iLSGRN: inference of large-scale gene regulatory networks based on multi-model fusion.

MOTIVATION: Gene regulatory networks (GRNs) are a way of describing the interaction between genes, which contribute to revealing the different biological mechanisms in the cell. Reconstructing GRNs based on gene expression data has been a central computational problem in systems biology. However, due to the high dimensionality and non-linearity of large-scale GRNs, accurately and efficiently inferring GRNs is still a challenging task. RESULTS: In this article, we propose a new approach, iLSGRN, to reconstruct large-scale GRNs from steady-state and time-series gene expression data based on non-linear ordinary differential equations. Firstly, the regulatory gene recognition algorithm calculates the Maximal Information Coefficient between genes and excludes redundant regulatory relationships to achieve dimensionality reduction. Then, the feature fusion algorithm constructs a model leveraging the feature importance derived from XGBoost (eXtreme Gradient Boosting) and RF (Random Forest) models, which can effectively train the non-linear ordinary differential equations model of GRNs and improve the accuracy and stability of the inference algorithm. The extensive experiments on different scale datasets show that our method makes sensible improvement compared with the state-of-the-art methods. Furthermore, we perform cross-validation experiments on the real gene datasets to validate the robustness and effectiveness of the proposed method. AVAILABILITY AND IMPLEMENTATION: The proposed method is written in the Python language, and is available at: https://github.com/lab319/iLSGRN.

Playing Extensive Games with Learning of Opponent's Cognition.

Decision-making is a basic component of agents' (e.g., intelligent sensors) behaviors, in which one's cognition plays a crucial role in the process and outcome. Extensive games, a class of interactive decision-making scenarios, have been studied in diverse fields. Recently, a model of extensive games was proposed in which agent cognition of the structure of the underlying game and the quality of the game situations are encoded by artificial neural networks. This model refines the classic model of extensive games, and the corresponding equilibrium concept-cognitive perfect equilibrium (CPE)-differs from the classic subgame perfect equilibrium, since CPE takes agent cognition into consideration. However, this model neglects the consideration that game-playing processes are greatly affected by agents' cognition of their opponents. To this end, in this work, we go one step further by proposing a framework in which agents' cognition of their opponents is incorporated. A method is presented for evaluating opponents' cognition about the game being played, and thus, an algorithm designed for playing such games is analyzed. The resulting equilibrium concept is defined as adversarial cognition equilibrium (ACE). By means of a running example, we demonstrate that the ACE is more realistic than the CPE, since it involves learning about opponents' cognition. Further results are presented regarding the computational complexity, soundness, and completeness of the game-solving algorithm and the existence of the equilibrium solution. This model suggests the possibility of enhancing an agent's strategic ability by evaluating opponents' cognition.

TIVC: An Efficient Local Search Algorithm for Minimum Vertex Cover in Large Graphs.

The minimum vertex cover (MVC) problem is a canonical NP-hard combinatorial optimization problem aiming to find the smallest set of vertices such that every edge has at least one endpoint in the set. This problem has extensive applications in cybersecurity, scheduling, and monitoring link failures in wireless sensor networks (WSNs). Numerous local search algorithms have been proposed to obtain "good" vertex coverage. However, due to the NP-hard nature, it is challenging to efficiently solve the MVC problem, especially on large graphs. In this paper, we propose an efficient local search algorithm for MVC called TIVC, which is based on two main ideas: a 3-improvements (TI) framework with a tiny perturbation and edge selection strategy. We conducted experiments on real-world large instances of a massive graph benchmark. Compared with three state-of-the-art MVC algorithms, TIVC shows superior performance in accuracy and possesses a remarkable ability to identify significantly smaller vertex covers on many graphs.

Molecular mechanism and diagnostic marker investigation of endoplasmic reticulum stress on periodontitis.

PURPOSE: The aim of this study was to reveal the biological function of endoplasmic reticulum stress (ERS)-related genes (ERSGs) in periodontitis, and provide potential ERS diagnostic markers for clinical therapy of periodontitis. METHODS: The differentially expressed ERSGs (DE-ERSGs) were reveled based on periodontitis-related microarray dataset in Gene Expression Omnibus (GEO) database and 295 ERS in previous study, followed by a protein-protein interaction network construction. Then, the subtypes of periodontitis were explored, followed by validation with immune cell infiltration and gene set enrichment. Two machine learning algorithms were used to reveal potential ERS diagnostic markers of periodontitis. The diagnostic effect, target drug and immune correlation of these markers were further evaluated. Finally, a microRNA(miRNA)-gene interaction network was constructed. RESULTS: A total of 34 DE-ERSGs were revealed between periodontitis samples and control, followed by two subtypes investigated. There was a significant difference of ERS score, immune infiltration and Hallmark enrichment between two subtypes. Then, totally 7 ERS diagnostic markers including FCGR2B, XBP1, EDEM2, ATP2A3, ERLEC1, HYOU1 and YOD1 were explored, and the v the time-dependent ROC analysis showed a reliable result. In addition, a drug-gene network was constructed with 4 up-regulated ERS diagnostic markers and 24 drugs. Finally, based on 32 interactions, 5 diagnostic markers and 20 miRNAs, a miRNA-target network was constructed. CONCLUSIONS: Up-regulated miR-671-5p might take part in the progression of periodontitis via stimulating the expression of ATP2A3. ERSGs including XBP1 and FCGR2B might be novel diagnostic marker for periodontitis.

