Generalized walks-based centrality measures for complex biological networks

It is well known that protein-protein interaction (PPI) networks are typical evolving complex networks. Identification of important nodes has been an emerging popular topic in complex networks. Many indexes have been proposed to measure the importance of nodes in complex networks, such as degree, closeness, betweenness, k-shell, clustering coefficient, semi-local centrality, eigenvector centrality. Based on multivariate statistical analysis, through integrating the above indexes and further considering the appearances of nodes in network motifs, this paper aims at developing a new measure to characterize the structurally dominant proteins (SDP) in PPI networks. Moreover, we will further investigate the evolution of the defined dominant nodes in temporal evolving real-world and artificial PPI networks. Our results indicate that the constructed artificial networks have some similar statistical properties as those of the real-world evolving networks. In this case, the artificial PPI networks can be used to further investigate the above evolution characteristics of the real-world evolving networks. Simulation results reveal that SDP in the yeast PPI networks are evolutionary conserved, however, the undominant nodes evolve rapidly. Furthermore, PPI networks are very robust against random mutations, while fragile yet with certain robustness to targeted mutations on SDP. Our investigations shed some light on the future applications of the evolving characteristics of bio-molecular networks, such as reengineering of particular networks for technological, synthetic or pharmacological purposes.

SummaryDetermining the centrality of nodes in complex networks provides practical benefits in many areas such as detecting influencer nodes, viral marketing, and preventing the spread of rumors. On the other hand, there is no consensus for the definition of centrality. Therefore, different centrality measures such as degree, closeness, and betweenness have been developed to measure the centrality of a node. However, each centrality measure highlights the various characteristics of the nodes in the network from its own point of view. This causes each centrality measure to rank the nodes in a different order. In recent years, researchers have focused on approaches that combine multiple centrality measures. Thus, the perspectives of different centrality measures can be considered simultaneously. In this study, we have proposed a fast and efficient method using the analytic hierarchy process and entropy weighting to combine multiple centrality measures. We tested the proposed method with synthetic and real datasets and compared the results with those of state‐of‐the‐art methods. The experimental results showed the proposed method to be competitive with these advanced methods, whereas it performed much better than the other methods in terms of computational speed. This indicated that our proposed method could be applied to large and dynamic complex networks.

Influential nodes refer to the ability of a node to spread information in complex networks. Identifying influential nodes is an important problem in complex networks which plays a key role in many applications such as rumor controlling, virus spreading, viral market advertising, research paper views, and citations. Basic measures like degree centrality, betweenness centrality, closeness centrality are identifying influential nodes but they are incapable of largescale networks due to time complexity issues. Chen et al. [1] proposed semi-local centrality, which is reducing computation complexity and finding influential nodes in the network. Recently Yang et al. 2020 [2] proposed a novel centrality measure based on degree and clustering coefficient for identifying the influential nodes. Sanjay et al. 2020 [3] gave voterank and neighborhood coreness-based algorithms for finding the influenced nodes in the network. Zhiwei et al. 2019 [4] considered the average shortest path to discover the influenced node in the network. These are the few recent local,global and mixed centralities. In this paper, we show a broad view of recent methods for finding influential nodes in complex networks. It also analyzes the new challenges and limitations for a better understanding of each method in detail. The experimental results based on these methods show better performance compared with existing basic centrality measures.

Evaluating the importance of nodes in complex networks is an important topic in the research of network characteristics. Its relevant research has a wide range of applications, such as network supervision and rumor control. At present, many methods have been proposed to evaluate the importance of nodes in complex networks, but most of them have the deficiency of one-sided evaluation or too high time complexity. In order to break through the limitations of existing methods, in this paper a novel method of evaluating the importance of complex network nodes is proposed based on Tsallis entropy. This method takes into account both the local and global topological information of the node. It considers the structural hole characteristics and K-shell centrality of the node and fully takes into account the influence of the node itself and its neighboring nodes. To illustrate the effectiveness and applicability of this method, eight real networks are selected from different fields and five existing methods of evaluating node importance are used as comparison methods. On this basis, the monotonicity index, SIR (susceptible-infectious-recovered) model, and Kendall correlation coefficient are used to illustrate the superiority of this method and the relationship among different methods. Experimental results show that this method can effectively and accurately evaluate the importance of nodes in complex networks, distinguish the importance of different nodes significantly, and can show good accuracy of evaluating the node importance under different proportions of nodes. In addition, the time complexity of this method is <inline-formula><tex-math id="M2">\begin{document}$ O({n^2}) $\end{document}</tex-math><alternatives><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="21-20210979_M2.jpg"/><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="21-20210979_M2.png"/></alternatives></inline-formula>, which is suitable for large-scale complex networks.

Advances in proteomic technologies combined with sophisticated computing and modeling methods have generated an unprecedented amount of high-throughput data for system-scale analysis. As a result, the study of protein-protein interaction (PPI) networks has garnered much attention in recent years. One of the most fundamental problems in studying PPI networks is to understand how their architecture originated and evolved to their current state. By investigating how proteins of different ages are connected in the yeast PPI networks, one can deduce their expansion procedure in evolution and how the ancient primitive network expanded and evolved. Studies have shown that proteins are often connected to other proteins of a similar age, suggesting a high degree of age preference between interacting proteins. Though several theories have been proposed to explain this phenomenon, none of them considered protein-clusters as a contributing factor. Here we first investigate the age-dependency of the proteins from the perspective of network motifs. Our analysis confirms that proteins of the same age groups tend to form interacting network motifs; furthermore, those proteins within motifs tend to be within protein complexes and the interactions among them largely contribute to the observed age preference in the yeast PPI networks. In light of these results, we describe a new modeling approach, based on "network motifs", whereby topologically connected protein clusters in the network are treated as single evolutionary units. Instead of modeling single proteins, our approach models the connections and evolutionary relationships of multiple related protein clusters or "network motifs" that are collectively integrated into an existing PPI network. Through simulation studies, we found that the "network motif" modeling approach can capture yeast PPI network properties better than if individual proteins were considered to be the simplest evolutionary units. Our approach provides a fresh perspective on modeling the evolution of yeast PPI networks, specifically that PPI networks may have a much higher age-dependency of interaction density than had been previously envisioned.

Identifying influential nodes in complex networks is essential for network robust and stability, such as viral marketing and information control. Various methods have been proposed to define the influence of nodes. In this paper, we comprehensively consider the global position and local structure to identify influential nodes. The number of iterations in the process of k-shell decomposition is taken into consideration, and the improved k-shell decomposition is then put forward. The improved k-shell decomposition and degree of target node are taken as the benchmark centrality, in addition, as is well known, the effect between node pairs is inversely proportional to the shortest path length between two nodes, and then we also consider the effect of neighbors on target node. To evaluate the performance of the proposed method, susceptible-infected (SI) model is adopted to simulate the spreading process in four real networks, and the experimental results show that the proposed method has obvious advantages over classical centrality measures in identifying influential nodes.

A novel potential edge weight method for identifying influential nodes in complex networks based on neighborhood and position

Protein-protein interaction (PPI) networks provide a well-established framework for elucidating structural properties. In contrast, much greater effort is required to identify useful and/or hidden information using the approach because of the complexity of the networks. Accordingly, an appropriate methodology that allows characterization of a simple, but core, sub-network of a complex network would be a potentially valuable alternative approach. Here, we employed k-core decomposition as a useful tool for obtaining core sub-networks from the complex PPI network in yeast. To apply a k-core value to the complex yeast PPI network, we constructed cytoplasmic and nuclear core sub-networks. We measured the lethality of proteins and the ratio of hub to non-hub core sub-network proteins at each k-core value step. With increasing k-core value, the values of the two parameters gradually increased. Application of 6- and 7-core values to cytoplasmic and nuclear PPI networks yielded modular, structured core sub-networks that were functionally specialized. We also elucidated a false hub: a structural hub exhibiting no functional roles or lethal properties in the network. By employing k-core decomposition to cytoplasmic and nuclear PPI networks in yeast, we obtained useful and/or hidden information during the core sub-network construction process, indicating that k-core decomposition is a useful tool for structural and informational network studies. Notably, we found false hub proteins that might provide insight into protein networks and clues to understanding network evolution.

Identifying the vital nodes in networks is of great significance for understanding the function of nodes and the nature of networks. Many centrality indices, such as betweenness centrality (BC), eccentricity centrality (EC), closeness centricity (CC), structural holes (SH), degree centrality (DC), PageRank (PR) and eigenvector centrality (VC), have been proposed to identify the influential nodes of networks. However, some of these indices have limited application scopes. EC and CC are generally only applicable to undirected networks, while PR and VC are generally used for directed networks. To design a more applicable centrality measure, two vital node identification algorithms based on node adjacency information entropy are proposed in this paper. To validate the effectiveness and applicability of the proposed algorithms, contrast experiments are conducted with the BC, EC, CC, SH, DC, PR and VC indices in different kinds of networks. The results show that the index in this paper has a high correlation with the local metric DC, and it also has a certain correlation with the PR and VC indices for directed networks. In addition, the experimental results indicate that our algorithms can effectively identify the vital nodes in different networks.

A novel method of evaluating key nodes in complex networks

Identification of influential vertices plays a very prominent task in a complex network. So, the fundamental task in complex networks is to determine the influential nodes whose expulsion crucially cutoff network harmony. The analysis of the network’s topological characteristics, such as susceptibility and resilience, can be aided by identifying influential nodes. This work uses the notion of Maximize the Number of Connected Components Problem, which helps in determining influential nodes, and whose removal yields optimum number of connected components. This work includes application of topology-based centrality measures on real-world networks. However, conventional methods fail to detect most influential nodes that cause the network to split into the optimum number of components. To address this, our work introduces new centrality called global isolating centrality with half of the diameter hops, that focus on network connectedness. The results reveal that the new centrality is better than the existing centralities for certain probability values.

