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: 10382633
• 负责人: VASILIS VASILIOU
• 金额: $ 14.82万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382633
• 关键词: Alcohol-Induced Disorders; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcoholic liver damage; Alcohols; Animal Model; Biochemical; Biochemical Pathway; Biological; Biological Markers; Cell physiology; Cells; Chronic; Complex; Coupled; Data; Data Analyses; Data Analytics; Detection; Development; Diagnosis; Diagnostic; Drug or chemical Tissue Distribution; Early Diagnosis; Early treatment; Ethanol; Fatty Liver; Fibrosis; Foundations; Functional disorder; Future; General Population; Goals; Heavy Drinking; Hepatitis; Hepatocyte; Histologic; Histology; Human; Hybrids; Image; Individual; Inflammation; Investigation; Knowledge; Label; Link; Lipids; Liquid substance; Liver; Liver Cirrhosis; Liver diseases; Machine Learning; Maps; Mass Spectrum Analysis; Metabolic; Molecular; Molecular Profiling; Molecular Structure; Monoclonal Antibody R24; National Institute on Alcohol Abuse and Alcoholism; Pathogenicity; Pathologic; Pathway interactions; Pattern; Phase; Plasma; Process; Proteomics; Publishing; Recovery; Resources; Risk; Sampling; Signal Pathway; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Steatohepatitis; Structure; System; Tissue imaging; Tissues; alcohol abuse therapy; alcohol research; biobank; biomarker identification; candidate marker; cohort; diagnostic biomarker; effective therapy; global health; human subject; improved; insight; intrahepatic; liver biopsy; liver imaging; metabolome; metabolomics; molecular imaging; mouse model; novel; novel diagnostics; novel marker; potential biomarker; predictive marker; protein metabolite; screening; small molecule; sobriety; specific biomarkers; tissue injury; tool

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 的 诱导 流感样 治疗 健康， 1,919,430 社会 人 2019冠状病毒病。 疾病 意味 感染 极其 冷却器， SARS-CoV-2 .我们建议确定 经历不同严重程度COVID-19的患者的血浆代谢组。这种变化 应该是关键的，可以预测患者COVID-19症状的严重程度，并提供 关于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，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 IMPACT Biorepository系统。这个储存库储存了人类标本， 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。的董事 生物贮藏库是本补充报告的共同研究者。因此，我们处于独特的位置来执行这部小说 （a）进行代谢组学分析的基础设施，而且我们已经 制定了方法，（B）获得储存在IMPACT的COVID-19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）生物储存库（和 相关的患者记录），（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。 在本补充中 目前由SARS-CoV-2引起的大流行是主要关注的，因为（i）它具有高度传染性，（ii）它 一系列不利健康后果（统称为COVID-19），从轻度 症状（发烧，发冷，咳嗽）危及生命的肺炎和SARS，以及（iii）没有有效的 到目前为止，SARS-CoV-2大流行对公众造成了毁灭性的影响， 感染者的国际死亡率为5.8%。截至2020年6月6日，美国已 例，死亡率5.7%。为遏制这一流行病而采取的措施使正常的 活动和削弱国家和国际经济。在大流行的早期阶段， 有特定基础医疗条件的个人更容易受到 最近，很明显，年轻的，表面上健康的人可能携带 并可能屈服于/进展为COVID-19的更严重表现。目前尚无 可靠地预测个体COVID-19症状的严重程度（或COVID-19的病程） SARS-CoV-2这是一个严重的知识赤字。如果有这样的信息， 有助于对患者进行分类并允许更有效地利用有限的卫生资源，例如， 重症监护室病床和医务人员。N 或与COVID-19的各个阶段相关的 o研究调查了由以下因素引起的代谢改变：

项目成果

COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy.

• DOI: 10.1186/s40246-021-00326-3
• 发表时间: 2021-05-10
• 期刊: Human genomics
• 影响因子: 4.5
• 作者: Novelli G;Biancolella M;Mehrian-Shai R;Colona VL;Brito AF;Grubaugh ND;Vasiliou V;Luzzatto L;Reichardt JKV
• 通讯作者: Reichardt JKV