Structure of Protein Interaction Networks and Their Implications on Drug Design Export

@article{citeulike:6042110, abstract = {Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects.}, author = {Hase, Takeshi and Tanaka, Hiroshi and Suzuki, Yasuhiro and Nakagawa, So and Kitano, Hiroaki}, citeulike-article-id = {6042110}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pcbi.1000550}, day = {30}, doi = {10.1371/journal.pcbi.1000550}, journal = {PLoS Comput Biol}, keywords = {disease\_drug, network\_analysis, network\_ppi}, month = {October}, number = {10}, pages = {e1000550+}, posted-at = {2009-11-02 07:02:06}, priority = {4}, publisher = {Public Library of Science}, title = {Structure of Protein Interaction Networks and Their Implications on Drug Design}, url = {http://dx.doi.org/10.1371/journal.pcbi.1000550}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:6042110 L3 - citeulike-article-id:6042110 N2 - Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects. IS - 10 JF - PLoS Comput Biol TI - Structure of Protein Interaction Networks and Their Implications on Drug Design PB - Public Library of Science VL - 5 SP - e1000550 KW - disease_drug KW - network_analysis KW - network_ppi AU - Hase, Takeshi AU - Tanaka, Hiroshi AU - Suzuki, Yasuhiro AU - Nakagawa, So AU - Kitano, Hiroaki PY - 2009/10/30/ UR - http://dx.doi.org/10.1371/journal.pcbi.1000550 ER -