The clustering of proteins into homologous families was constructed using an automated procedure similar to the one described in (14) and implemented within a parallel framework in a software package called SiLiX. Briefly, sequences were assigned to protein families by simple transitive link using the following criteria. A similarity search of all translated proteins and mature peptides against all was performed using BLASTP2 similarity search with the BLOSUM62 substitution matrix, a 10 À4 e-value threshold and the 'm S' filter option (22, 23) . For each pair of sequences, HSPs which were not compatible with a global alignment were removed. Two sequences were included in the same family if the sum of the remaining HSPs covered >80% of the proteins length (and at least 100 amino acids) and if their identity was !35%. These two criteria were previously shown to provide a good trade-off between the ability of clustering sequences from divergent organisms and the quality of resulting alignments for subsequent phylogenetic analyses (14) . Finally, only families containing at least one viral sequence were integrated in the database. For each of the families, a small description built from the gene annotations ordered by frequency is available on the web interface. Figure 2 presents the distribution of viral species, proteins and families according to each viral group (A) as well as a Venn diagram representing the families content (B). Figure 2A presents PhEVER's broad taxonomical distribution covering all Baltimore groups (24). This distribution is naturally biased towards dsDNA, ssDNA and positive-sense ssRNA viruses reflecting the bias in genomic sequencing efforts. Indeed these groups contain long-studied viral families-either for their medical interest or for their economical impacts-such as Caudovirales, Poxviridae, Herpesvirales, Flaviviridae, Picornavirales or Parvoviridae. Figure 2 (B) shows a large number of orphan families indicating that a significant proportion of viral proteins (32%) do not contain any homologs with proteins from known genomes. These proteins, among which some might possibly be caused by annotation errors, are unfit for comparative functional analysis and should be the focus of future experimental studies to validate them and to provide with crucial information on viral mechanisms. Figure 2B also shows the small number of families sharing sequences from both viruses and eukaryotes compared to the relatively high number of families sharing sequences from both viruses and bacteria. This observation may be due to different underlying biological mechanisms but might also be an indicator of a still low coverage of the Eukarya domain.