Polynomial-Time Algorithm for Controllability Test of a Class of Boolean Biological Networks

<p/> <p>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.</p

Cell fate reprogramming by control of intracellular network dynamics

Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Here we develop a novel network control framework that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our approach drives any initial state to the target state with 100% effectiveness and needs to be applied only transiently for the network to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of helper T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments.Comment: 61 pages (main text, 15 pages; supporting information, 46 pages) and 12 figures (main text, 6 figures; supporting information, 6 figures). In revie

A weighted pair graph representation for reconstructibility of Boolean control networks

A new concept of weighted pair graphs (WPGs) is proposed to represent a new reconstructibility definition for Boolean control networks (BCNs), which is a generalization of the reconstructibility definition given in [Fornasini & Valcher, TAC2013, Def. 4]. Based on the WPG representation, an effective algorithm for determining the new reconstructibility notion for BCNs is designed with the help of the theories of finite automata and formal languages. We prove that a BCN is not reconstructible iff its WPG has a complete subgraph. Besides, we prove that a BCN is reconstructible in the sense of [Fornasini & Valcher, TAC2013, Def. 4] iff its WPG has no cycles, which is simpler to be checked than the condition in [Fornasini & Valcher, TAC2013, Thm. 4].Comment: 20 pages, 10 figures, accepted by SIAM Journal on Control and Optimizatio

Data based identification and prediction of nonlinear and complex dynamical systems

We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin