Heuristic Approaches for Enhancing the Privacy of the Leader in IoT Networks.

The privacy and security of the Internet of Things (IoT) are emerging as popular issues in the IoT. At present, there exist several pieces of research on network analysis on the IoT network, and malicious network analysis may threaten the privacy and security of the leader in the IoT networks. With this in mind, we focus on how to avoid malicious network analysis by modifying the topology of the IoT network and we choose closeness centrality as the network analysis tool. This paper makes three key contributions toward this problem: (1) An optimization problem of removing k edges to minimize (maximize) the closeness value (rank) of the leader; (2) A greedy (greedy and simulated annealing) algorithm to solve the closeness value (rank) case of the proposed optimization problem in polynomial time; and (3)UpdateCloseness (FastTopRank)-algorithm for computing closeness value (rank) efficiently. Experimental results prove the efficiency of our pruning algorithms and show that our heuristic algorithms can obtain accurate solutions compared with the optimal solution (the approximation ratio in the worst case is 0.85) and outperform the solutions obtained by other baseline algorithms (e.g., choose k edges with the highest degree sum).

Distance Entropy Cartography Characterises Centrality in Complex Networks.

We introduce distance entropy as a measure of homogeneity in the distribution of path lengths between a given node and its neighbours in a complex network. Distance entropy defines a new centrality measure whose properties are investigated for a variety of synthetic network models. By coupling distance entropy information with closeness centrality, we introduce a network cartography which allows one to reduce the degeneracy of ranking based on closeness alone. We apply this methodology to the empirical multiplex lexical network encoding the linguistic relationships known to English speaking toddlers. We show that the distance entropy cartography better predicts how children learn words compared to closeness centrality. Our results highlight the importance of distance entropy for gaining insights from distance patterns in complex networks.

Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer's Disease.

Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology.

A biologically inspired immunization strategy for network epidemiology.

Well-known immunization strategies, based on degree centrality, betweenness centrality, or closeness centrality, either neglect the structural significance of a node or require global information about the network. We propose a biologically inspired immunization strategy that circumvents both of these problems by considering the number of links of a focal node and the way the neighbors are connected among themselves. The strategy thus measures the dependence of the neighbors on the focal node, identifying the ability of this node to spread the disease. Nodes with the highest ability in the network are the first to be immunized. To test the performance of our method, we conduct numerical simulations on several computer-generated and empirical networks, using the susceptible-infected-recovered (SIR) model. The results show that the proposed strategy largely outperforms the existing well-known strategies.

EEG-based spatiotemporal dynamics of fast ripple networks and hubs in infantile epileptic spasms.

OBJECTIVE: Infantile epileptic spasms (IS) are epileptic seizures that are associated with increased risk for developmental impairments, adult epilepsies, and mortality. Here, we investigated coherence-based network dynamics in scalp EEG of infants with IS to identify frequency-dependent networks associated with spasms. We hypothesized that there is a network of increased fast ripple connectivity during the electrographic onset of clinical spasms, which is distinct from controls. METHODS: We retrospectively analyzed peri-ictal and interictal EEG recordings of 14 IS patients. The data was compared with 9 age-matched controls. Wavelet phase coherence (WPC) was computed between 0.2 and 400 Hz. Frequency- and time-dependent brain networks were constructed using this coherence as the strength of connection between two EEG channels, based on graph theory principles. Connectivity was evaluated through global efficiency (GE) and channel-based closeness centrality (CC), over frequency and time. RESULTS: GE in the fast ripple band (251-400 Hz) was significantly greater following the onset of spasms in all patients (P < 0.05). Fast ripple networks during the first 10s from spasm onset show enhanced anteroposterior gradient in connectivity (posterior > central > anterior, Kruskal-Wallis P < 0.001), with maximum CC over the centroparietal channels in 10/14 patients. Additionally, this anteroposterior gradient in CC connectivity is observed during spasms but not during the interictal awake or asleep states of infants with IS. In controls, anteroposterior gradient in fast ripple CC was noted during arousals and wakefulness but not during sleep. There was also a simultaneous decrease in GE in the 5-8 Hz range after the onset of spasms (P < 0.05), of unclear biological significance. SIGNIFICANCE: We identified an anteroposterior gradient in the CC connectivity of fast ripple hubs during spasms. This anteroposterior gradient observed during spasms is similar to the anteroposterior gradient in the CC connectivity observed in wakefulness or arousals in controls, suggesting that this state change is related to arousal networks.

