%0 Journal Article %1 Hase2009Structure %A Hase, Takeshi %A Tanaka, Hiroshi %A Suzuki, Yasuhiro %A Nakagawa, So %A Kitano, Hiroaki %D 2009 %I Public Library of Science %J PLoS Comput Biol %K drug-discovery network-analyses organisation protein-protein-interactions %N 10 %P e1000550+ %R 10.1371/journal.pcbi.1000550 %T Structure of Protein Interaction Networks and Their Implications on Drug Design %U http://dx.doi.org/10.1371/journal.pcbi.1000550 %V 5 %X 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. Genome-wide data on interactions between proteins are now available, and networks of protein interactions are the keys to understanding diseases and finding accurate drug targets. This study revealed that the architectural properties of the backbones of protein interaction networks (PINs) were similar to those of the Internet router-level topology by using statistical analyses of genome-wide budding yeast and human PINs. This type of network is known as a highly optimized tolerance (HOT) network that is robust against failures in its components and that ensures high levels of communication. Moreover, we also found that a large number of the most successful drug-target proteins are on the backbone of the human PIN. We made a list of proteins on the backbone of the human PIN, which may help drug companies to search more efficiently for new drug targets.

@article{Hase2009Structure, 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. Genome-wide data on interactions between proteins are now available, and networks of protein interactions are the keys to understanding diseases and finding accurate drug targets. This study revealed that the architectural properties of the backbones of protein interaction networks ({PINs}) were similar to those of the Internet router-level topology by using statistical analyses of genome-wide budding yeast and human {PINs}. This type of network is known as a highly optimized tolerance ({HOT}) network that is robust against failures in its components and that ensures high levels of communication. Moreover, we also found that a large number of the most successful drug-target proteins are on the backbone of the human {PIN}. We made a list of proteins on the backbone of the human {PIN}, which may help drug companies to search more efficiently for new drug targets.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Hase, Takeshi and Tanaka, Hiroshi and Suzuki, Yasuhiro and Nakagawa, So and Kitano, Hiroaki}, biburl = {https://www.bibsonomy.org/bibtex/2f9531f3f227220b5b93f1e2bd9c6277b/karthikraman}, citeulike-article-id = {6042110}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pcbi.1000550}, day = 30, doi = {10.1371/journal.pcbi.1000550}, interhash = {2adbcb5ff1f1b1712b273fe652eb9cd5}, intrahash = {f9531f3f227220b5b93f1e2bd9c6277b}, journal = {PLoS Comput Biol}, keywords = {drug-discovery network-analyses organisation protein-protein-interactions}, month = oct, number = 10, pages = {e1000550+}, posted-at = {2010-03-05 15:30:09}, priority = {2}, publisher = {Public Library of Science}, timestamp = {2018-12-02T16:09:07.000+0100}, 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 }