Abstract

BackgroundNumerous centrality measures have been introduced to identify “central” nodes in large networks. The availability of a wide range of measures for ranking influential nodes leaves the user to decide which measure may best suit the analysis of a given network. The choice of a suitable measure is furthermore complicated by the impact of the network topology on ranking influential nodes by centrality measures. To approach this problem systematically, we examined the centrality profile of nodes of yeast protein-protein interaction networks (PPINs) in order to detect which centrality measure is succeeding in predicting influential proteins. We studied how different topological network features are reflected in a large set of commonly used centrality measures.ResultsWe used yeast PPINs to compare 27 common of centrality measures. The measures characterize and assort influential nodes of the networks. We applied principal component analysis (PCA) and hierarchical clustering and found that the most informative measures depend on the network’s topology. Interestingly, some measures had a high level of contribution in comparison to others in all PPINs, namely Latora closeness, Decay, Lin, Freeman closeness, Diffusion, Residual closeness and Average distance centralities.ConclusionsThe choice of a suitable set of centrality measures is crucial for inferring important functional properties of a network. We concluded that undertaking data reduction using unsupervised machine learning methods helps to choose appropriate variables (centrality measures). Hence, we proposed identifying the contribution proportions of the centrality measures with PCA as a prerequisite step of network analysis before inferring functional consequences, e.g., essentiality of a node.

Highlights

  • Numerous centrality measures have been introduced to identify “central” nodes in large networks

  • Ernesto Estrada generalized this rule to six other centrality measures. He showed that the Subgraph centrality measure scored best compared to classic measures to find influential proteins, and generally using these measures performed significantly better than a random selection [16]

  • To validate the principal component analysis (PCA) results in Protein-protein interaction network (PPIN), we examined whether the centrality measures in all networks can be clustered according to clustering tendency procedure

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Summary

Introduction

Numerous centrality measures have been introduced to identify “central” nodes in large networks. The choice of a suitable measure is complicated by the impact of the network topology on ranking influential nodes by centrality measures. To approach this problem systematically, we examined the centrality profile of nodes of yeast protein-protein interaction networks (PPINs) in order to detect which centrality measure is succeeding in predicting influential proteins. Various computational methods have been proposed to predict and prioritize influential nodes (e.g. proteins) among biological networks. Network-based ranking (i.e. centrality analysis) of biological components has been widely used to find influential nodes in large networks, with applications in biomarker discovery, drug design and drug repurposing [2,3,4,5,6]. Several centralities measures (mostly in the context of social network analyses)

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