Transcriptomics of Liver in Alcoholic Hepatitis

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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.