Online environments have evolved from the early-stage technical systems to social platforms with social communication mechanisms resembling the interactions which can be found in the real world. Online marketers are using the close relations between the users of social networks to more easily propagate the marketing contents in their advertising campaigns. Such viral marketing campaigns have proven to provide better results than traditional online marketing, hence the increasing research interest in the topic. While the majority of the up-to-date research focuses on maximizing the global coverage and influence in the complete network, some studies have been conducted in the area of budget-constrained conditions as well as in the area of targeting particular groups of nodes. In this paper, a novel approach to targeting multi-attribute nodes in complex networks is presented, in which an MCDA method with various preference weights for all criteria is used to select the initial seeds to best reach the targeted nodes in the network. The proposed approach shows some symmetric characteristics—while the global coverage in the network is decreased, the coverage amongst the targeted nodes grows.

The issue of mining influential nodes in complex networks is a topic of immense interest. Recently, many methods have been proposed, but they suffer from certain limitations. In this article, a novel centrality measure based on local fuzzy information centrality (LFIC) is proposed. LFIC puts forward the concept that the inner structure of a node’s box contains information about the node’s importance. LFIC uses the amount of information contained in the node’s box as a measure of its importance. In LFIC, the uncertainty of information contained in nodes’ boxes is measured by the improved Shannon entropy. Most importantly, fuzzy logic is applied to deal with the uncertainty of neighbor nodes’ contributions to the center node’s importance, which is neglected by most existing methods. To verify the effectiveness of our proposed method, six existing methods are used for comparison and five experiments are conducted using six real-world complex networks. The experimental results indicate that the influential nodes identified by LFIC can cause a wider scope of infection in networks and have a larger effect on the network connectivity, thereby proving the effectiveness and accuracy of LFIC. The correlation between nodes’ LFIC values and their real infection ability is highly positive according to Kendall’s tau coefficient, proving LFIC’s credibility and superiority. The extension of LFIC, namely the bi-directional local fuzzy information centrality, is also proposed to explore its feasibility in weighted directed complex networks.

The volume of available data in recent years has rapidly increased. In consequence, datasets commonly end up with many irrelevant features. That increase may disturb human understanding and even lead to poor machine learning models. This research proposes a novel feature ranking method that employs trees from a Random Forest to transform a dataset into a complex network to which centrality measures are applied to rank the features. That process takes place by representing each tree as a graph where all the tree features are vertices on this graph, and the links within the nodes (father \(\rightarrow \) child) of the tree are represented by a weighted edge between the two respective vertices. The union of all graphs from individual trees leads to the complex network. Then, three centrality measures are applied to rank the features in the complex network. Experiments were performed in eighty-five supervised classification datasets, with a variation in the feature noise level, to evaluate our novel method. Results show that centrality measures in non-oriented complex networks are comparable and may be correlated to the Random Forest’s variable importance ranking algorithm. Vertex strength and eigenvector outperformed the Random Forest in 40% noise datasets, with a not statistically different result at a 95% confidence level.KeywordsFeature rankingRandom ForestComplex networksCentrality measures

BackgroundBiological systems can be modeled as complex network systems with many interactions between the components. These interactions give rise to the function and behavior of that system. For example, the protein-protein interaction network is the physical basis of multiple cellular functions. One goal of emerging systems biology is to analyze very large complex biological networks such as protein-protein interaction networks, metabolic networks, and regulatory networks to identify functional modules and assign functions to certain components of the system. Network modules do not occur by chance, so identification of modules is likely to capture the biologically meaningful interactions in large-scale PPI data. Unfortunately, existing computer-based clustering methods developed to find those modules are either not so accurate or too slow.ResultsWe devised a new methodology called SCAN (Structural Clustering Algorithm for Networks) that can efficiently find clusters or functional modules in complex biological networks as well as hubs and outliers. More specifically, we demonstrated that we can find functional modules in complex networks and classify nodes into various roles based on their structures. In this study, we showed the effectiveness of our methodology using the budding yeast (Saccharomyces cerevisiae) protein-protein interaction network. To validate our clustering results, we compared our clusters with the known functions of each protein. Our predicted functional modules achieved very high purity comparing with state-of-the-art approaches. Additionally the theoretical and empirical analysis demonstrated a linear running-time of the algorithm, which is the fastest approach for networks.ConclusionWe compare our algorithm with well-known modularity based clustering algorithm CNM. We successfully detect functional groups that are annotated with putative GO terms. Top-10 clusters with minimum p-value theoretically prove that newly proposed algorithm partitions network more accurately then CNM. Furthermore, manual interpretations of functional groups found by SCAN show superior performance over CNM.