Towards whole‐body systems physiology

Abstract

Mol Syst Biol. 6: 409 The liver executes a multitude of functions in human physiology such as detoxification or hormone synthesis. Consequently, hepatic dysfunction, be it inborn or acquired, can lead to diverse pathological manifestations as for instance argininemia or hypercholesterolemia. To analyze liver function at the cellular scale and to investigate underlying genotype–phenotype relationships, a growing number of high‐throughput data has been generated in recent years. However, mechanistic computational models are equally important in order to interpret and contextualize this data and to obtain a holistic understanding of human liver functionality per se . In a first attempt to capture human metabolism in a rigorous quantitative sense, two generic stoichiometric models at genome scale have been developed recently (Duarte et al , 2007; Ma et al , 2007). They correlate pathway information with gene annotation thereby describing basic metabolic biochemistry. These models successfully identified selected drug targets, whereas investigation of tissue‐specific metabolism was only possible by additionally considering gene‐expression measurements, which revealed flux activity of disease‐related enzymes in different organs (Shlomi et al , 2008). This approach, however, cannot compensate for the lacking tissue‐specific metabolic networks, which are essential to …