We study a decentralized control problem of discrete event systems with communication. We first give a general automata-theoretic formalism that enables us to handle various types of communication, including delay. The decentralized control problem is shown to be undecidable under this formalism. Next we propose a semi-decision procedure for computing finite-state controllers to achieve a given specification in the sense of bisimilarity between the controlled system and a given specification. Using this procedure, we prove decidability of the problem for two special cases, one is the case in which the communication behavior is given as k -bounded-delay communication, and the other is the case in which any cycle in the state transition diagram of the system contains an event observable by all controllers. We also show a method for optimizing controllers based on a graph problem.

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.

Control of gene regulatory networks is one of the fundamental topics in systems biology. In the last decade, control theory of Boolean networks (BNs), which is well known as a model of gene regulatory networks, has been widely studied. In this review paper, our previously proposed methods on optimal control of probabilistic Boolean networks (PBNs) are introduced. First, the outline of PBNs is explained. Next, an optimal control method using polynomial optimization is explained. The finite-time optimal control problem is reduced to a polynomial optimization problem. Furthermore, another finite-time optimal control problem, which can be reduced to an integer programming problem, is also explained.

Boolean networks (BNs) play a crucial role in modeling and analyzing biological systems. One of the central issues in the analysis of BNs is attractor detection, i.e., identification of all possible attractors. This problem becomes more challenging for large asynchronous random Boolean networks (ARBNs) because of the asynchronous and non-deterministic updating scheme. In this paper, we present and formally prove several relations between feedback vertex sets (FVSs) and dynamics of BNs. From these relations, we propose an FVS-based method for detecting attractors in ARBNs. Our approach relies on the principle of removing arcs in the state transition graph to get a candidate set and the reachability property to filter the candidate set. We formally prove the correctness of our method and show its efficiency by conducting experiments on real biological networks and randomly generated N-K networks. The obtained results are very promising since our method can handle large networks whose sizes are up to 101 without using any network reduction technique.

In recent years, Boolean-network-model-based approaches to dynamical analysis of complex biological networks such as gene regulatory networks have been extensively studied. One of the fundamental problems in control theory of such networks is the problem of determining whether a given substance quantity can be arbitrarily controlled by operating the other substance quantities, which we call the controllability problem. This paper proposes a polynomial-time algorithm for solving this problem. Although the algorithm is based on a sufficient condition for controllability, it is easily computable for a wider class of large-scale biological networks compared with the existing approaches. A key to this success in our approach is to give up computing Boolean operations in a rigorous way and to exploit an adjacency matrix of a directed graph induced by a Boolean network. By applying the proposed approach to a neurotransmitter signaling pathway, it is shown that it is effective.