Human Metabolic Network and Disease Comorbidity

초록

Given that most diseases are the result of the breakdown of some cellular processes, a key aim of modern medicine is to establish the relationship between disease phenotypes and the various disruptions in the underlying cellular networks. Local perturbations in cellular processes may spread due to the intricate networking of cellular components. Such network effects at the molecular-interaction level may reappear in the patterns of disease occurrence and drug treatment. Here we show that our current understanding of the topology of the human metabolic network can provide insight into potential relationships among often distinct disease phenotypes and drugs.Using the known genetic defects associated with inherited diseases and the chemical similarity of drugs and metabolites, we construct a network of metabolites, metabolic diseases, and drugs. We find that the incidence of each metabolic disease, the comorbidity of each pair of diseases, and the number of drugs show significant correlations with the topological features, such as connectivity and network distance, of the associated metabolic enzymes in the metabolic network. Furthermore, the analysis of the modeled function of the human metabolic network offers a chance to discover new drug targets and understand the combinatorial drug effects. These results suggest that the structure and function of the metabolic network can have important consequences for disease diagnosis, treatment, and prevention.