MDN MDN. (a) Construction of the MDN. (Upper) A local region of the glycolysis, where the catalytic enzymes are shown with red background and their corresponding.

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MDN MDN. (a) Construction of the MDN. (Upper) A local region of the glycolysis, where the catalytic enzymes are shown with red background and their corresponding genes are shown with orange background. (Lower) A local neighborhood of the metabolic diseases (blue) associated with the shown reactions. The gene ENO3 encodes the enzyme catalyzing the conversion between phosphoenolpyruvate and glycerate-2P, and its mutation is involved in the development of enolase-β deficiency. The gene products of PGAM2 and BPGM, catalyzing the reaction involving glycerate-2P and glycerate-3P, are connected to myopathy and hemolytic anemia. Then the two diseases are not only connected with each other but also linked to enolase-β deficiency due to the adjacency of their associated reactions. (b) In the network representation, 308 nonisolated diseases (nodes) are connected by 878 metabolic links combining the potential links predicted by KEGG and OMIM reconstructions. The color of the nodes indicates the disease class (see SI Text and Dataset S1), and node size is proportional to the prevalence of each disease in the Medicare dataset. The width of the link between diseases is proportional to the comorbidity C of the two connected diseases. We show with red the links with significant (P < 0.01) comorbidity. Clusters of diseases associated with purine metabolism (blue shading), fatty acid metabolism (red shading), and porphyrin metabolism (green shading) are shown. Lee D. et.al. PNAS 2008;105:9880-9885 © 2008 by The National Academy of Sciences of the USA