A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic liver disease
Journal article, 2021
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. We performed network analysis to investigate the dysregulated biological processes in the disease progression and revealed the molecular mechanism underlying NAFLD. Based on network analysis, we identified a highly conserved disease-associated gene module across three different NAFLD cohorts and highlighted the predominant role of key transcriptional regulators associated with lipid and cholesterol metabolism. In addition, we revealed the detailed metabolic differences between heterogeneous NAFLD patients through integrative systems analysis of transcriptomic data and liver-specific genomescale metabolic model. Furthermore, we identified transcription factors (TFs), including SREBF2, HNF4A, SREBF1, YY1, and KLF13, showing regulation of hepatic expression of genes in the NAFLD-associated modules and validated the TFs using data generated from a mouse NAFLD model. In conclusion, our integrative analysis facilitates the understanding of the regulatory mechanism of these perturbed TFs and their associated biological processes.
Author
Hong Yang
Royal Institute of Technology (KTH)
Muhammad Arif
Royal Institute of Technology (KTH)
Meng Yuan
Royal Institute of Technology (KTH)
Xiangyu Li
Royal Institute of Technology (KTH)
Koeun Shong
Royal Institute of Technology (KTH)
Hasan Turkez
Atatürk University
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
BioInnovation Institute
Mathias Uhlen
Royal Institute of Technology (KTH)
Jan Boren
University of Gothenburg
C. Zhang
Royal Institute of Technology (KTH)
Zhengzhou University
Adil Mardinoglu
King's College London
Royal Institute of Technology (KTH)
iScience
25890042 (eISSN)
Vol. 24 11 103222Subject Categories
Medical Genetics
Bioinformatics and Systems Biology
Genetics
DOI
10.1016/j.isci.2021.103222
PubMed
34712920