Cross-Inhibitor: a time-sensitive molecular circuit based on DNA strand displacement.

Designing biochemical systems that can be effectively used in diverse fields, including diagnostics, molecular computing and nanomachines, has long been recognized as an important goal of molecular programming and DNA nanotechnology. A key issue in the development of such practical devices on the nanoscale lies in the development of biochemical components with information-processing capacity. In this article, we propose a molecular device that utilizes DNA strand displacement networks and allows interactive inhibition between two input signals; thus, it is termed a cross-inhibitor. More specifically, the device supplies each input signal with a processor such that the processing of one input signal will interdict the signal of the other. Biochemical experiments are conducted to analyze the interdiction performance with regard to effectiveness, stability and controllability. To illustrate its feasibility, a biochemical framework grounded in this mechanism is presented to determine the winner of a tic-tac-toe game. Our results highlight the potential for DNA strand displacement cascades to act as signal controllers and event triggers to endow molecular systems with the capability of controlling and detecting events and signals.

On Metric Dimension in Some Hex Derived Networks.

The concept of a metric dimension was proposed to model robot navigation where the places of navigating agents can change among nodes. The metric dimension m d ( G ) of a graph G is the smallest number k for which G contains a vertex set W, such that | W | = k and every pair of vertices of G possess different distances to at least one vertex in W. In this paper, we demonstrate that m d ( H D N 1 ( n ) ) = 4 for n ≥ 2 . This indicates that in these types of hex derived sensor networks, the least number of nodes needed for locating any other node is four.

Boosting Reinforcement Learning via Hierarchical Game Playing With State Relay.

Due to its wide application, deep reinforcement learning (DRL) has been extensively studied in the motion planning community in recent years. However, in the current DRL research, regardless of task completion, the state information of the agent will be reset afterward. This leads to a low sample utilization rate and hinders further explorations of the environment. Moreover, in the initial training stage, the agent has a weak learning ability in general, which affects the training efficiency in complex tasks. In this study, a new hierarchical reinforcement learning (HRL) framework dubbed hierarchical learning based on game playing with state relay (HGR) is proposed. In particular, we introduce an auxiliary penalty to regulate task difficulty, and one training mechanism, the state relay mechanism, is designed. The relay mechanism can make full use of the intermediate states of the agent and expand the environment exploration of low-level policy. Our algorithm can improve the sample utilization rate, reduce the sparse reward problem, and thereby enhance the training performance in complex environments. Simulation tests are carried out on two public experiment platforms, i.e., MazeBase and MuJoCo, to verify the effectiveness of the proposed method. The results show that HGR significantly benefits the reinforcement learning (RL) area.

An Operational DNA Strand Displacement Encryption Approach.

DeoxyriboNucleic Acid (DNA) encryption is a new encryption method that appeared along with the research of DNA nanotechnology in recent years. Due to the complexity of biology in DNA nanotechnology, DNA encryption brings in an additional difficulty in deciphering and, thus, can enhance information security. As a new approach in DNA nanotechnology, DNA strand displacement has particular advantages such as being enzyme free and self-assembly. However, the existing research on DNA-strand-displacement-based encryption has mostly stayed at a theoretical or simulation stage. To this end, this paper proposes a new DNA-strand-displacement-based encryption framework. This encryption framework involves three main strategies. The first strategy was a tri-phase conversion from plaintext to DNA sequences according to a Huffman-coding-based transformation rule, which enhances the concealment of the information. The second strategy was the development of DNA strand displacement molecular modules, which produce the initial key for information encryption. The third strategy was a cyclic-shift-based operation to extend the initial key long enough, and thus increase the deciphering difficulty. The results of simulation and biological experiments demonstrated the feasibility of our scheme for encryption. The approach was further validated in terms of the key sensitivity, key space, and statistic characteristic. Our encryption framework provides a potential way to realize DNA-strand-displacement-based encryption via biological experiments and promotes the research on DNA-strand-displacement-based encryption.

Partition Independent Set and Reduction-Based Approach for Partition Coloring Problem.

Given a graph whose vertex set is partitioned, the partition coloring problem (PCP) requires the selection of one vertex from each partite set, such that the subgraph induced by the set of the selected vertices has the minimum chromatic number. Motivated by the routing and wavelength assignment problem for optical networks, PCP has been used to model many other real-world applications, such as dichotomy-based constraint encoding and scheduling problems. Solving PCP for large graphs is still a challenge since it is NP -complete. In this article, we first propose a key concept called a partition independent set (PIS) and design an efficient algorithm called FastPIS to find a maximum PIS. By applying FastPIS with a simple coloring procedure, we can obtain a high-quality initial solution for PCP. Moreover, we propose a reduction rule based on another novel concept called an l -clustering-degree bound ordered set ( l -CDBOS), by which the scale of the working graph can be iteratively reduced. Based on these techniques, we develop an efficient method called HotPGC for solving PCP. The proposed algorithm is evaluated on benchmark graphs, and computational results show that HotPGC achieves highly competitive performance, compared with the state-of-the-art algorithms. The influence of the proposed reduction rule on the efficiency of HotPGC is also analyzed.