Identification of Biomarkers and Novel Pathways of Alcoholic Liver Disease by Leveraging Metabolomics, Tissue Imaging Mass Spectrometry, and Integrative Machine Learning
Identification of Biomarkers and Novel Pathways of Alcoholic Liver Disease by Leveraging Metabolomics, Tissue Imaging Mass Spectrometry, and Integrative Machine Learning
批准号:
10382633
负责人:
VASILIS VASILIOU
金额:
$14.82万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-04-10 至 2023-03-31
关键词:
Alcohol-Induced DisordersAlcoholic HepatitisAlcoholic Liver DiseasesAlcoholic liver damageAlcoholsAnimal ModelBiochemicalBiochemical PathwayBiologicalBiological MarkersCell physiologyCellsChronicComplexCoupledDataData AnalysesData AnalyticsDetectionDevelopmentDiagnosisDiagnosticDrug or chemical Tissue DistributionEarly DiagnosisEarly treatmentEthanolFatty LiverFibrosisFoundationsFunctional disorderFutureGeneral PopulationGoalsHeavy DrinkingHepatitisHepatocyteHistologicHistologyHumanHybridsImageIndividualInflammationInvestigationKnowledgeLabelLinkLipidsLiquid substanceLiverLiver CirrhosisLiver diseasesMachine LearningMapsMass Spectrum AnalysisMetabolicMolecularMolecular ProfilingMolecular StructureMonoclonal Antibody R24National Institute on Alcohol Abuse and AlcoholismPathogenicityPathologicPathway interactionsPatternPhasePlasmaProcessProteomicsPublishingRecoveryResourcesRiskSamplingSignal PathwaySourceSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSteatohepatitisStructureSystemTissue imagingTissuesalcohol abuse therapyalcohol researchbiobankbiomarker identificationcandidate markercohortdiagnostic biomarkereffective therapyglobal healthhuman subjectimprovedinsightintrahepaticliver biopsyliver imagingmetabolomemetabolomicsmolecular imagingmouse modelnovelnovel diagnosticsnovel markerpotential biomarkerpredictive markerprotein metabolitescreeningsmall moleculesobrietyspecific biomarkerstissue injurytool
中文摘要
摘要
的
诱导
流感样
治疗
健康,
1,919,430
社会
人
新冠肺炎。
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。
本补充
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不同阶段相关的疾病
o研究调查了由以下因素引起的代谢改变:
英文摘要
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
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
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
Administrative Core
-
批准号:10361890
-
项目类别:
-
资助金额:$17.36万
-
财政年份:2022
-
负责人:VASILIS VASILIOU
-
依托单位:
Emerging Water Contaminants: Investigating and Mitigating Exposures and Health Risks
-
批准号:10361885
-
项目类别:
-
资助金额:$188.29万
-
财政年份:2022
-
负责人:VASILIS VASILIOU
-
依托单位:
Emerging Water Contaminants: Investigating and Mitigating Exposures and Health Risks
-
批准号:10698003
-
项目类别:
-
资助金额:$134.98万
-
财政年份:2022
-
负责人:VASILIS VASILIOU
-
依托单位:
Administrative Core
-
批准号:10698032
-
项目类别:
-
资助金额:$12.89万
-
财政年份:2022
-
负责人:VASILIS VASILIOU
-
依托单位:
Identification of Biomarkers and Novel Pathways of Alcoholic Liver Disease by Leveraging Metabolomics, Tissue Imaging Mass Spectrometry, and Integrative Machine Learning
-
批准号:10221329
-
项目类别:
-
资助金额:$15.06万
-
财政年份:2020
-
负责人:VASILIS VASILIOU
-
依托单位:
Summer Research Experience in Environmental Health (SREEH)
-
批准号:10112911
-
项目类别:
-
资助金额:$10.6万
-
财政年份:2019
-
负责人:VASILIS VASILIOU
-
依托单位:
Glutathione Monoesters to Counteract Ocular Chemical Injury
-
批准号:9001771
-
项目类别:
-
资助金额:$40.28万
-
财政年份:2015
-
负责人:VASILIS VASILIOU
-
依托单位:
The role of GSH in cornea and lens development
-
批准号:8891008
-
项目类别:
-
资助金额:$13.26万
-
财政年份:2014
-
负责人:VASILIS VASILIOU
-
依托单位:
The role of ALDH1B1 in ethanol metabolism and colon cancer
-
批准号:8704693
-
项目类别:
-
资助金额:$43.92万
-
财政年份:2014
-
负责人:VASILIS VASILIOU
-
依托单位:
A Novel Aldehyde Dehydrogenase (ALDH16A1) in Gout
-
批准号:8634470
-
项目类别:
-
资助金额:$18.37万
-
财政年份:2014
-
负责人:VASILIS VASILIOU
-
依托单位:
Role and Molecular Mechanisms of Corneal Aldehyde Dehydrogenase
-
批准号:8891010
-
项目类别:
-
资助金额:$15.51万
-
财政年份:2014
-
负责人:VASILIS VASILIOU
-
依托单位:
The role of ALDH1B1 in ethanol metabolism and colon cancer
-
批准号:8930903
-
项目类别:
-
资助金额:$42.25万
-
财政年份:2014
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models for Alcohol Metabolism and Tissue Injury
-
批准号:8603827
-
项目类别:
-
资助金额:$2.06万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models and Metabolomics Tools to Investigate Alcohol Metabolism and Tissue Injury
-
批准号:10474322
-
项目类别:
-
资助金额:$51.12万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models for Alcohol Metabolism and Tissue Injury
-
批准号:8676404
-
项目类别:
-
资助金额:$2.21万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models for Alcohol Metabolism and Tissue Injury
-
批准号:8891009
-
项目类别:
-
资助金额:$26.99万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models for Alcohol Metabolism and Tissue Injury
-
批准号:9233873
-
项目类别:
-
资助金额:$24.59万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models and Metabolomics Tools to Investigate Alcohol Metabolism and Tissue Injury
-
批准号:10002403
-
项目类别:
-
资助金额:$41.88万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models for Alcohol Metabolism and Tissue Injury
-
批准号:9054035
-
项目类别:
-
资助金额:$28.97万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
Mouse Models and Metabolomics Tools to Investigate Alcohol Metabolism and Tissue Injury
-
批准号:10231089
-
项目类别:
-
资助金额:$51.12万
-
财政年份:2013
-
负责人:VASILIS VASILIOU
-
依托单位:
海外基金