Patient Sampling and Genomics Core

患者采样和基因组学核心

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要该计划项目的一个关键转化部分涉及巨噬细胞 (Mφ) 的相关分析从患有败血症、肺炎和其他急性损伤的危重患者中分离出来，这些患者会导致急性呼吸窘迫综合征 (ARDS) 的破坏性临床综合征。 Genomics Core（Core D）将执行收集这些 Mφ 样本并建立和维护疾病严重程度的临床数据库，以获取足够的样本。通过广泛使用非支气管镜 BAL (NBBAL) 方法将大大加强研究，其诊断结果与支气管镜 BAL 相似，并且在重症患者中具有出色的安全性此外，还会采集需要机械通气的患者的血液以分离外周血。将从肺样本中收集单核细胞（PBMC）以与肺样本进行比较。此外，Core D 还将提供这些临床样本的生物统计分析。对所有项目的样本进行生物信息分析，包括批量 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，将描述一系列临床严重程度。获得将疾病结果与 Mφs 的流式细胞术、转录组学和功能分析相关联，重点关注与四个项目中每一个项目相关的途径。该核心的创新方面包括以下内容：a) 开发独特的肺生物储存库来自 ARDS 患者的 Mφ 样本，包括来自一部分患者的纵向样本以进行表征 ARDS 阶段肺 Mφ 群体的变化；b) 患者肺 Mφ 的 scRNA-seq 分析，与最近的其他研究相比，Mφ 分析在方法上取得了重大进展；利用 NBBAL 方法可大大增强样本收集，因为它可以安全且可靠地执行呼吸治疗师和其他受训者的高产出； d) 将患者结合在一起的集成核心结构利用生物统计和生物信息专业知识和资源采集样本，以最大限度地提高利用效率这些临床数据；e) 从代表性不足的不同 ICU 患者群体中收集样本；研究不足的群体（30-40% 非洲裔美国人和 30-40% 西班牙裔/拉丁裔患者） f) 比较。去除循环 PBMC 后 ARDS 患者肺 Mφ 群体中的表达谱淋巴细胞，这将改善报告的这些样本类型之间的不良相关性；免疫麻痹作为患者样本的表型特征，过去从未对其进行过评估 ARDS AMφ 临床样本的研究；h) 加强对脓毒症和肺炎引起的 ARDS 的关注；以强化肺 Mφ 分析为特征的主要病因。