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Robustness and Evolvability of the Human Signaling Network
Date Issued
2014-07-31
Date Available
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.
Sponsorship
Science Foundation Ireland
Other Sponsorship
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
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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Robustness and Evolvability of the Human Signaling Network.PDF
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1.47 MB
Format
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