The autism spectrum disorder risk gene NEXMIF over-synchronizes hippocampal CA1 network and alters neuronal coding.

Mutations in autism spectrum disorder (ASD) risk genes disrupt neural network dynamics that ultimately lead to abnormal behavior. To understand how ASD-risk genes influence neural circuit computation during behavior, we analyzed the hippocampal network by performing large-scale cellular calcium imaging from hundreds of individual CA1 neurons simultaneously in transgenic mice with total knockout of the X-linked ASD-risk gene NEXMIF (neurite extension and migration factor). As NEXMIF knockout in mice led to profound learning and memory deficits, we examined the CA1 network during voluntary locomotion, a fundamental component of spatial memory. We found that NEXMIF knockout does not alter the overall excitability of individual neurons but exaggerates movement-related neuronal responses. To quantify network functional connectivity changes, we applied closeness centrality analysis from graph theory to our large-scale calcium imaging datasets, in addition to using the conventional pairwise correlation analysis. Closeness centrality analysis considers both the number of connections and the connection strength between neurons within a network. We found that in wild-type mice the CA1 network desynchronizes during locomotion, consistent with increased network information coding during active behavior. Upon NEXMIF knockout, CA1 network is over-synchronized regardless of behavioral state and fails to desynchronize during locomotion, highlighting how perturbations in ASD-implicated genes create abnormal network synchronization that could contribute to ASD-related behaviors.

Cognitive network reconstruction in individuals who use opioids compared to those who do not: Topological analysis of cognitive function through graph model and centrality measures.

Introduction: Cognitive dysfunction related to opioid use disorder (OUD) requires investigation of the interconnected network of cognitive domains through behavioral experiments and graph data modeling. Methods: We conducted n-back, selective and divided attention, and Wisconsin card sorting tests and reconstructed the interactive cognitive network of subscales or domains for individuals who use opioids and controls to identify the most central cognitive functions and their connections using graph model analysis. Each two subscales with significant correlations were connected by an edge that incorporated in formation of interactive networks. Each network was analyzed topologically based on the betweenness and closeness centrality measures. Results: Results from the network reconstructed for individuals who use opioids show that in the divided attention module, reaction time and number of commission errors were the most central subscales of cognitive function. Whereas in controls, the number of correct responses and commission errors were the most central cognitive measure. We found that the subscale measures of divided attention module are significantly correlated with those of other tests. These findings corroborate that persons who use opioids show impaired divided attention as higher reaction time and errors in performing tasks. Divided attention is the most central cognitive function in both OUD subjects and controls, although differences were observed between the two groups in various subscales. Discussion: Although equal proportions of males and females may be used in future studies, divided attention and its subscales may be the most promising target for cognitive therapies, treatments and rehabilitation as their improvement can enhance overall cognitive domain performance.

Road networks structure analysis: A preliminary network science-based approach.

