Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses
Boolean networks (BNs) have been widely used as a useful model for molecular regulatory networks in systems biology. In the state space of BNs, attractors represent particular cell phenotypes. For targeted therapy of cancer, there is a pressing need to control the heterogeneity of cellular responses...
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doaj-260b24f89add4ff2924e3690bf6f885e2020-11-24T23:10:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-07-01910.3389/fphys.2018.00774358204Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular ResponsesJung-Min Yang0Chun-Kyung Lee1Kwang-Hyun Cho2School of Electronics Engineering, Kyungpook National University, Daegu, South KoreaSchool of Electronics Engineering, Kyungpook National University, Daegu, South KoreaLaboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South KoreaBoolean networks (BNs) have been widely used as a useful model for molecular regulatory networks in systems biology. In the state space of BNs, attractors represent particular cell phenotypes. For targeted therapy of cancer, there is a pressing need to control the heterogeneity of cellular responses to the targeted drug by reducing the number of attractors associated with the ill phenotypes of cancer cells. Here, we present a novel control scheme for global stabilization of BNs to a unique fixed point. Using a sufficient condition of global stabilization with respect to the adjacency matrix, we can determine a set of constant controls so that the controlled BN is steered toward an unspecified fixed point which can then be further transformed to a desired attractor by subsequent control. Our method is efficient in that it has polynomial complexity with respect to the number of state variables, while having exponential complexity with respect to in-degree of BNs. To demonstrate the applicability of the proposed control scheme, we conduct simulation studies using a regulation influence network describing the metastatic process of cells and the Mitogen-activated protein kinase (MAPK) signaling network that is crucial in cancer cell fate determination.https://www.frontiersin.org/article/10.3389/fphys.2018.00774/fullBoolean networks (BNs)global stabilizationsequential controlheterogeneitysystems biology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jung-Min Yang Chun-Kyung Lee Kwang-Hyun Cho |
spellingShingle |
Jung-Min Yang Chun-Kyung Lee Kwang-Hyun Cho Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses Frontiers in Physiology Boolean networks (BNs) global stabilization sequential control heterogeneity systems biology |
author_facet |
Jung-Min Yang Chun-Kyung Lee Kwang-Hyun Cho |
author_sort |
Jung-Min Yang |
title |
Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses |
title_short |
Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses |
title_full |
Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses |
title_fullStr |
Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses |
title_full_unstemmed |
Global Stabilization of Boolean Networks to Control the Heterogeneity of Cellular Responses |
title_sort |
global stabilization of boolean networks to control the heterogeneity of cellular responses |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2018-07-01 |
description |
Boolean networks (BNs) have been widely used as a useful model for molecular regulatory networks in systems biology. In the state space of BNs, attractors represent particular cell phenotypes. For targeted therapy of cancer, there is a pressing need to control the heterogeneity of cellular responses to the targeted drug by reducing the number of attractors associated with the ill phenotypes of cancer cells. Here, we present a novel control scheme for global stabilization of BNs to a unique fixed point. Using a sufficient condition of global stabilization with respect to the adjacency matrix, we can determine a set of constant controls so that the controlled BN is steered toward an unspecified fixed point which can then be further transformed to a desired attractor by subsequent control. Our method is efficient in that it has polynomial complexity with respect to the number of state variables, while having exponential complexity with respect to in-degree of BNs. To demonstrate the applicability of the proposed control scheme, we conduct simulation studies using a regulation influence network describing the metastatic process of cells and the Mitogen-activated protein kinase (MAPK) signaling network that is crucial in cancer cell fate determination. |
topic |
Boolean networks (BNs) global stabilization sequential control heterogeneity systems biology |
url |
https://www.frontiersin.org/article/10.3389/fphys.2018.00774/full |
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1725607800073093120 |