Network construction and topology features

Our analysis was performed on PPI networks of human proteins and P. vivax proteins. The networks were obtained from the STRING database (version 11.0). ³⁷ To ensure that only reliable interactions were obtained, interactions with a high confidence score (>900) were retained. A total of 12 038 human proteins with 313 359 interactions and 1787 P. vivax proteins with 11 477 interactions were obtained. Subsequently, a heterogeneous network was constructed by connecting human-human protein interactions and P. vivax-P. vivax protein interactions with the human-P. vivax protein associations.

The network topology features of all proteins were extracted based on centrality measurements. Several studies have shown that a relationship exists between gene essentiality and network centrality in PPI networks.^38-40 Thus, we further investigated 5 topological features: betweenness centrality, closeness centrality, degree, eccentricity, and Kleinberg’s hub centrality. Each of these features explained different aspects of the measurement. Betweenness centrality reflects an important node in term of overloading paths passing through it in the communication of the network.^35,36 Closeness centrality measures how close a given node is to the other nodes in the network.^35,36 The degree represents the level of the local connections of a given node.^35,36 Eccentricity calculates the local density of the connections among neighboring nodes of a given node. The Kleinberg’s hub measures the importance of a given node connecting the other important nodes. ³⁶