A comparative benchmarking and evaluation framework for heterogeneous network-based drug repositioning methods.

Computational drug repositioning, which involves identifying new indications for existing drugs, is an increasingly attractive research area due to its advantages in reducing both overall cost and development time. As a result, a growing number of computational drug repositioning methods have emerged. Heterogeneous network-based drug repositioning methods have been shown to outperform other approaches. However, there is a dearth of systematic evaluation studies of these methods, encompassing performance, scalability and usability, as well as a standardized process for evaluating new methods. Additionally, previous studies have only compared several methods, with conflicting results. In this context, we conducted a systematic benchmarking study of 28 heterogeneous network-based drug repositioning methods on 11 existing datasets. We developed a comprehensive framework to evaluate their performance, scalability and usability. Our study revealed that methods such as HGIMC, ITRPCA and BNNR exhibit the best overall performance, as they rely on matrix completion or factorization. HINGRL, MLMC, ITRPCA and HGIMC demonstrate the best performance, while NMFDR, GROBMC and SCPMF display superior scalability. For usability, HGIMC, DRHGCN and BNNR are the top performers. Building on these findings, we developed an online tool called HN-DREP (http://hn-drep.lyhbio.com/) to facilitate researchers in viewing all the detailed evaluation results and selecting the appropriate method. HN-DREP also provides an external drug repositioning prediction service for a specific disease or drug by integrating predictions from all methods. Furthermore, we have released a Snakemake workflow named HN-DRES (https://github.com/lyhbio/HN-DRES) to facilitate benchmarking and support the extension of new methods into the field.

Matrix reconstruction with reliable neighbors for predicting potential MiRNA-disease associations.

Numerous experimental studies have indicated that alteration and dysregulation in mircroRNAs (miRNAs) are associated with serious diseases. Identifying disease-related miRNAs is therefore an essential and challenging task in bioinformatics research. Computational methods are an efficient and economical alternative to conventional biomedical studies and can reveal underlying miRNA-disease associations for subsequent experimental confirmation with reasonable confidence. Despite the success of existing computational approaches, most of them only rely on the known miRNA-disease associations to predict associations without adding other data to increase the prediction accuracy, and they are affected by issues of data sparsity. In this paper, we present MRRN, a model that combines matrix reconstruction with node reliability to predict probable miRNA-disease associations. In MRRN, the most reliable neighbors of miRNA and disease are used to update the original miRNA-disease association matrix, which significantly reduces data sparsity. Unknown miRNA-disease associations are reconstructed by aggregating the most reliable first-order neighbors to increase prediction accuracy by representing the local and global structure of the heterogeneous network. Five-fold cross-validation of MRRN produced an area under the curve (AUC) of 0.9355 and area under the precision-recall curve (AUPR) of 0.2646, values that were greater than those produced by comparable models. Two different types of case studies using three diseases were conducted to demonstrate the accuracy of MRRN, and all top 30 predicted miRNAs were verified.

Novel Modification of Integrated Optimization Method for Sensor's Communication in Wi-Fi Public Networks.

A novel modification of IP networks integrated optimization method for heterogeneous networks, for example, the seamless Wi-Fi network serving simultaneously mobile users and wireless sensors, has been developed in this article. The mutual influence of signal reception, frequency-territorial planning, and routing procedures in heterogeneous networks have been analyzed in the case of simultaneous data transmission by both mobile users and wireless sensors. New principles for the listed procedures interaction and the basic functions for their describing are formulated. A novel modification of the integrated optimization method and its algorithm have been developed. The developed method's effectiveness has been analyzed for the IEEE 802.11ax network segment. Its result showed that the network load was decreased by an average of 20%, the data rate over the network as a whole increased for users and sensors by an average of 25% and 40%, respectively, and the sensors' lifetime increased by an average of 20% compared to the novel modification of the Collective Dynamic Routing method.

