Identification of Biomarkers and Novel Pathways of Alcoholic Liver Disease by Leveraging Metabolomics, Tissue Imaging Mass Spectrometry, and Integrative Machine Learning

利用代谢组学、组织成像质谱和综合机器学习鉴定酒精性肝病的生物标志物和新途径

• 批准号: 10221329
• 负责人: VASILIS VASILIOU
• 金额: $ 15.06万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-10 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221329
• 关键词: 2019-nCoV; Alcoholic Liver Diseases; Beds; Bilirubin; Biological Markers; COVID-19; Cardiac; Clinical; Coagulation Process; Communicable Diseases; Connecticut; Coronavirus; Coughing; Data; Disease; Environmental Health; Family; Female; Ferritin; Fever; Fever Chills; Fibrin fragment D; Funding; Future; Genome; Health; Health Personnel; Health Resources; Hospitals; Human; Immunology; Individual; Infectious Disease Immunology; Infrastructure; Inpatients; International; Knowledge; Laboratories; Length of Stay; Life; Lung diseases; Machine Learning; Mass Spectrum Analysis; Measures; Medical; Metabolic; Methodology; Modeling; Molecular Profiling; Monoclonal Antibody R24; National Institute on Alcohol Abuse and Alcoholism; Outpatients; Paralysed; Pathway interactions; Patient Triage; Patients; Plasma; Pneumonia; Positioning Attribute; Predisposition; Preparation; Prothrombin time assay; Protocols documentation; Public Health; RNA Viruses; Records; Research; Research Personnel; Research Support; Reverse Transcriptase Polymerase Chain Reaction; Safety; Sampling; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Specimen; Statistical Data Interpretation; Symptoms; System; Tissue imaging; Triage; Vaccines; Ventilator; Viral; Viral Load result; Viral Respiratory Tract Infection; base; biobank; biomarker identification; cytokine; effective therapy; experience; flu; liver function; male; metabolome; metabolomics; metabolomics resource; mortality; novel; pandemic disease; prevent; repository; respiratory; stem; transmission process; virology

Abstract The induces flu-like treatment health, 1,919,430 societal people COVID-19. disease means infected extremely ventilators, SARS-CoV-2 . We propose to identify alterations in the plasma metabolome of patients experiencing different levels of severity of COVID-19. Such changes should be pivotal in allowing the prediction of the severity of the patient COVID-19 symptoms and also provide mechanistic information about the disease and its progression. In addition to our expertise in metabolomics, we are able to carry out this project because we have access to samples from the Yale New Haven Hospital System via the IMPACT Biorepository. This repository stores human specimens related to emerging respiratory viral infections (with a particular focus on COVID-19) in order to support research on factors related to viral expression, transmission, disease severity, progression, and susceptibility. The directors of the biorepository are co-investigators in this supplement. As such, we are in unique position to perform this novel research because we have: (a) the infrastructure to conduct the metabolomic analyses and we have already developed the methodologies, (b) access to COVID-19 patient plasma samples stored at the IMPACT (Implementing medical and public health actions against coronavirus in Connecticut) Biorepository (and associated patient records), (c) assembled an extraordinary team that includes expertise in metabolomics, virology, pulmonary and infectious disease, and immunology. of this supplement current pandemic caused by SARS-CoV-2 is of major concern because (i) it is highly contagious, (ii) it a spectrum of adverse health consequences (collectively known as COVID-19) that range from mild symptoms (fever, chills, cough) to life-endangering pneumonia and SARS, and (iii) there is no effective or vaccine to prevent it. To date, the SARS-CoV-2 pandemic has had devastating effects on public with an international mortality rate of 5.8% in infected individuals. As of June 6, 2020, the U.S. has cases and a mortality rate of 5.7%. Measures taken to stem the pandemic have paralyzed normal activities and crippled national and international economies. I n the early stages of the pandemic, older and individuals with specific underlying medical conditions were shown to be more vulnerable to More recently, it has become apparent that younger, ostensibly healthy individuals likely carry the and may succumb/progress to the more serious manifestations of COVID-19. Currently, there is no to reliably predict the severity of COVID-19 symptoms (or the course of COVID-19) in individuals by SARS-CoV-2 . This represents a significant knowledge deficit. Having such information would be helpful in triaging patients and allowing more efficient utilization of limited health resources, e.g., ICU beds, and medical personnel. N or that are associated with the various stages of COVID-19 o studies have investigated metabolic alterations caused by

抽象的 这 诱导 流感样 治疗 健康， 1,919,430 社会的 人们 新冠肺炎。 疾病 方法 已感染 极其 呼吸机， SARS-CoV-2 。我们建议确定以下方面的变更 经历不同严重程度的 COVID-19 患者的血浆代谢组。这样的改变 在预测患者 COVID-19 症状的严重程度方面应该至关重要，并且还可以提供 有关疾病及其进展的机制信息。除了我们在代谢组学方面的专业知识外，我们 能够开展这个项目是因为我们可以从耶鲁纽黑文医院获取样本 通过 IMPACT Biorepository 的系统。该存储库存储与新兴相关的人类标本 呼吸道病毒感染（特别关注 COVID-19），以支持相关因素的研究 病毒表达、传播、疾病严重程度、进展和易感性。该公司的董事 生物储存库是本增刊的共同研究者。因此，我们处于独特的位置来表演这部小说 研究，因为我们拥有：（a）进行代谢组学分析的基础设施，并且我们已经 开发了方法，(b) 获取 IMPACT 中存储的 COVID-19 患者血浆样本 （在康涅狄格州针对冠状病毒实施医疗和公共卫生行动）生物储存库（和 相关患者记录），(c) 组建了一支出色的团队，其中包括代谢组学方面的专业知识， 病毒学、肺部和传染病以及免疫学。 本补充品的 当前由 SARS-CoV-2 引起的大流行引起了人们的主要关注，因为 (i) 它具有高度传染性，(ii) 一系列不良健康后果（统称为 COVID-19），从轻度到 出现危及生命的肺炎和 SARS 症状（发烧、发冷、咳嗽），并且 (iii) 没有有效的治疗方法 或疫苗来预防。迄今为止，SARS-CoV-2 大流行已对公众造成毁灭性影响 国际感染者死亡率为 5.8%。截至2020年6月6日，美国已 病例数和死亡率为5.7%。为遏制疫情而采取的措施使正常生活陷入瘫痪 活动并削弱国家和国际经济。在大流行的早期阶段，老年人 患有特定基础疾病的个人更容易受到感染 最近，很明显，年轻、表面上健康的人可能携带 并可能会屈服/进展为更严重的 COVID-19 表现。目前，没有 可靠地预测个体中 COVID-19 症状的严重程度（或 COVID-19 的病程） 由 SARS-CoV-2 引起。这代表了严重的知识缺陷。拥有这样的信息将是 有助于对患者进行分类并更有效地利用有限的卫生资源，例如 ICU病床和医务人员。氮 或与 COVID-19 的各个阶段相关的 o 研究调查了以下原因引起的代谢改变