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Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis

From the perspective of systems science, tumorigenesis can be hypothesized as a critical transition (an abrupt shift from one state to another) between proliferative and apoptotic attractors on the state space of a molecular interaction network, for which an attractor is defined as a stable state to...

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Autores principales: Chu, Hyunho, Lee, Daewon, Cho, Kwang-Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595005/
https://www.ncbi.nlm.nih.gov/pubmed/26439385
http://dx.doi.org/10.1371/journal.pone.0140172
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author Chu, Hyunho
Lee, Daewon
Cho, Kwang-Hyun
author_facet Chu, Hyunho
Lee, Daewon
Cho, Kwang-Hyun
author_sort Chu, Hyunho
collection PubMed
description From the perspective of systems science, tumorigenesis can be hypothesized as a critical transition (an abrupt shift from one state to another) between proliferative and apoptotic attractors on the state space of a molecular interaction network, for which an attractor is defined as a stable state to which all initial states ultimately converge, and the region of convergence is called the basin of attraction. Before the critical transition, a cellular state might transit between the basin of attraction for an apoptotic attractor and that for a proliferative attractor due to the noise induced by the inherent stochasticity in molecular interactions. Such a flickering state transition (state transition between the basins of attraction for alternative attractors from the impact of noise) would become more frequent as the cellular state approaches near the boundary of the basin of attraction, which can increase the variation in the estimate of the respective basin size. To investigate this for colorectal tumorigenesis, we have constructed a stochastic Boolean network model of the molecular interaction network that contains an important set of proteins known to be involved in cancer. In particular, we considered 100 representative sequences of 20 gene mutations that drive colorectal tumorigenesis. We investigated the appearance of cancerous cells by examining the basin size of apoptotic, quiescent, and proliferative attractors along with the sequential accumulation of gene mutations during colorectal tumorigenesis. We introduced a measure to detect the flickering state transition as the variation in the estimate of the basin sizes for three-phenotype attractors from the impact of noise. Interestingly, we found that this measure abruptly increases before a cell becomes cancerous during colorectal tumorigenesis in most of the gene mutation sequences under a certain level of stochastic noise. This suggests that a frequent flickering state transition can be a precritical phenomenon of colorectal tumorigenesis.
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spelling pubmed-45950052015-10-09 Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis Chu, Hyunho Lee, Daewon Cho, Kwang-Hyun PLoS One Research Article From the perspective of systems science, tumorigenesis can be hypothesized as a critical transition (an abrupt shift from one state to another) between proliferative and apoptotic attractors on the state space of a molecular interaction network, for which an attractor is defined as a stable state to which all initial states ultimately converge, and the region of convergence is called the basin of attraction. Before the critical transition, a cellular state might transit between the basin of attraction for an apoptotic attractor and that for a proliferative attractor due to the noise induced by the inherent stochasticity in molecular interactions. Such a flickering state transition (state transition between the basins of attraction for alternative attractors from the impact of noise) would become more frequent as the cellular state approaches near the boundary of the basin of attraction, which can increase the variation in the estimate of the respective basin size. To investigate this for colorectal tumorigenesis, we have constructed a stochastic Boolean network model of the molecular interaction network that contains an important set of proteins known to be involved in cancer. In particular, we considered 100 representative sequences of 20 gene mutations that drive colorectal tumorigenesis. We investigated the appearance of cancerous cells by examining the basin size of apoptotic, quiescent, and proliferative attractors along with the sequential accumulation of gene mutations during colorectal tumorigenesis. We introduced a measure to detect the flickering state transition as the variation in the estimate of the basin sizes for three-phenotype attractors from the impact of noise. Interestingly, we found that this measure abruptly increases before a cell becomes cancerous during colorectal tumorigenesis in most of the gene mutation sequences under a certain level of stochastic noise. This suggests that a frequent flickering state transition can be a precritical phenomenon of colorectal tumorigenesis. Public Library of Science 2015-10-06 /pmc/articles/PMC4595005/ /pubmed/26439385 http://dx.doi.org/10.1371/journal.pone.0140172 Text en © 2015 Chu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chu, Hyunho
Lee, Daewon
Cho, Kwang-Hyun
Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis
title Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis
title_full Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis
title_fullStr Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis
title_full_unstemmed Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis
title_short Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis
title_sort precritical state transition dynamics in the attractor landscape of a molecular interaction network underlying colorectal tumorigenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595005/
https://www.ncbi.nlm.nih.gov/pubmed/26439385
http://dx.doi.org/10.1371/journal.pone.0140172
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