Abstract
BackgroundAbnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective.ResultsWe applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism.ConclusionThere are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism.
Highlights
Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor
Among the 36 critical driver metabolites, 27 metabolites are essential, which suggests that the critical driver metabolites play important roles in the human liver metabolism
We find that the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems
Summary
Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. With the accumulation of the relevant data, it becomes feasible to study metabolic systems in a genome-scale. A human metabolic model has been reconstructed based on genomic and bibliomic data [6]. The reconstructed genome-scale human metabolic model has been used to study human physiology and pathology [7]. Even if the dissatisfaction exist, studies on these models could uncover novel valuable information on metabolic systems based on network analysis [11,12]. It is rewarding to study the metabolic systems from the perspective of networks
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