Patient Sampling and Genomics Core

患者采样和基因组学核心

• 批准号: 10170862
• 负责人: STEVEN M DUDEK
• 金额: $ 37.09万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10170862
• 关键词: Acute; Acute Lung Injury; Adult Respiratory Distress Syndrome; African American; Bioinformatics; Biometry; Blood; Blood specimen; Bronchoalveolar Lavage; Clinical; Clinical Data; Code; Critical Illness; Data; Development; Diagnostic; Disease Outcome; Doctor of Philosophy; Enrollment; Etiology; Excision; Genomics; Hispanics; Human; Human Resources; Immune Tolerance; Individual; Inflammatory; Informatics; Institutional Review Boards; Latino; Lung; Lymphocyte; Mechanical ventilation; Mediating; Medicine; Methodology; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Pharmacology; Phase; Phenotype; Pneumonia; Population; Process; Protocols documentation; Pulmonology; Reporting; Research; Research Personnel; Resolution; Resources; Role; Safety; Sampling; Sepsis; Severities; Severity of illness; Specialist; Specimen; Structure; Underrepresented Populations; Universities; Work; biobank; clinical database; clinical phenotype; improved; innovation; lung injury; macrophage; novel strategies; patient population; patient subsets; professor; programs; repaired; repository; respiratory; sample collection; single-cell RNA sequencing; transcriptome sequencing; transcriptomics; treatment response

PROJECT SUMMARY / ABSTRACT A critical translational component of this Program Project involves the correlative analysis of macrophages (Mφ) isolated from critically ill patients suffering from sepsis, pneumonia, and other acute insults that result in the devastating clinical syndrome of Acute Respiratory Distress Syndrome (ARDS). The Patient Sampling and Genomics Core (Core D) will perform the central function of collecting these Mφ samples and establishing and maintaining a clinical database of disease severity. Feasibility for obtaining sufficient samples for the proposed studies will be greatly enhanced through extensive utilization of a non-bronchoscopic BAL (NBBAL) approach, which results in diagnostic yields similar to bronchoscopic BAL and has an excellent safety profile in critically ill patients requiring mechanical ventilation. In addition, blood will be collected for isolation of peripheral blood mononuclear cells (PBMCs) for comparison with lung samples. Longitudinal samples will be collected from a subset of patients. Additionally, Core D will provide biostatistical analysis on these clinical samples as well as bioinformatic analysis on samples from all Projects, including bulk RNA-seq analysis, and single-cell RNA-seq (scRNA-seq) processing and analysis, as described in the individual Projects. A spectrum of clinical severity will be obtained to correlate disease outcomes with flow cytometric, transcriptomic, and functional analyses of Mφs, focusing on pathways relevant to each of the four Projects. Innovative aspects of this Core include the following: a) development of an unique biorepository of lung Mφ samples from patients with ARDS, including longitudinal samples from a subset of patients to characterize changes in lung Mφ populations during the phases of ARDS; b) scRNA-seq analysis of patient lung Mφ, representing a substantial methodological advance in Mφ analysis compared to other recent studies; c) extensive utilization of the NBBAL approach to greatly enhance sample collection since it can be performed safely and with high yield by respiratory therapists and fellow trainees; d) an integrated Core structure that combines patient sample acquisition with biostatistical and bioinformatic expertise and resources to maximize efficient utilization of these clinical data; e) sample collection from a diverse ICU patient population of under-represented and insufficiently studied groups (30-40% African-American and 30-40% Hispanic/Latino patients). f) Comparison of expression profiles in lung Mφ populations from ARDS patients with circulating PBMCs after removal of lymphocytes, which will improve the reported poor correlation between these sample types; g) inclusion of immune paralysis as phenotypic characterization of patient samples, which has not been evaluated in past studies of ARDS AMφ clinical samples; h) enhanced focus on sepsis and pneumonia-induced ARDS as the primary etiologies characterized by intensive lung Mφ analysis.

项目摘要 /摘要 该计划项目的关键翻译组成部分涉及巨噬细胞的相关分析（Mφ） 从患有败血症，肺炎和其他急性损伤的重症患者中分离出来 急性呼吸窘迫综合征（ARDS）的毁灭性临床综合征。患者采样和 基因组学核心（核心D）将执行收集这些Mφ样品并建立和 维持疾病严重程度的临床数据库。为提出的足够样品获得足够的样品的可行性 通过广泛利用非支气管镜BAL（NBBAL）方法，将大大增强研究， 这导致诊断产量类似于支气管镜BAL，并且在重病中具有出色的安全性。 需要机械通气的患者。另外，将收集血液以隔离外周血 单核细胞（PBMC）与肺样品进行比较。将从A收集纵向样品 患者子集。此外，核心D将对这些临床样本以及 对来自所有项目的样品的生物信息学分析，包括散装RNA-seq分析和单细胞RNA-Seq （SCRNA-SEQ）处理和分析，如各个项目中所述。一系列临床严重程度将 可以获得与流式细胞仪，转录组和功能分析相关的疾病结果， 专注于与四个项目中的每个项目相关的途径。 该核心的创新方面包括以下内容：a）开发肺部独特的生物库 来自ARDS患者的Mφ样品，包括来自一部分患者的纵向样本以表征 在ARDS期间，肺Mφ种群的变化； b）患者肺Mφ的scrna-seq分析， 与最近的其他研究相比，在Mφ分析中代表了大量方法论； c）广泛 使用NBBAL方法来增强样本收集，因为它可以安全地执行，并且 呼吸治疗师和学员的产量很高； d）结合患者的综合核心结构 具有生物统计和生物信息学专业知识和资源的样本采集，以最大程度地利用 这些临床数据； e）从代表性不足和人群中收集的样本ICU患者人群 研究组不足（30-40％的非裔美国人和30-40％的西班牙裔/拉丁裔患者）。 f）比较 去除后，来自循环PBMC的ARDS患者的肺Mφ种群的表达谱 淋巴细胞将改善这些样本类型之间报告的不良相关性； g）包含 免疫麻痹作为患者样品的表型表征，过去尚未评估 ARDSAMφ临床样品的研究； h）增强了对败血症和肺炎引起的ARD的关注 以密集肺Mφ分析为特征的主要病因。