Research Support Core C: Computational Biology in Substance Use

研究支持核心 C：物质使用中的计算生物学

基本信息

批准号：
10632097
负责人：
MARK R CHANCE
金额：
$ 73.51万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10632097
关键词：
Address Area Automobile Driving Behavioral Bioinformatics Biological Biological Assay Biometry Biomimetics Blood - brain barrier anatomy Cannabis Cell model Cells Clinical Cocaine Color Comprehensive Cancer Center Computational Biology Constipation Data Data Analyses Data Set Data Storage and Retrieval Databases Dedications Defect Development Dimensions Disease Disease Progression Doctor of Medicine Doctor of Philosophy Drug usage Experimental Designs Faculty Fentanyl Flow Cytometry Functional disorder Funding Genes Genetic Transcription Genomics HIV Health Heroin Homeostasis Immune Immune system Immunologics Intestinal permeability Knowledge Maps Mass Spectrum Analysis Measures Meta-Analysis Metabolism Methamphetamine Methods Modeling Molecular Mucous Membrane Multiomic Data National Institute of Drug Abuse Neurocognitive Neurologic Neurological outcome Opioid Pathology Pathway interactions Patients Persons Pharmaceutical Preparations Physiological Plasma Post-Translational Protein Processing Postdoctoral Fellow Preparation Proteome Proteomics Protocols documentation Reporting Research Research Personnel Research Support Resolution Resource Sharing Resources Risk Sampling Services Severity of illness Small RNA Source Specimen Structure Substance Use Disorder Substance of Abuse System Technology Tissue Model Tissues Training Untranslated RNA Viral Virus Latency arm bacterial community biomarker identification biomarker validation body system cohort complex data computational pipelines computing resources cytokine data acquisition data curation data dissemination data integration data management design drug testing epigenome gastrointestinal gastrointestinal function graduate student gut dysbiosis in vivo longitudinal analysis member metabolome metabolomics microbial microbiome multiple omics new technology novel therapeutic intervention personalized approach professor programs public database response role model single-cell RNA sequencing stem substance use therapeutic development transcriptome sequencing transcriptomics

项目摘要

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.

项目摘要 - 物质使用核心 C 中的计算生物学已经进行了大量研究来确定吸毒对身体的影响控制免疫系统先天性和适应性臂完整性的机制， HIV 持续存在的胃肠道 (GI) 功能和神经认知疾病。研究导致了相互矛盾的结果，很大程度上是因为这些系统的复杂性和旨在测量不同臂、细胞和功能的测定分辨率低。能够准确评估物质使用的测定也是这些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。来解决这些问题，并支持 NIDA 资助的项目。在 CWRU 和全国范围内，CWRU 物质使用影响卓越中心 HIV 将依赖于物质使用研究支持核心 C 中的计算生物学。该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、代谢组学、蛋白质组学、生物信息学和计算为中心研究人员提供的生物学资源该共享资源利用了多种技术。在 Mark Chance、Adam Burgener、Saba Valadkhan 和 Konstantin 博士的指导下 Leskov 提供先进的计算和实验平台来服务物质使用计划和中心的核心 C 调查员将提供集中化的服务。为所有中心研究人员提供数据管理和分析资源，以便进行导航 “组学”景观无缝并推动各种“组学”的适当选择它将重点关注“组学”数据采集和特定实验设计的技术。存储（目标 1）、训练和数据分析（目标 2）以及数据集成、生物标志物验证、并对这些数据集进行建模（目标 3）。Core C 的交付成果将是一个迭代数据库。所有实验数据集，包括协议和样本标识符（目标 1），最先进的对来自所有“组学”平台的所有数据集以及可以提供的分析进行分析药物水平的定量评估（目标 2）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、肠道渗透性、血脑屏障受损以及免疫稳态和功能丧失。这种综合方法将确定艾滋病毒疾病进展的预测因素，具体针对单个和每个器官系统都使用每种药物，这可能会导致开发专为纠正胃肠道、神经和免疫病理学而定制的治疗方法吸毒者和艾滋病毒感染者。