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Network Modeling Approaches and Applications to Unravelling Non-Alcoholic Fatty Liver Disease

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Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA 90095, USA
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Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA 90095, USA
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Interdepartmental Program of Bioinformatics, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA 90095, USA
*
Author to whom correspondence should be addressed.
Genes 2019, 10(12), 966; https://doi.org/10.3390/genes10120966
Received: 22 October 2019 / Revised: 18 November 2019 / Accepted: 22 November 2019 / Published: 24 November 2019
(This article belongs to the Special Issue Current Advances in Network Biology for Disease Understanding)
Non-alcoholic fatty liver disease (NAFLD) is a progressive condition of the liver encompassing a range of pathologies including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Research into this disease is imperative due to its rapid growth in prevalence, economic burden, and current lack of FDA approved therapies. NAFLD involves a highly complex etiology that calls for multi-tissue multi-omics network approaches to uncover the pathogenic genes and processes, diagnostic biomarkers, and potential therapeutic strategies. In this review, we first present a basic overview of disease pathogenesis, risk factors, and remaining knowledge gaps, followed by discussions of the need and concepts of multi-tissue multi-omics approaches, various network methodologies and application examples in NAFLD research. We highlight the findings that have been uncovered thus far including novel biomarkers, genes, and biological pathways involved in different stages of NAFLD, molecular connections between NAFLD and its comorbidities, mechanisms underpinning sex differences, and druggable targets. Lastly, we outline the future directions of implementing network approaches to further improve our understanding of NAFLD in order to guide diagnosis and therapeutics. View Full-Text
Keywords: network modeling; integrative genomics; NAFLD; NASH; steatosis; systems biology; multi-omics network modeling; integrative genomics; NAFLD; NASH; steatosis; systems biology; multi-omics
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Blencowe, M.; Karunanayake, T.; Wier, J.; Hsu, N.; Yang, X. Network Modeling Approaches and Applications to Unravelling Non-Alcoholic Fatty Liver Disease. Genes 2019, 10, 966.

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