Road network studies attracted unprecedented and overwhelming interest in recent years due to the clear relationship between human existence and city evolution. Current studies cover many aspects of a road network, for example, road feature extraction from video/image data, road map generalisation, traffic simulation, optimisation of optimal route finding problems, and traffic state prediction. However, analysing road networks as a complex graph is a field to explore. This study presents comparative studies on the Porto, in Portugal, road network sections, mainly of Matosinhos, Paranhos, and Maia municipalities, regarding degree distributions, clustering coefficients, centrality measures, connected components, k-nearest neighbours, and shortest paths. Further insights into the networks took into account the community structures, page rank, and small-world analysis. The results show that the information exchange efficiency of Matosinhos is 0.8, which is 10 and 12.8% more significant than that of the Maia and Paranhos networks, respectively. Other findings stated are: (1) the studied road networks are very accessible and densely linked; (2) they are small-world in nature, with an average length of the shortest pathways between any two roads of 29.17 units, which as found in the scenario of the Maia road network; and (3) the most critical intersections of the studied network are 'Avenida da Boavista, 4100-119 Porto (latitude: 41.157944, longitude: - 8.629105)', and 'Autoestrada do Norte, Porto (latitude: 41.1687869, longitude: - 8.6400656)', based on the analysis of centrality measures.

Novel dynamic residue network analysis approaches to study allosteric modulation: SARS-CoV-2 Mpro and its evolutionary mutations as a case study.

The rational search for allosteric modulators and the allosteric mechanisms of these modulators in the presence of mutations is a relatively unexplored field. Here, we established novel in silico approaches and applied them to SARS-CoV-2 main protease (Mpro) as a case study. First, we identified six potential allosteric modulators. Then, we focused on understanding the allosteric effects of these modulators on each of its protomers. We introduced a new combinatorial approach and dynamic residue network (DRN) analysis algorithms to examine patterns of change and conservation of critical nodes, according to five independent criteria of network centrality. We observed highly conserved network hubs for each averaged DRN metric on the basis of their existence in both protomers in the absence and presence of all ligands (persistent hubs). We also detected ligand specific signal changes. Using eigencentrality (EC) persistent hubs and ligand introduced hubs we identified a residue communication path connecting the allosteric binding site to the catalytic site. Finally, we examined the effects of the mutations on the behavior of the protein in the presence of selected potential allosteric modulators and investigated the ligand stability. One crucial outcome was to show that EC centrality hubs form an allosteric communication path between the allosteric ligand binding site to the active site going through the interface residues of domains I and II; and this path was either weakened or lost in the presence of some of the mutations. Overall, the results revealed crucial aspects that need to be considered in rational computational drug discovery.

Network centrality analysis of eye-gaze data in autism spectrum disorder.

Individuals suffering from autism spectrum disorder (ASD) exhibit impaired social communication, the manifestations of which include abnormal eye contact and gaze. In this study, we first seek to characterize the spatial and temporal attributes of this atypical eye gaze. To achieve that goal, we analyze and compare eye-tracking data of ASD and typical development (TD) children. A fixation time analysis indicates that ASD children exhibit a distinct gaze pattern when looking at faces, spending significantly more time at the mouth and less at the eyes, compared with TD children. Another goal of this study is to identify an analytic approach that can better reveal differences between the face scanning patterns of ASD and TD children. Face scanning involves transitioning from one area of interest (AOI) to another and is not taken into account by the traditional fixation time analysis. Instead, we apply four network analysis approaches that measure the "importance" of a given AOI: degree centrality, betweenness centrality, closeness centrality, and eigenvector centrality. Degree centrality and eignevector centrality yield statistically significant difference in the mouth and right eye, respectively, between the ASD and TD groups, whereas betweenness centrality reveals statistically significant between-group differences in four AOIs. Closeness centrality yields statistically meaningful differences in three AOIs, but those differences are negligible. Thus, our results suggest that betweenness centrality is the most effective network analysis approach in distinguishing the eye gaze patterns between ASD and TD children.

Applying graphs and complex networks to football metric interpretation.

This work presents a methodology for analysing the interactions between players in a football team, from the point of view of graph theory and complex networks. We model the complex network of passing interactions between players of a same team in 32 official matches of the Liga de Fútbol Profesional (Spain), using a passing/reception graph. This methodology allows us to understand the play structure of the team, by analysing the offensive phases of game-play. We utilise two different strategies for characterising the contribution of the players to the team: the clustering coefficient, and centrality metrics (closeness and betweenness). We show the application of this methodology by analyzing the performance of a professional Spanish team according to these metrics and the distribution of passing/reception in the field. Keeping in mind the dynamic nature of collective sports, in the future we will incorporate metrics which allows us to analyse the performance of the team also according to the circumstances of game-play and to different contextual variables such as, the utilisation of the field space, the time, and the ball, according to specific tactical situations.