Cytoscape stringApp 2.0: Analysis and Visualization of Heterogeneous Biological Networks.

Biological networks are often used to represent complex biological systems, which can contain several types of entities. Analysis and visualization of such networks is supported by the Cytoscape software tool and its many apps. While earlier versions of stringApp focused on providing intraspecies protein-protein interactions from the STRING database, the new stringApp 2.0 greatly improves the support for heterogeneous networks. Here, we highlight new functionality that makes it possible to create networks that contain proteins and interactions from STRING as well as other biological entities and associations from other sources. We exemplify this by complementing a published SARS-CoV-2 interactome with interactions from STRING. We have also extended stringApp with new data and query functionality for protein-protein interactions between eukaryotic parasites and their hosts. We show how this can be used to retrieve and visualize a cross-species network for a malaria parasite, its host, and its vector. Finally, the latest stringApp version has an improved user interface, allows retrieval of both functional associations and physical interactions, and supports group-wise enrichment analysis of different parts of a network to aid biological interpretation. stringApp is freely available at https://apps.cytoscape.org/apps/stringapp.

Competitive dual-strain SIS epidemiological models with awareness programs in heterogeneous networks: two modeling approaches.

Epidemic diseases and media campaigns are closely associated with each other. Considering most epidemics have multiple pathogenic strains, in this paper, we take the lead in proposing two multi-strain SIS epidemic models in heterogeneous networks incorporating awareness programs due to media. For the first model, we assume that the transmission rates for strain 1 and strain 2 depend on the level of awareness campaigns. For the second one, we further suppose that awareness divides susceptible population into two different subclasses. After defining the basic reproductive numbers for the whole model and each strain, we obtain the analytical conditions that determine the extinction, coexistence and absolute dominance of two strains. Moreover, we also formulate its optimal control problem and identify an optimal implementation pair of awareness campaigns using optimal control theory. Given the complexity of the second model, we use the numerical simulations to visualize its different types of dynamical behaviors. Through theoretical and numerical analysis of these two models, we discover some new phenomena. For example, during the persistence analysis of the first model, we find that the characteristic polynomials of two boundary equilibria may have a pair of pure imaginary roots, implying that Hopf bifurcation and periodic solutions may appear. Most strikingly, multistability occurs in the second model and the growth rate of awareness programs (triggered by the infection prevalence) has a multistage impact on the final size of two strains. The numerical results suggest that the spread of a two-strain epidemic can be controlled (even be eradicated) by taking the measures of enhancing awareness transmission, reducing memory fading of aware individuals and ensuring high-level influx and rapid growth of awareness programs appropriately.

Contract-Optimization Approach (COA): A New Approach for Optimizing Service Caching, Computation Offloading, and Resource Allocation in Mobile Edge Computing Network.

An optimal method for resource allocation based on contract theory is proposed to improve energy utilization. In heterogeneous networks (HetNets), distributed heterogeneous network architectures are designed to balance different computing capacities, and MEC server gains are designed based on the amount of allocated computing tasks. An optimal function based on contract theory is developed to optimize the revenue gain of MEC servers while considering constraints such as service caching, computation offloading, and the number of resources allocated. As the objective function is a complex problem, it is solved utilizing equivalent transformations and variations of the reduced constraints. A greedy algorithm is applied to solve the optimal function. A comparative experiment on resource allocation is conducted, and energy utilization parameters are calculated to compare the effectiveness of the proposed algorithm and the main algorithm. The results show that the proposed incentive mechanism has a significant advantage in improving the utility of the MEC server.

Enhancing Data Freshness in Air-Ground Collaborative Heterogeneous Networks through Contract Theory and Generative Diffusion-Based Mobile Edge Computing.

Mobile edge computing is critical for improving the user experience of latency-sensitive and freshness-based applications. This paper provides insights into the potential of non-orthogonal multiple access (NOMA) convergence with heterogeneous air-ground collaborative networks to improve system throughput and spectral efficiency. Coordinated resource allocation between UAVs and MEC servers, especially in the NOMA framework, is addressed as a key challenge. Under the unrealistic assumption that edge nodes contribute resources indiscriminately, we introduce a two-stage incentive mechanism. The model is based on contract theory and aims at optimizing the utility of the service provider (SP) under the constraints of individual rationality (IR) and incentive compatibility (IC) of the mobile user. The block coordinate descent method is used to refine the contract design and complemented by a generative diffusion model to improve the efficiency of searching for contracts. During the deployment process, the study emphasizes the positioning of UAVs to maximize SP effectiveness. An improved differential evolutionary algorithm is introduced to optimize the positioning of UAVs. Extensive evaluation shows our approach has excellent effectiveness and robustness in deterministic and unpredictable scenarios.

A Survey on Handover and Mobility Management in 5G HetNets: Current State, Challenges, and Future Directions.

Fifth-generation (5G) networks offer high-speed data transmission with low latency, increased base station volume, improved quality of service (QoS), and massive multiple-input-multiple-output (M-MIMO) channels compared to 4G long-term evolution (LTE) networks. However, the COVID-19 pandemic has disrupted the achievement of mobility and handover (HO) in 5G networks due to significant changes in intelligent devices and high-definition (HD) multimedia applications. Consequently, the current cellular network faces challenges in propagating high-capacity data with improved speed, QoS, latency, and efficient HO and mobility management. This comprehensive survey paper specifically focuses on HO and mobility management issues within 5G heterogeneous networks (HetNets). The paper thoroughly examines the existing literature and investigates key performance indicators (KPIs) and solutions for HO and mobility-related challenges while considering applied standards. Additionally, it evaluates the performance of current models in addressing HO and mobility management issues, taking into account factors such as energy efficiency, reliability, latency, and scalability. Finally, this paper identifies significant challenges associated with HO and mobility management in existing research models and provides detailed evaluations of their solutions along with recommendations for future research.

Joint Detection and Communication over Type-Sensitive Networks.

Due to the difficulty of decentralized inference with conditional dependent observations, and motivated by large-scale heterogeneous networks, we formulate a framework for decentralized detection with coupled observations. Each agent has a state, and the empirical distribution of all agents' states or the type of network dictates the individual agents' behavior. In particular, agents' observations depend on both the underlying hypothesis as well as the empirical distribution of the agents' states. Hence, our framework captures a high degree of coupling, in that an individual agent's behavior depends on both the underlying hypothesis and the behavior of all other agents in the network. Considering this framework, the method of types, and a series of equicontinuity arguments, we derive the error exponent for the case in which all agents are identical and show that this error exponent depends on only a single empirical distribution. The analysis is extended to the multi-class case, and numerical results with state-dependent agent signaling and state-dependent channels highlight the utility of the proposed framework for analysis of highly coupled environments.

Self-segregation in heterogeneous metapopulation landscapes.

Complex interactions are at the root of the population dynamics of many natural systems, particularly for being responsible for the allocation of species and individuals across apposite niches of the ecological landscapes. On the other side, the randomness that unavoidably characterises complex systems has increasingly challenged the niche paradigm providing alternative neutral theoretical models. We introduce a network-inspired metapopulation individual-based model (IBM), hereby named self-segregation, where the density of individuals in the hosting patches (local habitats) drives the individuals spatial assembling while still constrained by nodes' saturation. In particular, we prove that the core-periphery structure of the networked landscape triggers the spontaneous emergence of vacant habitat patches, which segregate the population in multistable patterns of isolated (sub)communities separated by empty patches. Furthermore, a quantisation effect in the number of vacant patches is observed once the total system mass varies continuously, emphasising thus a striking feature of the robustness of population stationary distributions. Notably, our model reproduces the patch vacancy found in the fragmented habitat of the Glanville fritillary butterfly Melitaea cinxia, an endemic species of the Åland islands. We argue that such spontaneous breaking of the natural habitat supports the concept of the highly contentious (Grinnellian) niche vacancy and also suggests a new mechanism for the endogeneous habitat fragmentation and consequently the peripatric speciation.

