人类代谢网络与疾病关联性研究.pdf

The implications of human metabolic network topology for disease comorbidity † † ‡ § ‡ ´ †¶ D.-S. Lee* , J. Park* , K. A. Kay , N. A. Christakis , Z. N. Oltvai , and A.-L. Barabasi* *Center for Complex Network Research and Department of Physics, Biology, and Computer Science, Northeastern University, Boston, MA 02115; †Center for Cancer Systems Biology, Dana–Farber Cancer Institute, Boston, MA 02115; ‡Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261; and §Department of Health Care Policy, Harvard Medical School, Boston, MA 02115 Edited by H. Eugene Stanley, Boston University, Boston, MA, and approved May 1, 2008 (received for review March 4, 2008) Most diseases are the consequence of the breakdown of cellular amino acid, or fatty acid metabolism, organic acidemias, lysosomal processes, but the relationships among genetic/epigenetic defects, storage diseases, and so on. However, the effect of these enzyme the molecular interaction networks underlying them, and the disease defects (especially in their more subtle forms) may not always be phenotypes remain poorly understood. To gain insights into such confined to the metabolic reactions they catalyze. Cellular metab- relationships, here we constructed a bipartite human disease associ- olism represents the integrated interconversion of thousands of ation network in which nodes are diseases and two diseases are metabolic substrates through enzyme-catalyzed biochemical reac- linked if mutated enzymes associated with them catalyze adjacent tions (16, 19–21). Thus, sets of consecutive reactions are function- metabolic reactions. We find that connected disease pairs display ally interrelated, and their activities (i.e. their flux