Predicting transcription factors in human alcoholic hepatitis from gene regulatory network.

OBJECTIVE Alcoholic hepatitis (AH) is a type of alcoholic liver disorder caused by overconsumption of alcohol. The involvement of several transcription factors (TF), as the main regulators of disease related gene expression has been documented previously. However, despite the importance of analysis of gene regulatory network for understanding the molecular basis in any disease, so far, there is no report on construction of such network for AH in human. MATERIALS AND METHODS Here, we used microarray analysis to construct a rather complete gene regulatory network and used it to predict TFs and pathways that affected by this disease. RESULTS Ten TFs were shown to undergo significant alteration in AH. These TFs are AR, EGR1, MYC, TCF4, ATF3, JUN, FOXO3, STAT1, HIF1A and EOMES, where ATF3, TCF4 and MYC are the new TFs with a role in AH. Comparisons of gene expression profile of patients with those of healthy persons indicates 820 differentially expressed (DE) genes. Network analysis indicates that, these ten TFs regulate expression of 516 DE genes (out of 820 genes), by 1057 interactions. Furthermore, we report pathways that significantly affected by these ten TFs. CONCLUSIONS These results may contribute to our limited understanding of the molecular basis of AH.