D574 Nucleic Acids Research, 2011, Vol. 39, Database issue installation are provided through our ftp website or by simple request. PHEVER WEB INTERFACE The PhEVER web interface allows for two query forms represented in Figure 4A and B. On the one hand (Figure 4A), the HoSeqI tool allows to search in PhEVER families with a user provided query (15). This query is used to BLAST the proteins present in PhEVER and to match the most related family. Alignments and phylogenies for this new family containing the user provided sequence can be recomputed on the ﬂy, visualized and manipulated with Java applets (Figure 4F) (31,32). On the other hand (Figure 4B), the query tool allows to directly query the database with a very diverse range of terms including gene name, anno- tation term, species name, protein accession number, genome accession number and family accession number. The species and sequences represented in each family detected by the query can then be viewed (Figure 4D) as well as the alignments and phylogenies which can be edited online via Java applets (Figure 4E) (31,32). More details on how to query PhEVER are presented in the Supplementary Data. CONCLUSION AND PERSPECTIVES PhEVER is the ﬁrst open access database to provide information at the cross-taxa scale for the analysis of virus–virus and virus–host protein transfers. It compiles information from all kingdoms of life, and handles data from the genomes of all completely sequenced viruses and prokaryotes and of a large range of eukaryotes. It is the largest database of viral homologous families and offers highly accurate pre-computed alignments and phylogenies, making it a powerful tool for the analysis of horizontal gene transfer and more widely for the analysis of gene history. Our objective is to continue the development of PhEVER around the analysis of protein evolution in the context of virus–virus and virus–host interactions. More speciﬁcally, the next step we have under development is the detection of evolutionary conserved modules in the proteins present in PhEVER. Indeed, there is strong evidence that proteins evolve in a modular way, where modules are deﬁned as parts of proteins sharing a common evolutionary history. These modules act as small interchangeable blocks of sequences that may be combined into proteins and form novel functions (33–35). We are interested in providing a global tool allowing to analyse the weight of modular evolution in viral adaptation. We will therefore implement the detec- tion of modules in PhEVER proteins to provide informa- tion concerning the exchanges of genetic information at the sub-protein level. In conclusion, PhEVER aims at being a comprehensive tool for the analysis of virus–virus and virus–host relation- ships from an evolutionary point of view, namely through the analysis of genomic interchanges. It should become a valuable tool for anyone working on viral evolution, but also to understand the general mechanisms behind protein evolution and functional innovation. DATABASE ACCESS AND UPDATES Public access and documentation is freely available through the database webpage (http://pbil.univ-lyon1.fr/ databases/phever/) and through all dedicated ACNUC re- trieval systems. More information on dedicated ACNUC retrieval systems, such as standalone query software (16), the seqinR package for R (30) or the C and Python APIs, can be obtained in the Supplementary Data or on the PhEVER webpage. The PhEVER ﬂat ﬁles for local instal- lation are available through our ftp server (ftp://pbil.univ lyon1.fr/pub/phever) and instructions are available on the database webpage. The PhEVER database is updated every 6 months. This update frequency allows to follow the fast pace of viral and prokaryotic genome sequencing as well as to obtain updated genomic annotations for large eukaryotic genomes. Previous versions of the database remain available upon request. SUPPLEMENTARY DATA Supplementary Data are available at NAR Online. ACKNOWLEDGEMENTS The authors wish to thank Vincent Navratil and Vincent Daubin for helpful dicussions as well as Linda Artmann for assisting the ﬁgure preparation. The authors also ac- knowledge the CC IN2P3 (Villeurbanne) for the computing resources and Pascal Calvat for his technical help as well as the computer department at PBIL-DOUA and LBBE for assistance and maintenance of the PhEVER server. FUNDING Interaubio project, granted by the Re´ gion Rhoˆ ne-Alpes. The Re´ gion Rhoˆ ne-Alpes and the University of Lie` ge (to L.P.). Funding for open access charge: BAMBOO Team, INRIA Rhoˆ ne-Alpes. Conﬂict of interest statement. 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