title: Verification and optimal control of context-sensitive probabilistic Boolean networks using model checking and polynomial optimization.
abstract: One of the significant topics in systems biology is to develop control theory of gene regulatory networks (GRNs). In typical control of GRNs, expression of some genes is inhibited (activated) by manipulating external stimuli and expression of other genes. It is expected to apply control theory of GRNs 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 GRNs, and gene expression is expressed by a binary value (ON or OFF). In particular, a context-sensitive probabilistic Boolean network (CS-PBN), which is one of the extended models of BNs, is used. For CS-PBNs, the verification problem and the optimal control problem are considered. For the verification problem, a solution method using the probabilistic model checker PRISM is proposed. For the optimal control problem, a solution method using polynomial optimization is proposed. Finally, a numerical example on the WNT5A network, which is related to melanoma, is presented. The proposed methods provide us useful tools in control theory of GRNs.
authors.affiliation: School of Information Science, Japan Advanced Institute of Science and Technology, Ishikawa 923-1292, Japan.
authors.forename: Koichi
authors.identifier: 0000-0002-3358-0254
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: School of Information Science, Japan Advanced Institute of Science and Technology, Ishikawa 923-1292, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hiraishi
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D007254:Information Science / Q000379:methods*; D008957:Models, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein