D298 Nucleic Acids Research, 2010, Vol. 38, Database issue Figure 1. The Gene3D genome coverage visualizer. Genome coverage—the number of genes with a match to a CATH superfamily—can be viewed using the new visualization web tool (http://gene3d.biochem.ucl.ac.uk:8090/GenomeCoverageGraphs/). Coverage for a speciﬁc superfamily can be retrieved using the top query bar. In the left-hand column, species can be removed from the graph or their species names manually edited. New species can be added via tables found by selecting the ‘Database Summaries’, ‘Ensembl Genome Data’ and ‘Integr8 Genome Data’ tab headers. superfamily a protein domain belongs to, or proteins in the human genome with a speciﬁc GO term—and retrieve that subset or superset for further investigation. A query chain can be built up and followed by means of the ‘breadcrumb trail’ on the front summary tab in the results views. Imported annotations and descriptions, such as Pfam families (13), are also linked to the source database. New genome assemblies and displays The Ensembl Metazoa genome assemblies have been added to the Gene3D sequence database (currently Ensembl 55). All transcripts are included and individually scanned. Users may query using Ensembl gene, transcript and protein identiﬁers; mappings to UniProt and RefSeq identiﬁers are also shown. Gene3D annotates two sets of sequenced genomes: eukaryotic transcripts from Ensembl metazoan (49 species) and UniProt-based assemblies for archaea, bacteria and eukaryotes (1085 species) from Integr8 (14). In addition, a new dynamic web application for querying and visualizing genome coverage for speciﬁc superfamilies and genomes is available at: http://gene3d .biochem.ucl.ac.uk:8090/GenomeCoverageGraphs (Figure 1). As can be seen, coverage for diﬀerent genomes can vary signiﬁcantly, although this could reﬂect biases in gene annotation in addition to variation in domain content. Phylogenetic proﬁles for Ensembl 55 metazoa and Integr8 prokaryotes for the CATH-Gene3D superfamilies are available for download from the Gene3D FTP site (ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/CURRENT _RELEASE/). A new aspect to the genome annotation is the inclusion of non-synonymous single-nucleotide polymorphisms (SNPs) and other sequence variants from Ensembl Variation (11). These are included in the protein feature display, allowing the correlation of altered activity or phenotype with other annotations, such as the location of binding sites or domains. Sequence features and domain architectures The Gene3D website uses a graphics package kindly provided by Pfam to draw sequence feature annotations (Figure 2), including domains, active sites, SNP locations, transmembrane regions, signal peptides and others. This has now been localized to the Gene3D server, greatly improving rendering speeds and site stability. For the single protein view (see above) a detailed description of the protein is provided (the ‘Features’ tab), with one ‘track’ per annotation type. A second visualization view (‘Sequence Image’) amalgamates all the annotations into a single ‘track’. The ‘Sequence Image’ tab is also available in the collection view (e.g. for a superfamily), along with a tab displaying the set of distinct multi-domain architectures found (‘Multi-Domain Architectures’). A useful facility of Gene3D is the inclusion of CATH domains based on the Protein Data Bank (PDB). We now use the SIFTS PDB-to-UniProt mapping, which has increased the number of domains we are able to map to Gene3D (15). Molecular function, interactions, pathways and orthologues The parsing and import of UniProt records has been improved, leading to more descriptive terms being imported along with more associated information. We have also added EggNOG orthologue assignments (16). EggNog orthologue families are generated by large-scale clustering of protein sequences using an extension of the COGS protocol and applying a rule-based annotation system.