EvoPPI 2: A Web and Local Platform for the Comparison of Protein–Protein Interaction Data from Multiple Sources from the Same and Distinct Species

The understanding of the molecular basis of cellular processes and ultimately disease, requires knowledge on protein structures, interactions, and functions. Protein–protein interaction data (PPI) is available in the publicly available main PPI databases that show little overlap due to the use of different criteria. Therefore, web platforms that aggregate the data from multiple sources, such as EvoPPI ( http://evoppi.i3s.up.pt ), where the existing databases have been updated and new ones were added, as here described, and APID ( http://cicblade.dep.usal.es:8080/APID/init.action ) are useful. Still, in both EvoPPI 1.0 and 2, here presented, we have made a special effort to make it flexible in what concerns the choice of the databases to be compared. Moreover, interacting protein pairs tend to be evolutionarily conserved, and thus the information available for one species might be used to predict the incompleteness of the network in another one, and identify putative missing interactions. This approach is now available in EvoPPI 2 for Homo sapiens and the model species Mus musculus, Caenorhabditis elegans, and Drosophila melanogaster, using either Ensembl ( https://www.ensembl.org ) or DIOPT Ortholog Finder ( https://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl ) orthologies/paralogies. Moreover, since not all available PPI data is present in the main databases (e.g. PPI observed in patient tissues and mutant animal species, where PPI might be aberrant, are usually not included in the main databases, although in several studies this has been shown not to be the case), we provide the needed tools (including a Lubuntu-based virtual machine where all software is already installed and ready-to-run) to run a local EvoPPI 2 instance and create a custom database from the existing ones. This way the user can add new data for any species and from any source database, creating custom interactomes. Administrator tools are provided to help in the automatic processing and conversion of files from various sources into the custom EvoPPI database format.