VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus–host interaction networks

Navratil, Vincent; de Chassey, Benoît; Meyniel, Laurène; Delmotte, Stéphane; Gautier, Christian; André, Patrice; Lotteau, Vincent; Rabourdin-Combe, Chantal

The low level of redundancy observed among available databases involved in molecular interactions management has emphasized the need to integrate these heterogeneous data sources (23) . Virus-virus, virus-host and host-host protein-protein interactions and meta-data related to experimental procedures or publications were extracted from 10 databases (BIND, MINT, INTACT, HPRD, DIP, BIOGRID, REACTOME, GENERIF, HIV-GENERIF, NETWORKIN) ( Figure 1 ). Due to the heterogeneity of protein sequence identification found across these databases (i.e. gene identification number, gene name, protein accession number, protein name), NCBI and ENSEMBL protein sequence databases were chosen to unify virus and host proteins respectively (see Supplementary Table 1A) . Towards this end, the IPI database system (31) was chosen to cross-reference all the human protein sequences to ENSEMBL protein accession numbers. In addition, viral protein sequences defined at EMBL and UNIPROT were mapped on NCBI protein sequences by using BLAST Alignment software (32) . Protein cross-referencing led to the definition of nonredundant protein-protein interactions that were in many cases defined in different databases, publications or supported by distinct experimental procedures (see Supplementary Table 1B) . Thus, all information associated with non-redundant interactions, like database origin, experimental procedure description in PSI-MI 2.5 standard format (33) or PUBMED identification (PMID) number, were retrieved in VirHostNet to provide the most documented interactions. This compilation of interaction meta-data will facilitate data quality filtering based on the number of databases, methods or PMIDs used (34, 35) .