Distinctive Behaviors of Druggable Proteins in Cellular Networks.
The interaction environment of a protein in a cellular network is important in defining the role that the protein plays in the system as a whole, and thus its potential suitability as a drug target. Despite the importance of the network environment, it is neglected during target selection for drug d...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-12-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1004597 |
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| author | Costas Mitsopoulos Amanda C Schierz Paul Workman Bissan Al-Lazikani |
| author_facet | Costas Mitsopoulos Amanda C Schierz Paul Workman Bissan Al-Lazikani |
| author_sort | Costas Mitsopoulos |
| collection | DOAJ |
| description | The interaction environment of a protein in a cellular network is important in defining the role that the protein plays in the system as a whole, and thus its potential suitability as a drug target. Despite the importance of the network environment, it is neglected during target selection for drug discovery. Here, we present the first systematic, comprehensive computational analysis of topological, community and graphical network parameters of the human interactome and identify discriminatory network patterns that strongly distinguish drug targets from the interactome as a whole. Importantly, we identify striking differences in the network behavior of targets of cancer drugs versus targets from other therapeutic areas and explore how they may relate to successful drug combinations to overcome acquired resistance to cancer drugs. We develop, computationally validate and provide the first public domain predictive algorithm for identifying druggable neighborhoods based on network parameters. We also make available full predictions for 13,345 proteins to aid target selection for drug discovery. All target predictions are available through canSAR.icr.ac.uk. Underlying data and tools are available at https://cansar.icr.ac.uk/cansar/publications/druggable_network_neighbourhoods/. |
| format | Article |
| id | doaj-art-a53beb667763457b803138d85697cd89 |
| institution | DOAJ |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2015-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-a53beb667763457b803138d85697cd892025-08-20T03:10:02ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582015-12-011112e100459710.1371/journal.pcbi.1004597Distinctive Behaviors of Druggable Proteins in Cellular Networks.Costas MitsopoulosAmanda C SchierzPaul WorkmanBissan Al-LazikaniThe interaction environment of a protein in a cellular network is important in defining the role that the protein plays in the system as a whole, and thus its potential suitability as a drug target. Despite the importance of the network environment, it is neglected during target selection for drug discovery. Here, we present the first systematic, comprehensive computational analysis of topological, community and graphical network parameters of the human interactome and identify discriminatory network patterns that strongly distinguish drug targets from the interactome as a whole. Importantly, we identify striking differences in the network behavior of targets of cancer drugs versus targets from other therapeutic areas and explore how they may relate to successful drug combinations to overcome acquired resistance to cancer drugs. We develop, computationally validate and provide the first public domain predictive algorithm for identifying druggable neighborhoods based on network parameters. We also make available full predictions for 13,345 proteins to aid target selection for drug discovery. All target predictions are available through canSAR.icr.ac.uk. Underlying data and tools are available at https://cansar.icr.ac.uk/cansar/publications/druggable_network_neighbourhoods/.https://doi.org/10.1371/journal.pcbi.1004597 |
| spellingShingle | Costas Mitsopoulos Amanda C Schierz Paul Workman Bissan Al-Lazikani Distinctive Behaviors of Druggable Proteins in Cellular Networks. PLoS Computational Biology |
| title | Distinctive Behaviors of Druggable Proteins in Cellular Networks. |
| title_full | Distinctive Behaviors of Druggable Proteins in Cellular Networks. |
| title_fullStr | Distinctive Behaviors of Druggable Proteins in Cellular Networks. |
| title_full_unstemmed | Distinctive Behaviors of Druggable Proteins in Cellular Networks. |
| title_short | Distinctive Behaviors of Druggable Proteins in Cellular Networks. |
| title_sort | distinctive behaviors of druggable proteins in cellular networks |
| url | https://doi.org/10.1371/journal.pcbi.1004597 |
| work_keys_str_mv | AT costasmitsopoulos distinctivebehaviorsofdruggableproteinsincellularnetworks AT amandacschierz distinctivebehaviorsofdruggableproteinsincellularnetworks AT paulworkman distinctivebehaviorsofdruggableproteinsincellularnetworks AT bissanallazikani distinctivebehaviorsofdruggableproteinsincellularnetworks |