Pinning controllability of autonomous Boolean control networks

Autonomous Boolean networks (ABNs), which are developed to model the Boolean networks (BNs) with regulatory delays, are well known for their advantages of characterizing the intrinsic evolution rules of biological systems such as the gene regulatory networks. As a special type of ABNs with binary inputs, the autonomous Boolean control networks (ABCNs) are introduced for designing and analyzing the therapeutic intervention strategies where the binary inputs represent whether a certain medicine is dominated or not. An important problem in the therapeutic intervention is to design a control sequence steering an ABCN from an undesirable location (implying a diseased state) to a desirable one (corresponding to a healthy state). Motivated by such background, this paper aims to investigate the reachability and controllability of ABCNs with pinning controllers. Several necessary and sufficient criteria are provided by resorting to the semi-tensor product techniques of matrices. Moreover, an effective pinning control algorithm is presented for steering an ABCN from any given states to the desired state in the shortest time period. Numerical examples are also presented to demonstrate the results obtained.This work was supported in part by National Natural Science Foundation of China (Grant Nos. 61329301, 61273156), Natural Science Foundation of Jiangsu Province of China (Grant No. BK20130017), Six Talent Peaks Project for the High Level Personnel from the Jiangsu Province of China (Grant No. 2015- DZXX-003), Scientific Research Foundations of Graduate School of Southeast University (Grant No. YBJJ1560), and Innovation Program of Jiangsu Province (Grant No. KYZZ15 0050)

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

Mining and state-space modeling and verification of sub-networks from large-scale biomolecular networks

<p>Abstract</p> <p>Background</p> <p>Biomolecular networks dynamically respond to stimuli and implement cellular function. Understanding these dynamic changes is the key challenge for cell biologists. As biomolecular networks grow in size and complexity, the model of a biomolecular network must become more rigorous to keep track of all the components and their interactions. In general this presents the need for computer simulation to manipulate and understand the biomolecular network model.</p> <p>Results</p> <p>In this paper, we present a novel method to model the regulatory system which executes a cellular function and can be represented as a biomolecular network. Our method consists of two steps. First, a novel scale-free network clustering approach is applied to the large-scale biomolecular network to obtain various sub-networks. Second, a state-space model is generated for the sub-networks and simulated to predict their behavior in the cellular context. The modeling results represent <it>hypotheses </it>that are tested against high-throughput data sets (microarrays and/or genetic screens) for both the natural system and perturbations. Notably, the dynamic modeling component of this method depends on the automated network structure generation of the first component and the sub-network clustering, which are both essential to make the solution tractable.</p> <p>Conclusion</p> <p>Experimental results on time series gene expression data for the human cell cycle indicate our approach is promising for sub-network mining and simulation from large-scale biomolecular network.</p

Finding and Analyzing the Minimum Set of Driver Nodes in Control of Boolean Networks

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State Estimation for Stochastic Time-Varying Boolean Networks

National Key R&D Program of China (Grant Number: 2018YFB1003800); 10.13039/501100001809-National Natural Science Foundation of China (Grant Number: 61673110, 61873148 and 61933007); Shanghai Sailing Program (Grant Number: 19YF1402400); 10.13039/501100006249-Donghua University (Grant Number: 104-07-0053019); Alexander von Humboldt Foundation of Germany

High-Level Analysis of the Impact of Soft-Faults in Cyberphysical Systems

As digital systems grow in complexity and are used in a broader variety of safety-critical applications, there is an ever-increasing demand for assessing the dependability and safety of such systems, especially when subjected to hazardous environments. As a result, it is important to identify and correct any functional abnormalities and component faults as early as possible in order to minimize performance degradation and to avoid potential perilous situations. Existing techniques often lack the capacity to perform a comprehensive and exhaustive analysis on complex redundant architectures, leading to less than optimal risk evaluation. Hence, an early analysis of dependability of such safety-critical applications enables designers to develop systems that meets high dependability requirements. Existing techniques in the field often lack the capacity to perform full system analyses due to state-explosion limitations (such as transistor and gate-level analyses), or due to the time and monetary costs attached to them (such as simulation, emulation, and physical testing). In this work we develop a system-level methodology to model and analyze the effects of Single Event Upsets (SEUs) in cyberphysical system designs. The proposed methodology investigates the impacts of SEUs in the entire system model (fault tree level), including SEU propagation paths, logical masking of errors, vulnerability to specific events, and critical nodes. The methodology also provides insights on a system's weaknesses, such as the impact of each component to the system's vulnerability, as well as hidden sources of failure, such as latent faults. Moreover, the proposed methodology is able to identify and categorize the system's components in order of criticality, and to evaluate different approaches to the mitigation of such criticality (in the form of different configurations of TMR) in order to obtain the most efficient mitigation solution available. The proposed methodology is also able to model and analyze system components individually (system component level), in order to more accurately estimate the component's vulnerability to SEUs. In this case, a more refined analysis of the component is conducted, which enables us to identify the source of the component's criticality. Thereafter, a second mitigation mechanic (internal to the component) takes place, in order to evaluate the gains and costs of applying different configurations of TMR to the component internally. Finally, our approach will draw a comparison between the results obtained at both levels of analysis in order to evaluate the most efficient way of improving the targeted system design

Towards the control of cell states in gene regulatory networks by evolving Boolean networks

Biological cell behaviours emerge from complex patterns of interactions between genes and their products, known as gene regulatory networks (GRNs). More specifically, GRNs are complex dynamical structures that orchestrate the activities of biological cells by governing the expression of mRNA and proteins. Many computational models of these networks have been shown to be able to carry out complex computation in an efficient and robust manner, particularly in the domains of control and signal processing. GRNs play a central role within living organisms and efficient strategies for controlling their dynamics need to be developed. For instance, the ability to push a cell towards or away from certain behaviours, is an important aim in fields such as medicine and synthetic biology. This could, for example, help to find novel approaches in the design of therapeutic drugs. However, current approaches to controlling these networks exhibit poor scalability and limited generality. This thesis proposes a new approach and an alternative method for performing state space targeting in GRNs, by coupling an artificial GRN to an existing GRN. This idea is tested in simulation by coupling together Boolean networks that represent controlled and controller systems. Evolutionary algorithms are used to evolve the controller Boolean networks. Controller Boolean networks are applied to a range of controlled Boolean networks including Boolean models of actual biological circuits, each with different dynamics. The results show that controller Boolean networks can be optimised to control trajectories in the target networks. Also, the approach scales well as the target network size increases. The use of Boolean modelling is potentially advantageous from an implementation perspective, since synthetic biology techniques can be used to refine an optimised controller Boolean network into an in vivo form, which could then control a genetic network directly from within a cell