Abstract
The availability of large-scale screens of host-virus interaction interfaces enabled the topological analysis of viral protein targets of the host. In particular, host proteins that bind viral proteins are generally hubs and proteins with high betweenness centrality. Recently, other topological measures were introduced that a virus may tap to infect a host cell. Utilizing experimentally determined sets of human protein targets from Herpes, Hepatitis, HIV and Influenza, we pooled molecular interactions between proteins from different pathway databases. Apart from a protein’s degree and betweenness centrality, we considered a protein’s pathway participation, ability to topologically control a network and protein PageRank index. In particular, we found that proteins with increasing values of such measures tend to accumulate viral targets and distinguish viral targets from non-targets. Furthermore, all such topological measures strongly correlate with the occurrence of a given protein in different pathways. Building a random forest classifier that is based on such topological measures, we found that protein PageRank index had the highest impact on the classification of viral (non-)targets while proteins' ability to topologically control an interaction network played the least important role.
Highlights
The arrival of high-throughput screens that allow the generation of large datasets of protein interactions has enabled scientists to comprehensively understand the ways different proteins interact with each other within and between cells
Previous approaches tout the role of the simple degree and betweenness centrality as topological features in molecular interaction networks that viruses and other pathogens tap
We considered the number of pathways that a protein appeared in as a potential pathogen feature, as viruses may thoroughly penetrate a host system by reaching into many different pathways
Summary
The arrival of high-throughput screens that allow the generation of large datasets of protein interactions has enabled scientists to comprehensively understand the ways different proteins interact with each other within and between cells. Protein interaction interfaces of several human pathogens and their human host cells have been experimentally determined [1,2,3,4,5,6,7], indicating physical interactions between viral and human host proteins. Interaction interfaces of several other pathogens such as bacteriophages [8] and parasites [9] have been investigated as well. Various RNAi screens have revealed sets of human proteins required by different human viruses to infect their host cells [10,11,12].
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