scholarly journals A systematic survey of centrality measures for protein-protein interaction networks

2017 ◽  
Author(s):  
Minoo Ashtiani ◽  
Ali Salehzadeh-Yazdi ◽  
Zahra Razaghi-Moghadam ◽  
Holger Hennig ◽  
Olaf Wolkenhauer ◽  
...  

AbstractBackgroundNumerous 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.

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Milagros Marín ◽  
Francisco J. Esteban ◽  
Hilario Ramírez-Rodrigo ◽  
Eduardo Ros ◽  
María José Sáez-Lara

Abstract Background Biologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein interaction networks can identify the most relevant structures directly tied to biological functions. Functional enrichments can then be performed based on these structural aspects of gene relationships for the study of channelopathies. Channelopathies refer to a complex group of disorders resulting from dysfunctional ion channels with distinct polygenic manifestations. This study presents a semi-automatic workflow using protein-protein interaction networks that can identify the most relevant genes and their biological processes and pathways in channelopathies to better understand their etiopathogenesis. In addition, the clinical manifestations that are strongly associated with these genes are also identified as the most characteristic in this complex group of diseases. Results In particular, a set of nine representative disease-related genes was detected, these being the most significant genes in relation to their roles in channelopathies. In this way we attested the implication of some voltage-gated sodium (SCN1A, SCN2A, SCN4A, SCN4B, SCN5A, SCN9A) and potassium (KCNQ2, KCNH2) channels in cardiovascular diseases, epilepsies, febrile seizures, headache disorders, neuromuscular, neurodegenerative diseases or neurobehavioral manifestations. We also revealed the role of Ankyrin-G (ANK3) in the neurodegenerative and neurobehavioral disorders as well as the implication of these genes in other systems, such as the immunological or endocrine systems. Conclusions This research provides a systems biology approach to extract information from interaction networks of gene expression. We show how large-scale computational integration of heterogeneous datasets, PPI network analyses, functional databases and published literature may support the detection and assessment of possible potential therapeutic targets in the disease. Applying our workflow makes it feasible to spot the most relevant genes and unknown relationships in channelopathies and shows its potential as a first-step approach to identify both genes and functional interactions in clinical-knowledge scenarios of target diseases. Methods An initial gene pool is previously defined by searching general databases under a specific semantic framework. From the resulting interaction network, a subset of genes are identified as the most relevant through the workflow that includes centrality measures and other filtering and enrichment databases.


2018 ◽  
Vol 12 (1) ◽  
Author(s):  
Minoo Ashtiani ◽  
Ali Salehzadeh-Yazdi ◽  
Zahra Razaghi-Moghadam ◽  
Holger Hennig ◽  
Olaf Wolkenhauer ◽  
...  

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