Stochastic synchronization in nonlinear network systems driven by intrinsic and coupling noise.

In this paper, we consider a noisy network of nonlinear systems in the sense that each system is driven by two sources of state-dependent noise: (1) an intrinsic noise that can be generated by the environment or any internal fluctuations and (2) a noisy coupling which is generated by interactions with other systems. Our goal is to understand the effect of noise and coupling on synchronization behaviors of such networks. First, we assume that all the systems are driven by a common noise and show how a common noise can be detrimental or beneficial for network synchronization behavior. Then, we assume that the systems are driven by independent noise and study network approximate synchronization behavior. We numerically illustrate our results using the example of coupled Van der Pol oscillators.

Wireless Link Selection Methods for Maritime Communication Access Networks-A Deep Learning Approach.

In recent years, we have been witnessing a growing interest in the subject of communication at sea. One of the promising solutions to enable widespread access to data transmission capabilities in coastal waters is the possibility of employing an on-shore wireless access infrastructure. However, such an infrastructure is a heterogeneous one, managed by many independent operators and utilizing a number of different communication technologies. If a moving sea vessel is to maintain a reliable communication within such a system, it needs to employ a set of network mechanisms dedicated for this purpose. In this paper, we provide a short overview of such requirements and overall characteristics of maritime communication, but our main focus is on the link selection procedure-an element of critical importance for the process of changing the device/system which the mobile vessel uses to retain communication with on-shore networks. The paper presents the concept of employing deep neural networks for the purpose of link selection. The proposed methods have been verified using propagation models dedicated to realistically represent the environment of maritime communications and compared to a number of currently popular solutions. The results of evaluation indicate a significant gain in both accuracy of predictions and reduction of the amount of test traffic which needs to be generated for measurements.

QoS-Aware Resource Allocation with Pilot-Aided Channel Estimation for Heterogeneous Wireless Networks.

The deployment of heterogeneous networks (HetNets) is a way to increase the network capacity and release part of the traffic generated by users inside a cell to small-scale wireless networks for service. In this context, the main problem is managing the interference due to the coexistence of small cells and macro cells. In this paper, a QoS-aware Resource Allocation (RA) algorithm jointly working with admission control (AC) over a two-tier HetNet scenario is investigated in the presence of both the pilot-symbols for channel estimation and the channel estimation error. The RA algorithm allows two users, the macro cell user (CU) and small cell user (SU), to simultaneously share the same resource block. Moreover, system performance and fairness are improved by including adaptive power allocation to users over resource blocks. In the framework of RA with proportional rate constraints, a novel algorithm is designed by including the effects of pilot-aided channel estimation. The algorithm is able to distribute the same proportional rate to all CUs and SUs, even in the presence of channel estimation error. Relevant numerical results for the downlink of a two-tier HetNet with pilot-aided channel estimation show that the rate dispersion is driven to zero while the sum-rate is maximized, and the average user rate penalty with respect to a perfect-CSI scenario may rise to 20%.

A Dynamic Algorithm for Interference Management in D2D-Enabled Heterogeneous Cellular Networks: Modeling and Analysis.

To supporting a wider and diverse range of applications, device-to-device (D2D) communication is a key enabler in heterogeneous cellular networks (HetCNets). It plays an important role in fulfilling the performance and quality of service (QoS) requirements for 5G networks and beyond. D2D-enabled cellular networks enable user equipment (UE) to communicate directly, without any or with a partial association with base stations (eNBs). Interference management is one of the critical and complex issues in D2D-enabled HetCNets. Despite the wide adoption of D2D communications, there are very few researchers addressing the problems of mode selection (MS), as well as resource allocation for mutual interference in three-tier cellular networks. In this paper, we first identify and analyze three key factors, namely outage probability, signal-to-interference and noise ratio (SINR), and cell density that influence the performance of D2D-enabled HetCNets. We then propose a dynamic algorithm based on a distance-based approach to minimize the interference and to guarantee QoS for both cellular and D2D communication links. Results obtained show that outage probability is improved by 35% and 49% in eNB and SCeNB links, respectively, when compared with traditional neighbor-based methods. The findings reported in this paper provide some insights into interference management in D2D communications that can help network researchers and engineers contribute to further developing next-generation cellular networks.

