Patient Sampling and Genomics Core

患者采样和基因组学核心

• 批准号: 10701927
• 负责人: STEVEN M DUDEK
• 金额: $ 35.93万
• 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/10701927
• 关键词: Acute; Acute Lung Injury; Acute Respiratory Distress Syndrome; African American; Bioinformatics; Biometry; Blood; Blood specimen; Bronchoalveolar Lavage; Categories; Clinical; Clinical Data; Code; Critical Illness; Data; Development; Diagnostic; Disease Outcome; Doctor of Philosophy; Enrollment; Etiology; Excision; Genomics; Hispanic; Human; Human Resources; Immune Tolerance; Individual; Inflammatory; Informatics; Institution; Institutional Review Boards; Latino; Lung; Lymphocyte; Macrophage; 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; Syndrome; Underrepresented Populations; Universities; Work; biobank; clinical database; clinical phenotype; improved; innovation; lung injury; novel strategies; patient population; patient subsets; professor; programs; repaired; repository; respiratory; sample collection; sepsis induced ARDS; 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 本计划项目的一个关键翻译部分涉及巨噬细胞的相关分析(Mφ) 从患有败血症、肺炎和其他急性侮辱的危重患者分离出来，这些侮辱会导致 毁灭性的急性呼吸窘迫综合征(ARDS)临床综合征。病人的样本和 基因组学核心(核心D)将履行收集这些M个φ样本并建立和 维护疾病严重程度的临床数据库。获取足够样本进行建议的可行性 通过广泛使用非支气管镜BAL(NBBAL)方法， 其诊断结果与支气管镜BAL相似，在危重患者中具有极好的安全性 需要机械通风的病人。此外，还将采集血液进行外周血液分离 取单个核细胞(PBMC)，与肺标本进行比较。纵向样本将从一个 患者的子集。此外，Core D将提供对这些临床样本的生物统计分析以及 对所有项目的样本进行生物信息学分析，包括散装RNA-seq分析和单细胞rna-seq分析 (scRNA-seq)处理和分析，如个别项目中所述。一系列临床严重程度将 将疾病转归与M-φS的流式细胞术、转录和功能分析相关联， 重点关注与四个项目中的每个项目相关的路径。 该核心的创新方面包括：a)开发一种独特的肺生物储存库 来自急性呼吸窘迫综合征患者的M个φ样本，包括来自患者子集的纵向样本以表征 急性呼吸窘迫综合征患者肺M-φ的单链RNA序列分析 与最近的其他研究相比，Mφ分析在方法学上有了实质性的进步；c)广泛 利用NBBAL方法大大加强样本收集，因为它可以安全和 呼吸治疗师和其他受训人员的高产出；d)将患者 利用生物统计学和生物信息学专业知识和资源获取样本，以最大限度地提高利用率 这些临床数据；e)从不同的ICU患者群体中收集样本 研究不足的群体(30-40%的非裔美国人和30-40%的西班牙裔/拉丁裔患者)。F)比较 急性呼吸窘迫综合征患者去除外周血单核细胞后肺M-φ细胞的表达 淋巴细胞，这将改善所报告的这些样本类型之间相关性较差的情况；g)纳入 免疫麻痹作为患者样本的表型特征，这在过去还没有得到评估 对急性呼吸窘迫综合征AMφ临床样本的研究；h)加强对脓毒症和肺炎所致急性呼吸窘迫综合征的关注 以强化肺M-φ分析为特征的原发病因。