Gene

Biological network

Hepatocellular carcinoma

Biology

Liver disease

Systems biology

Cirrhosis

Cancer research

Biochemistry

Fatty liver

Computational biology

Drug discovery

Immunology

Physics

Bioinformatics

Optics

Internal medicine

Hepatology

Crosstalk

Gut flora

Biological pathway

Medicine

Disease

Gene expression

Pathology

Nature Reviews Gastroenterology & Hepatology

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. Biological network models can provide a scaffold for studying the biological pathways operating in connection with disease development. Here, the authors review how biological network models can integrate multiomics data to advance our understanding of complex liver diseases, which might lead to improved treatment strategies.

Systems biology in hepatology: approaches and applications