Deep Reinforcement Learning Based Optical and Acoustic Dual Channel Multiple Access in Heterogeneous Underwater Sensor Networks.

In this paper, we investigate how to efficiently utilize channel bandwidth in heterogeneous hybrid optical and acoustic underwater sensor networks, where sensor nodes adopt different Media Access Control (MAC) protocols to transmit data packets to a common relay node on optical or acoustic channels. We propose a new MAC protocol based on deep reinforcement learning (DRL), referred to as optical and acoustic dual-channel deep-reinforcement learning multiple access (OA-DLMA), in which the sensor nodes utilizing the OA-DLMA protocol are called agents, and the remainder are non-agents. The agents can learn the transmission patterns of coexisting non-agents and find an optimal channel access strategy without any prior information. Moreover, in order to further enhance network performance, we develop a differentiated reward policy that rewards specific actions over optical and acoustic channels differently, with priority compensation being given to the optical channel to achieve greater data transmission. Furthermore, we have derived the optimal short-term sum throughput and channel utilization analytically and conducted extensive simulations to evaluate the OA-DLMA protocol. Simulation results show that our protocol performs with near-optimal performance and significantly outperforms other existing protocols in terms of short-term sum throughput and channel utilization.

Graph-Based Resource Allocation for Integrated Space and Terrestrial Communications.

Resource allocation (RA) has always had a prominent place in wireless communications research due to its significance for network throughput maximization, and its inherent complexity. Concurrently, graph-based solutions for RA have also grown in importance, providing opportunities for higher throughput and efficiency due to their representational capabilities, as well as challenges for realizing scalable algorithms. This article presents a comprehensive review and analysis of graph-based RA methods in three major wireless network types: cellular homogeneous and heterogeneous, device-to-device, and cognitive radio networks. The main design characteristics, as well as directions for future research, are provided for each of these categories. On the basis of this review, the concept of Graph-based Resource allocation for Integrated Space and Terrestrial communications (GRIST) is proposed. It describes the inter-connectivity and coexistence of various terrestrial and non-terrestrial networks via a hypergraph and its attributes. In addition, the implementation challenges of GRIST are explained in detail. Finally, to complement GRIST, a scheme for determining the appropriate balance between different design considerations is introduced. It is described via a simplified complete graph-based design process for resource management algorithms.

A Deep Q-Network-Based Algorithm for Multi-Connectivity Optimization in Heterogeneous Cellular-Networks.

The use of multi-connectivity has become a useful tool to manage the traffic in heterogeneous cellular network deployments, since it allows a device to be simultaneously connected to multiple cells. The proper exploitation of this technique requires to adequately configure the traffic sent through each cell depending on the experienced conditions. This motivates this work, which tackles the problem of how to optimally split the traffic among the cells when the multi-connectivity feature is used. To this end, the paper proposes the use of a deep reinforcement learning solution based on a Deep Q-Network (DQN) in order to determine the amount of traffic of a device that needs to be delivered through each cell, making the decision as a function of the current traffic and radio conditions. The obtained results show a near-optimal performance of the DQN-based solution with an average difference of only 3.9% in terms of reward with respect to the optimum strategy. Moreover, the solution clearly outperforms a reference scheme based on Signal to Interference Noise Ratio (SINR) with differences of up to 50% in terms of reward and up to 166% in terms of throughput for certain situations. Overall, the presented results show the promising performance of the DQN-based approach that establishes a basis for further research in the topic of multi-connectivity and for the application of this type of techniques in other problems of the radio access network.