Exploring allosteric communication in multiple states of the bacterial ribosome using residue network analysis.

Antibiotic resistance is one of the most important problems of our era and hence the discovery of new effective therapeutics is urgent. At this point, studying the allosteric communication pathways in the bacterial ribosome and revealing allosteric sites/residues is critical for designing new inhibitors or repurposing readily approved drugs for this enormous machine. To shed light onto molecular details of the allosteric mechanisms, here we construct residue networks of the bacterial ribosomal complex at four different states of translation by using an effective description of the intermolecular interactions. Centrality analysis of these networks highlights the functional roles of structural components and critical residues on the ribosomal complex. High betweenness scores reveal pathways of residues connecting numerous sites on the structure. Interestingly, these pathways assemble highly conserved residues, drug binding sites, and known allosterically linked regions on the same structure. This study proposes a new residue-level model to test how distant sites on the molecular machine may be linked through hub residues that are critically located on the contact topology to inherently form communication pathways. Findings also indicate intersubunit bridges B1b, B3, B5, B7, and B8 as critical targets to design novel antibiotics.

Hierarchical core decomposition of RING structure as a method to capture novel functional residues within RING-type E3 ligases: a structural systems biology approach.

BACKGROUND: Increasing amounts of evidence strongly suggest that mutations located in RING (Really Interesting New Gene) domains of E3 ligases are involved in cancer development. Despite the existence of many experimentally defined E3 RING structures, there are still many RING mutations in the Catalog of Somatic Mutations in Cancer (COSMIC), with an unknown structural or functional significance, which are usually substitutions of amino acids with no conservation at the corresponding position. The core decomposition of networks has long been used in systems biology but never utilized in protein structure networks to identify a tolerant "core" to peripheral structure changes or failures, a region that is usually not easy to be determined with high accuracy through classical 3D protein structure analyses. METHOD: A new structure decomposition method that utilizes network analysis and computational thermodynamic measures of fold stability changes upon amino acids alterations is proposed. RESULTS: In particular, by successively pruning the entire RING structure network of three cancer-associated E3s (BRCA1, MDM2, and cIAP2), a ''core'' for each RING domain is left. Interestingly, substitutions of ''core'' residues are associated with cancers according to COSMIC catalog. Unexpectedly, 80% of the residues located in the ''core'' RING subnetworks are non-conserved within E3 RING domains. To validate the predictions, the function of the identified RING ''core'' amino acids as well as the effects of their substitutions on E3 Ub ligase activity were mined from the literature and investigated by computational tools and in vitro Ub ligase assays. CONCLUSIONS: This method could be widely applicable as a source of novel functional RING residues, non-conserved in E3s, for which substitutions could be deleterious.

Influence spreading model used to analyse social networks and detect sub-communities.

A dynamic influence spreading model is presented for computing network centrality and betweenness measures. Network topology, and possible directed connections and unequal weights of nodes and links, are essential features of the model. The same influence spreading model is used for community detection in social networks and for analysis of network structures. Weaker connections give rise to more sub-communities whereas stronger ties increase the cohesion of a community. The validity of the method is demonstrated with different social networks. Our model takes into account different paths between nodes in the network structure. The dependency of different paths having common links at the beginning of their paths makes the model more realistic compared to classical structural, simulation and random walk models. The influence of all nodes in a network has not been satisfactorily understood. Existing models may underestimate the spreading power of interconnected peripheral nodes as initiators of dynamic processes in social, biological and technical networks.

The Influence of Closeness Centrality on Lexical Processing.

