Systems biology in hepatology: approaches and applications

TY - JOUR

T1 - Systems biology in hepatology

T2 - approaches and applications

AU - Mardinoglu, Adil

AU - Boren, Jan

AU - Smith, Ulf

AU - Uhlen, Mathias

AU - Nielsen, Jens

PY - 2018/6

Y1 - 2018/6

N2 - Detailed insights into the biological functions of the liver and an understanding of its crosstalk with other human tissues and the gut microbiota can be used to develop novel strategies for the prevention and treatment of liver-associated diseases, including fatty liver disease, cirrhosis, hepatocellular carcinoma and type 2 diabetes mellitus. Biological network models, including metabolic, transcriptional regulatory, protein–protein interaction, signalling and co-expression networks, can provide a scaffold for studying the biological pathways operating in the liver in connection with disease development in a systematic manner. Here, we review studies in which biological network models were used to integrate multiomics data to advance our understanding of the pathophysiological responses of complex liver diseases. We also discuss how this mechanistic approach can contribute to the discovery of potential biomarkers and novel drug targets, which might lead to the design of targeted and improved treatment strategies. Finally, we present a roadmap for the successful integration of models of the liver and other human tissues with the gut microbiota to simulate whole-body metabolic functions in health and disease.

AB - Detailed insights into the biological functions of the liver and an understanding of its crosstalk with other human tissues and the gut microbiota can be used to develop novel strategies for the prevention and treatment of liver-associated diseases, including fatty liver disease, cirrhosis, hepatocellular carcinoma and type 2 diabetes mellitus. Biological network models, including metabolic, transcriptional regulatory, protein–protein interaction, signalling and co-expression networks, can provide a scaffold for studying the biological pathways operating in the liver in connection with disease development in a systematic manner. Here, we review studies in which biological network models were used to integrate multiomics data to advance our understanding of the pathophysiological responses of complex liver diseases. We also discuss how this mechanistic approach can contribute to the discovery of potential biomarkers and novel drug targets, which might lead to the design of targeted and improved treatment strategies. Finally, we present a roadmap for the successful integration of models of the liver and other human tissues with the gut microbiota to simulate whole-body metabolic functions in health and disease.

U2 - 10.1038/s41575-018-0007-8

DO - 10.1038/s41575-018-0007-8

M3 - Review article

SN - 1759-5045

VL - 15

SP - 365

EP - 377

JO - Nature Reviews Gastroenterology & Hepatology

JF - Nature Reviews Gastroenterology & Hepatology

IS - 6

ER -