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