Transcriptomics of Liver in Alcoholic Hepatitis

酒精性肝炎肝脏转录组学

• 批准号: 8427259
• 负责人: CHAD P GARNER
• 金额: $ 25.19万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8427259
• 关键词: Alcoholic Hepatitis; Alcoholic Liver Cirrhosis; Biological; California; Characteristics; Clinical; Clinical Markers; Clinical Trials; Complement; Data; Enrollment; Gene Expression; Gene Expression Profile; Gene Proteins; Genes; Genetic Transcription; Liver; Measurement; Measures; Mutation; Mycophenolate; Outcome; Participant; Pathway interactions; Patients; Proteomics; RNA Sequences; Randomized; Sampling; Severity of illness; Technology; Testing; Tissue Sample; Tissues; Transcript; Translating; Translational Research; Variant; Vertebral column; Work; base; comparison group; computing resources; design; outcome forecast; protein expression; public health relevance; research study; response; transcriptomics; treatment response

DESCRIPTION (provided by applicant): The experiments proposed in this component are designed to characterize the transcriptome of the alcoholic hepatitis liver and identify expressed genes and transcripts that are markers of disease severity, response to treatment and prognosis. Full transcriptomes will be measured using RNA-seq technology. Two hypotheses are the basis of the proposed experiments. The transcriptomes of livers from alcoholic hepatitis patients have measureable quantitative expression characteristics that distinguish them from the liver transcriptomes of alcoholic cirrhosis patients and healthy liver tissue. The clinical features, treatment response and prognosis of alcoholic hepatitis patients can be attributed to variation in the transcriptomes of their liver tissue. Furthermore, the expression markers will be correlated with biologically related proteomic markers. We will measure the transcriptomes of liver tissue samples taken from 30 alcoholic hepatitis patients with Lille scores < 0.45, 30 alcoholic hepatitis patients with Lille scores e 0.45, 30 alcoholic cirrhosis patients, and 30 matched normal samples to identify an alcoholic hepatitis-specific transcription profile. In parallel with this work, we will measure the transcriptomes of liver tissue sampled from 150 alcoholic hepatitis patients at enrollment in a clinical trial and identify gene and transcript expression markers of treatment-related clinical outcomes and prognosis. This work will generate sets of transcripts, genes, functional mutations, pathways, and gene-protein networks that are characteristic of alcoholic hepatitis and markers for the clinical outcomes and prognosis of alcoholic hepatitis patients. Although this project is largely agnostic and discovery-based it i important translational research that highly complements the other U01 projects in the consortium. We will identify gene and transcript expression markers of the alcoholic hepatitis liver and identify markers of treatment response and prognosis in the alcoholic hepatitis liver transcriptome.

描述（由申请人提供）：本部分提出的实验旨在表征酒精性肝炎肝脏的转录组，并确定作为疾病严重程度、治疗反应和预后标记的表达基因和转录本。完整的转录组将使用RNA-seq技术进行测量。两个假设是提出的实验的基础。酒精性肝炎患者肝脏转录组具有可测量的定量表达特征，将其与酒精性肝硬化患者和健康肝组织的肝脏转录组区分开来。酒精性肝炎患者的临床特征、治疗反应和预后可归因于其肝组织转录组的变异。此外，表达标记将与生物学相关的蛋白质组学标记相关联。我们将测量30例Lille评分< 0.45的酒精性肝炎患者、30例Lille评分为0.45的酒精性肝炎患者、30例酒精性肝硬化患者和30例匹配正常样本的肝组织样本的转录组，以确定酒精性肝炎特异性转录谱。与此同时，我们将在临床试验中测量150名酒精性肝炎患者肝组织样本的转录组，并确定与治疗相关的临床结果和预后的基因和转录表达标记。这项工作将产生一系列的转录本、基因、功能突变、途径和基因-蛋白质网络，这些都是酒精性肝炎的特征，也是酒精性肝炎患者临床结果和预后的标志。虽然这个项目在很大程度上是不可知的和基于发现的，但它是重要的转化研究，高度补充了财团中的其他U01项目。我们将确定酒精性肝炎肝脏的基因和转录表达标记，并确定酒精性肝炎肝脏转录组中治疗反应和预后的标记。