Robustness and Evolvability of the Human Signaling Network
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Title: | Robustness and Evolvability of the Human Signaling Network | Authors: | Kim, Junil; Vandamme, Drieke; Kim, Jeong-Rae; Garcia Munoz, Amaya; Kolch, Walter; Cho, Kwang-Hyun | Permanent link: | http://hdl.handle.net/10197/9162 | Date: | 31-Jul-2014 | Online since: | 2018-01-11T12:42:00Z | Abstract: | Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores. | Funding Details: | Science Foundation Ireland | Funding Details: | National Research Foundation of Korea Korean Government |
Type of material: | Journal Article | Publisher: | Public Library of Science | Journal: | PLoS Computational Biology | Volume: | 10 | Issue: | 7 | Start page: | 5041 | End page: | 5058 | Copyright (published version): | 2014 the Authors | Keywords: | Human signaling network; Boolean network modeling; Attractor landscape analysis | DOI: | 10.1371/journal.pcbi.1003763 | Language: | en | Status of Item: | Peer reviewed | This item is made available under a Creative Commons License: | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ |
Appears in Collections: | Conway Institute Research Collection SBI Research Collection Medicine Research Collection |
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