The present study examined how the network science measure known as closeness centrality (which measures the average distance between a node and all other nodes in the network) influences lexical processing. In the mental lexicon, a word such as CAN has high closeness centrality, because it is close to many other words in the lexicon. Whereas, a word such as CURE has low closeness centrality because it is far from other words in the lexicon. In an auditory lexical decision task (Experiment 1) participants responded more quickly to words with high closeness centrality. In Experiment 2 an auditory lexical decision task was again used, but with a wider range of stimulus characteristics. Although, there was no main effect of closeness centrality in Experiment 2, an interaction between closeness centrality and frequency of occurrence was observed on reaction times. The results are explained in terms of partial activation gradually strengthening over time word-forms that are centrally located in the phonological network.

PINTnet: construction of condition-specific pathway interaction network by computing shortest paths on weighted PPI.

BACKGROUND: Identifying perturbed pathways in a given condition is crucial in understanding biological phenomena. In addition to identifying perturbed pathways individually, pathway analysis should consider interactions among pathways. Currently available pathway interaction prediction methods are based on the existence of overlapping genes between pathways, protein-protein interaction (PPI) or functional similarities. However, these approaches just consider the pathways as a set of genes, thus they do not take account of topological features. In addition, most of the existing approaches do not handle the explicit gene expression quantity information that is routinely measured by RNA-sequecing. RESULTS: To overcome these technical issues, we developed a new pathway interaction network construction method using PPI, closeness centrality and shortest paths. We tested our approach on three different high-throughput RNA-seq data sets: pregnant mice data to reveal the role of serotonin on beta cell mass, bone-metastatic breast cancer data and autoimmune thyroiditis data to study the role of IFN- α. Our approach successfully identified the pathways reported in the original papers. For the pathways that are not directly mentioned in the original papers, we were able to find evidences of pathway interactions by the literature search. Our method outperformed two existing approaches, overlapping gene-based approach (OGB) and protein-protein interaction-based approach (PB), in experiments with the three data sets. CONCLUSION: Our results show that PINTnet successfully identified condition-specific perturbed pathways and the interactions between the pathways. We believe that our method will be very useful in characterizing biological mechanisms at the pathway level. PINTnet is available at http://biohealth.snu.ac.kr/software/PINTnet/ .

Graph analysis of ß2 adrenergic receptor structures: a "social network" of GPCR residues.

PURPOSE: G protein-coupled receptors (GPCRs) are a superfamily of membrane proteins of vast pharmaceutical interest. Here, we describe a graph theory-based analysis of the structure of the ß2 adrenergic receptor (ß2 AR), a prototypical GPCR. In particular, we illustrate the network of direct and indirect interactions that link each amino acid residue to any other residue of the receptor. METHODS: Networks of interconnected amino acid residues in proteins are analogous to social networks of interconnected people. Hence, they can be studied through the same analysis tools typically employed to analyze social networks - or networks in general - to reveal patterns of connectivity, influential members, and dynamicity. We focused on the analysis of closeness-centrality, which is a measure of the overall connectivity distance of the member of a network to all other members. RESULTS: The residues endowed with the highest closeness-centrality are located in the middle of the seven transmembrane domains (TMs). In particular, they are mostly located in the middle of TM2, TM3, TM6 or TM7, while fewer of them are located in the middle of TM1, TM4 or TM5. At the cytosolic end of TM6, the centrality detected for the active structure is markedly lower than that detected for the corresponding residues in the inactive structures. Moreover, several residues acquire centrality when the structures are analyzed in the presence of ligands. Strikingly, there is little overlap between the residues that acquire centrality in the presence of the ligand in the blocker-bound structures and the agonist-bound structures. CONCLUSIONS: Our results reflect the fact that the receptor resembles a bow tie, with a rather tight knot of closely interconnected residues and two ends that fan out in two opposite directions: one toward the extracellular space, which hosts the ligand binding cavity, and one toward the cytosol, which hosts the G protein binding cavity. Moreover, they underscore how interaction network is by the conformational rearrangements concomitant with the activation of the receptor and by the presence of agonists or blockers.