Networking metabolites, diseases, and drugs

초록

Understanding how the breakdown of cellular processes leads to a single or multiple diseases is one of the major challenges of our century. Local perturbations in cellular processes may spread to adjacent or often more distant processes 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. In the cellular metabolism, inactive or non-expressed metabolic enzymes due to genetic defects may cause the accumulation of toxic metabolites or the absence of essential metabolites, leading to metabolic diseases, and thus become the targets of 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. Further- more, 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.