of each drug for each organ system, which could lead to the development of therapeutic approaches tailored to correct the GI, neurological, and immunological pathologies in persons with drug use and HIV.