Global stabilizing control of large-scale biomolecular regulatory networks. 2023

Sugyun An, and So-Yeong Jang, and Sang-Min Park, and Chun-Kyung Lee, and Hoon-Min Kim, and Kwang-Hyun Cho
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

Cellular behavior is determined by complex non-linear interactions between numerous intracellular molecules that are often represented by Boolean network models. To achieve a desired cellular behavior with minimal intervention, we need to identify optimal control targets that can drive heterogeneous cellular states to the desired phenotypic cellular state with minimal node intervention. Previous attempts to realize such global stabilization were based solely on either network structure information or simple linear dynamics. Other attempts based on non-linear dynamics are not scalable. Here, we investigate the underlying relationship between structurally identified control targets and optimal global stabilizing control targets based on non-linear dynamics. We discovered that optimal global stabilizing control targets can be identified by analyzing the dynamics between structurally identified control targets. Utilizing these findings, we developed a scalable global stabilizing control framework using both structural and dynamic information. Our framework narrows down the search space based on strongly connected components and feedback vertex sets then identifies global stabilizing control targets based on the canalization of Boolean network dynamics. We find that the proposed global stabilizing control is superior with respect to the number of control target nodes, scalability, and computational complexity. We provide a GitHub repository that contains the DCGS framework written in Python as well as biological random Boolean network datasets (https://github.com/sugyun/DCGS). Supplementary data are available at Bioinformatics online.

UI MeSH Term Description Entries
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D017711 Nonlinear Dynamics The study of systems which respond disproportionately (nonlinearly) to initial conditions or perturbing stimuli. Nonlinear systems may exhibit "chaos" which is classically characterized as sensitive dependence on initial conditions. Chaotic systems, while distinguished from more ordered periodic systems, are not random. When their behavior over time is appropriately displayed (in "phase space"), constraints are evident which are described by "strange attractors". Phase space representations of chaotic systems, or strange attractors, usually reveal fractal (FRACTALS) self-similarity across time scales. Natural, including biological, systems often display nonlinear dynamics and chaos. Chaos Theory,Models, Nonlinear,Non-linear Dynamics,Non-linear Models,Chaos Theories,Dynamics, Non-linear,Dynamics, Nonlinear,Model, Non-linear,Model, Nonlinear,Models, Non-linear,Non linear Dynamics,Non linear Models,Non-linear Dynamic,Non-linear Model,Nonlinear Dynamic,Nonlinear Model,Nonlinear Models,Theories, Chaos,Theory, Chaos
D053263 Gene Regulatory Networks Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations. Gene Circuits,Gene Modules,Gene Networks,Transcriptional Networks,Gene Module,Circuit, Gene,Circuits, Gene,Gene Circuit,Gene Network,Gene Regulatory Network,Module, Gene,Modules, Gene,Network, Gene,Network, Gene Regulatory,Network, Transcriptional,Networks, Gene,Networks, Gene Regulatory,Networks, Transcriptional,Regulatory Network, Gene,Regulatory Networks, Gene,Transcriptional Network

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