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

摘要 这个 归纳 流感样 治疗 健康， 1919430 社会性 人民 新冠肺炎。 疾病 手段 受感染的 极 通风器， SARS-CoV-2。我们建议确定以下变化： 不同严重程度新冠肺炎患者的血浆代谢产物。这样的变化 应该在预测患者新冠肺炎症状的严重性方面发挥关键作用，并提供 关于疾病及其进展的机械性信息。除了我们在代谢组学方面的专业知识外，我们 我们能够进行这个项目是因为我们可以从耶鲁纽黑文医院获得样本 系统通过Impact生物库。这个资料库存储了与新出现的人类标本有关的 呼吸道病毒感染(特别关注新冠肺炎)，以支持对相关因素的研究 病毒的表达、传播、疾病的严重性、进展和易感性。世界银行的董事们 生物信息库是本补充材料的共同调查者。因此，我们处于独特的地位来演绎这部小说 研究，因为我们有：(A)进行代谢分析的基础设施，我们已经 制定了方法学，(B)获取存储在IMPACT的新冠肺炎患者血浆样本 (在康涅狄格州实施针对冠状病毒的医疗和公共卫生行动)生物库(和 相关患者记录)，(C)组建了一个包括代谢组学专业知识的非凡团队， 病毒学、肺部和传染病以及免疫学。 本副刊的 目前由SARS-CoV-2引起的大流行令人担忧，因为(I)它具有高度传染性，(Ii)它 一系列对健康不利的后果(统称为新冠肺炎)，从轻微到轻微 症状(发烧、发冷、咳嗽)到危及生命的肺炎和SARS，以及(Iii)没有有效的 或疫苗来预防它。到目前为止，SARS-CoV-2大流行对公众造成了毁灭性的影响 全球感染者死亡率为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已使正常情况陷入瘫痪 经济活动和国家和国际经济陷入瘫痪。在大流行的早期阶段，年龄更大 而有特定潜在健康状况的人更容易患上 最近，越来越明显的是，更年轻、表面上健康的人可能会携带 并可能屈服于/进步于更严重的新冠肺炎表现。目前，没有 可靠地预测个体新冠肺炎症状(或新冠肺炎病程)的严重程度 被SARS-CoV-2感染。这代表着一种巨大的知识赤字。拥有这样的信息将是 有助于对患者进行分诊，并允许更有效地利用有限的卫生资源，例如， ICU床位和医务人员。N 或与新冠肺炎各个阶段相关的信息 O研究调查了由以下物质引起的代谢变化