Attractors in gene regulatory networks represent cell types or states of cells. In system biology and synthetic biology, it is important to generate gene regulatory networks with desired attractors. In this paper, we focus on a singleton attractor, which is also called a fixed point. Using a Boolean network (BN) model, we consider the problem of finding Boolean functions such that the system has desired singleton attractors and has no undesired singleton attractors. To solve this problem, we propose a matrix-based representation of BNs. Using this representation, the problem of finding Boolean functions can be rewritten as an Integer Linear Programming (ILP) problem and a Satisfiability Modulo Theories (SMT) problem. Furthermore, the effectiveness of the proposed method is shown by a numerical example on a WNT5A network, which is related to melanoma. The proposed method provides us a basic method for design of gene regulatory networks.
Developing control theory of gene regulatory networks is one of the significant topics in the field of systems biology, and it is expected to apply the obtained results to gene therapy technologies in the future. In this paper, a control method using a Boolean network (BN) is studied. A BN is widely used as a model of gene regulatory networks, and gene expression is expressed by a binary value (0 or 1). In the control problem, we assume that the concentration level of a part of genes is arbitrarily determined as the control input. However, there are cases that no gene satisfying this assumption exists, and it is important to consider structural control via external stimuli. Furthermore, these controls are realized by multiple drugs, and it is also important to consider multiple effects such as duration of effect and side effects. In this paper, we propose a BN model with two types of the control inputs and an optimal control method with duration of drug effectiveness. First, a BN model and duration of drug effectiveness are discussed. Next, the optimal control problem is formulated and is reduced to an integer linear programming problem. Finally, numerical simulations are shown.
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