Network-Based Approaches for Disease-Gene Association Prediction Using Protein-Protein Interaction Networks.

Genome-wide association studies (GWAS) can be used to infer genome intervals that are involved in genetic diseases. However, investigating a large number of putative mutations for GWAS is resource- and time-intensive. Network-based computational approaches are being used for efficient disease-gene association prediction. Network-based methods are based on the underlying assumption that the genes causing the same diseases are located close to each other in a molecular network, such as a protein-protein interaction (PPI) network. In this survey, we provide an overview of network-based disease-gene association prediction methods based on three categories: graph-theoretic algorithms, machine learning algorithms, and an integration of these two. We experimented with six selected methods to compare their prediction performance using a heterogeneous network constructed by combining a genome-wide weighted PPI network, an ontology-based disease network, and disease-gene associations. The experiment was conducted in two different settings according to the presence and absence of known disease-associated genes. The results revealed that HerGePred, an integrative method, outperformed in the presence of known disease-associated genes, whereas PRINCE, which adopted a network propagation algorithm, was the most competitive in the absence of known disease-associated genes. Overall, the results demonstrated that the integrative methods performed better than the methods using graph-theory only, and the methods using a heterogeneous network performed better than those using a homogeneous PPI network only.

Integration of Neighbor Topologies Based on Meta-Paths and Node Attributes for Predicting Drug-Related Diseases.

Identifying new disease indications for existing drugs can help facilitate drug development and reduce development cost. The previous drug-disease association prediction methods focused on data about drugs and diseases from multiple sources. However, they did not deeply integrate the neighbor topological information of drug and disease nodes from various meta-path perspectives. We propose a prediction method called NAPred to encode and integrate meta-path-level neighbor topologies, multiple kinds of drug attributes, and drug-related and disease-related similarities and associations. The multiple kinds of similarities between drugs reflect the degrees of similarity between two drugs from different perspectives. Therefore, we constructed three drug-disease heterogeneous networks according to these drug similarities, respectively. A learning framework based on fully connected neural networks and a convolutional neural network with an attention mechanism is proposed to learn information of the neighbor nodes of a pair of drug and disease nodes. The multiple neighbor sets composed of different kinds of nodes were formed respectively based on meta-paths with different semantics and different scales. We established the attention mechanisms at the neighbor-scale level and at the neighbor topology level to learn enhanced neighbor feature representations and enhanced neighbor topological representations. A convolutional-autoencoder-based module is proposed to encode the attributes of the drug-disease pair in three heterogeneous networks. Extensive experimental results indicated that NAPred outperformed several state-of-the-art methods for drug-disease association prediction, and the improved recall rates demonstrated that NAPred was able to retrieve more actual drug-disease associations from the top-ranked candidates. Case studies on five drugs further demonstrated the ability of NAPred to identify potential drug-related disease candidates.

Dynamic Analysis and Optimal Control of Rumor Spreading Model with Recurrence and Individual Behaviors in Heterogeneous Networks.

This paper is devoted to investigating the impact of the recurrence of rumors and individual behaviors and control strategies related to rumor spreading in online social networks. To do this, a novel susceptible-hesitating-infected-latent-recovered (SHILR) rumor propagation model in heterogeneous networks is presented. Firstly, based on the relevant mean-field equations of the model, the threshold value is examined to demonstrate the existence and stability of rumor-free/spreading equilibrium with the help of the algebraic method. Secondly, the global stabilities of the equilibria are analyzed through applying Lyapunov stability theory and LaSalle's invariance principle. Next, the optimal control is proposed by taking advantage of Pontryagin's maximum principle for reducing the number of infected individuals with minimum cost. Moreover, some numerical examples are carried out to test the theoretical results. Finally, combined with practice, a model application is presented.