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• W2133191229 endingPage "53" @default.
• W2133191229 startingPage "53" @default.
• W2133191229 abstract "Understanding and ameliorating the effects of network damage are of significant interest, due in part to the variety of applications in which network damage is relevant. For example, the effects of genetic mutations can cascade through within-cell signaling and regulatory networks and alter the behavior of cells, possibly leading to a wide variety of diseases. The typical approach to mitigating network perturbations is to consider the compensatory activation or deactivation of system components. Here, we propose a complementary approach wherein interactions are instead modified to alter key regulatory functions and prevent the network damage from triggering a deregulatory cascade.We implement this approach in a Boolean dynamic framework, which has been shown to effectively model the behavior of biological regulatory and signaling networks. We show that the method can stabilize any single state (e.g., fixed point attractors or time-averaged representations of multi-state attractors) to be an attractor of the repaired network. We show that the approach is minimalistic in that few modifications are required to provide stability to a chosen attractor and specific in that interventions do not have undesired effects on the attractor. We apply the approach to random Boolean networks, and further show that the method can in some cases successfully repair synchronous limit cycles. We also apply the methodology to case studies from drought-induced signaling in plants and T-LGL leukemia and find that it is successful in both stabilizing desired behavior and in eliminating undesired outcomes. Code is made freely available through the software package BooleanNet.The methodology introduced in this report offers a complementary way to manipulating node expression levels. A comprehensive approach to evaluating network manipulation should take an all of the above perspective; we anticipate that theoretical studies of interaction modification, coupled with empirical advances, will ultimately provide researchers with greater flexibility in influencing system behavior." @default.
• W2133191229 created "2016-06-24" @default.
• W2133191229 creator A5012905268 @default.
• W2133191229 creator A5018738469 @default.
• W2133191229 date "2014-01-01" @default.
• W2133191229 modified "2023-10-12" @default.
• W2133191229 title "Stabilization of perturbed Boolean network attractors through compensatory interactions" @default.
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• W2133191229 doi "https://doi.org/10.1186/1752-0509-8-53" @default.
• W2133191229 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4037934" @default.
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• W2133191229 hasPublicationYear "2014" @default.
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