PPI network reconstruction

The protein-protein interactions (PPIs) were predicted based on data deposited in the Search Tool for the Retrieval of Interacting Genes/Genomes (STRING) database, with a confidence score > 0.7. The reconstructed protein-protein pairs included functional relationships of proteins from five sources: published high-throughput experiments, genomic context prediction, co-expression, automated text mining, and PPI deposited in other databases. Reconstructed PPI networks were visualised as undirected or hierarchical networks using Cytoscape. To identify hub proteins most interconnected with their neighbours in the PPI network node, degree scores were calculated using NetworkAnalyzer plugin [50], and degree centrality values of the nodes were visualised as heatmaps using the Morpheus tool (https://software.broadinstitute.org/morpheus/). A cut-off criterion to identify hub genes/proteins is degree of node more than 10 within the analysed network.