Study of Non-Alcoholic Fatty Liver Disease Using a Novel Enrichment Analysis That Integrates Transcriptomics and Metabolite Concentrations Data

to steatohepatitis (NASH), and rarely, progression to liver cirrhosis. Molecular interactions of NAFLD are poorly understood and its analysis requires a detailed understanding of the underlying metabolic and regulatory processes on the molecular level. Thus, to understand the molecular interactions of NAFLD, we developed a novel method we call minimal network enrichment analysis (MiNEA), and we performed MiNEA using constraints inferred from metabolite concentrations and transcriptomics data from a NASH mouse model system.

Furthermore, we compare whether the molecular interactions of NAFLD differ between mouse and human, we also performed the MiNEA analysis using transcriptomics data from humans with NASH. In both human and mouse oxidative stress pathways are found to be upregulated through superoxide anion synthesis in NASH phenotype. Additionally, in mouse, synthesis of ceramide is identified as upregulated in steatosis but downregulated in NASH. Glutamine synthesis is upregulated in mouse steatosis, while it is downregulated in human NASH.