ArticlePLoS computational biology2014
Robustness and evolvability of the human signaling network.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Normalizing Input-Output Relationships of Cancer Networks for Reversion Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Antifragility Predicts the Robustness and Evolvability of Biological Networks through Multi-Class Classification with a Convolutional Neural Network.Entropy (Basel, Switzerland) · 2020Article
- Minimal intervening control of biomolecular networks leading to a desired cellular state.Scientific reports · 2019Article
- Systems biology in hepatology: approaches and applications.Nature reviews. Gastroenterology & hepatology · 2018Review
- Sharing of Phosphatases Promotes Response Plasticity in Phosphorylation Cascades.Biophysical journal · 2018Article
- How the evolution of multicellularity set the stage for cancer.British journal of cancer · 2018Review
- Differential Tissue-specific and Pathway-specific Anti-obesity Effects of Green Tea and Taeumjowitang, a Traditional Korean Medicine, in Mice.Journal of cancer prevention · 2017Article
- Attractor landscape analysis of colorectal tumorigenesis and its reversion.BMC systems biology · 2016Article
- The reverse control of irreversible biological processes.Wiley interdisciplinary reviews. Systems biology and medicine · 2016Review
- Complex regulation of Hsf1-Skn7 activities by the catalytic subunits of PKA in Saccharomyces cerevisiae: experimental and computational evidences.BMC systems biology · 2015Article
- Multiscale analysis of the murine intestine for modeling human diseases.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation.Scientific reports · 2015Article
- Increased signaling entropy in cancer requires the scale-free property of protein interaction networks.Scientific reports · 2015Article
- Therapeutic control and resistance of the EGFR-driven signaling network in glioblastoma.Cell communication and signaling : CCS · 2015Review
Corrections and comments
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Authors and funding
6 authors.
Funding
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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.
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