A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease
Summary: 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...
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2021
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oai:doaj.org-article:4779fe95c0d5444893ef3db3e78f48442021-11-20T05:08:26ZA network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease2589-004210.1016/j.isci.2021.103222https://doaj.org/article/4779fe95c0d5444893ef3db3e78f48442021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221011901https://doaj.org/toc/2589-0042Summary: 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 genome-scale 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.Hong YangMuhammad ArifMeng YuanXiangyu LiKoeun ShongHasan TürkezJens NielsenMathias UhlénJan BorénCheng ZhangAdil MardinogluElsevierarticleHepatologyGene networkSystems biologyScienceQENiScience, Vol 24, Iss 11, Pp 103222- (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Hepatology Gene network Systems biology Science Q |
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Hepatology Gene network Systems biology Science Q Hong Yang Muhammad Arif Meng Yuan Xiangyu Li Koeun Shong Hasan Türkez Jens Nielsen Mathias Uhlén Jan Borén Cheng Zhang Adil Mardinoglu A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| description |
Summary: 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 genome-scale 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. |
| format |
article |
| author |
Hong Yang Muhammad Arif Meng Yuan Xiangyu Li Koeun Shong Hasan Türkez Jens Nielsen Mathias Uhlén Jan Borén Cheng Zhang Adil Mardinoglu |
| author_facet |
Hong Yang Muhammad Arif Meng Yuan Xiangyu Li Koeun Shong Hasan Türkez Jens Nielsen Mathias Uhlén Jan Borén Cheng Zhang Adil Mardinoglu |
| author_sort |
Hong Yang |
| title |
A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| title_short |
A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| title_full |
A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| title_fullStr |
A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| title_full_unstemmed |
A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| title_sort |
network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/4779fe95c0d5444893ef3db3e78f4844 |
| work_keys_str_mv |
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