is identiﬁed. Such sequence-based queries help to circum- vent potential ambiguities arising from multiple gene iden- tiﬁers or synonyms from alternative resources or database releases. Query history. Queries are stored during each user’s web browser session to enable reviewing and re-running of their recently executed queries. The type of search and the level in the species phylogeny at which it was per- formed, together with the number of orthologous groups returned, are displayed for each query. The user may re-run or delete individual queries or clear their complete query history. Data export. The data for each orthologous group may be exported as either a Fasta-formatted ﬁle of protein se- quences or a tab-delimited text ﬁle of members with their InterPro annotations. In addition, data for the complete set of groups retrieved from any OrthoDB query may be exported as both Fasta-formatted sequence and tab-delimited annotation ﬁles. The ‘Print Tables’ option exports the data tables for all retrieved groups to a printer-friendly HTML-formatted document that may be printed or saved as required. OrthoDB links. OrthoDB data are cross-referenced with numerous biological databases, linking retrieved orthologous group gene members to their respective sources and allowing direct access to additional informa- tion. In addition, OrthoDB groups are referenced through link-outs from major community resources including UniProt and Flybase. SUPPLEMENTARY DATA Supplementary Data are available at NAR Online. ACKNOWLEDGEMENTS The authors would like to thank Dr Ivo Pedruzzi and all members of the Computational Evolutionary Genomics Group for useful suggestions and discussions. FUNDING The Swiss National Science Foundation (31003A-125350). Funding for open access charge: Swiss Institute of Bioinformatics. Conﬂict of interest statement. None declared. REFERENCES 1. Fitch,W. (1970) Distinguishing homologous from analogous proteins. Syst. Zool., 19, 99–113. 2. Koonin,E. (2005) Orthologs, paralogs, and evolutionary genomics. Annu. Rev. Genet., 39, 309–338. 3. Sonnhammer,E. and Koonin,E. (2002) Orthology, paralogy and proposed classiﬁcation for paralog subtypes. Trends Genet., 18, 619–620. Nucleic Acids Research, 2011, Vol. 39, Database issue D287 4. Fang,G., Bhardwaj,N., Robilotto,R. and Gerstein,M. (2010) Getting started in gene orthology and functional analysis. PLoS Comput. Biol., 6, e1000703. 5. Altenhoff,A. and Dessimoz,C. (2009) Phylogenetic and functional assessment of orthologs inference projects and methods. PLoS Comput. Biol., 5, e1000262. 6. Tatusov,R., Fedorova,N., Jackson,J., Jacobs,A., Kiryutin,B., Koonin,E., Krylov,D., Mazumder,R., Mekhedov,S., Nikolskaya,A. et al. (2003) The COG database: an updated version includes eukaryotes. BMC Bioinformatics, 4, 41. 7. Muller,J., Szklarczyk,D., Julien,P., Letunic,I., Roth,A., Kuhn,M., Powell,S., von Mering,C., Doerks,T., Jensen,L. et al. (2010) eggNOG v2.0: extending the evolutionary genealogy of genes with enhanced non-supervised orthologous groups, species and functional annotations. Nucleic Acids Res., 38, D190–D195. 8. Ostlund,G., Schmitt,T., Forslund,K., Ko¨ stler,T., Messina,D., Roopra,S., Frings,O. and Sonnhammer,E. (2010) InParanoid 7: new algorithms and tools for eukaryotic orthology analysis. Nucleic Acids Res., 38, D196–D203. 9. Roth,A., Gonnet,G. and Dessimoz,C. (2008) Algorithm of OMA for large-scale orthology inference. BMC Bioinformatics, 9, 518. 10. Kriventseva,E., Rahman,N., Espinosa,O. and Zdobnov,E. (2008) OrthoDB: the hierarchical catalog of eukaryotic orthologs. Nucleic Acids Res., 36, D271–D275. 11. Chen,F., Mackey,A., Stoeckert,C.J. and Roos,D. (2006) OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Res., 34, D363–D368. 12. Deluca,T., Wu,I., Pu,J., Monaghan,T., Peshkin,L., Singh,S. and Wall,D. (2006) Roundup: a multi-genome repository of orthologs and evolutionary distances. Bioinformatics, 22, 2044–2046. 13. Vilella,A., Severin,J., Ureta-Vidal,A., Heng,L., Durbin,R. and Birney,E. (2009) EnsemblCompara GeneTrees: complete, duplication-aware phylogenetic trees in vertebrates. Genome Res., 19, 327–335. 14. van der Heijden,R., Snel,B., van Noort,V. and Huynen,M. (2007) Orthology prediction at scalable resolution by phylogenetic tree analysis. BMC Bioinformatics, 8, 83. 15. Mi,H., Dong,Q., Muruganujan,A., Gaudet,P., Lewis,S. and Thomas,P. (2010) PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium. Nucleic Acids Res., 38, D204–D210. 16. Datta,R., Meacham,C., Samad,B., Neyer,C. and Sjo¨ lander,K. (2009) Berkeley PHOG: PhyloFacts orthology group prediction web server. Nucleic Acids Res., 37, W84–W89. 17. Huerta-Cepas,J., Bueno,A., Dopazo,J. and Gabaldo´ n,T. (2008) PhylomeDB: a database for genome-wide collections of gene phylogenies. Nucleic Acids Res., 36, D491–D496. 18. Wapinski,I., Pfeffer,A., Friedman,N. and Regev,A. (2007) Automatic genome-wide reconstruction of phylogenetic gene trees. Bioinformatics, 23, i549–i558. 19. Ruan,J., Li,H., Chen,Z., Coghlan,A., Coin,L., Guo,Y., H e´riche´ ,J., Hu,Y., Kristiansen,K., Li,R. et al. (2008) TreeFam: 2008 update. Nucleic Acids Res., 36, D735–D740. 20. Duret,L., Mouchiroud,D. and Gouy,M. (1994) HOVERGEN: a database of homologous vertebrate genes. Nucleic Acids Res., 22, 2360–2365. 21. Tatusov,R., Koonin,E. and Lipman,D. (1997) A genomic perspective on protein families. Science, 278, 631–637. 22. Hahn,M. (2009) Distinguishing among evolutionary models for the maintenance of gene duplicates. J. Hered., 100, 605–617. 23. Wilson,C., Kreychman,J. and Gerstein,M. (2000) Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores. J. Mol. Biol., 297, 233–249. 24. UniProt-Consortium. (2010) The Universal Protein Resource (UniProt) in 2010. Nucleic Acids Res., 38, D142–D148. 25. Tweedie,S., Ashburner,M., Falls,K., Leyland,P., McQuilton,P., Marygold,S., Millburn,G., Osumi-Sutherland,D., Schroeder,A., Seal,R. et al. (2009) FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Res., 37, D555–D559. 26. Smith,T. and Waterman,M. (1981) Identiﬁcation of common molecular subsequences. J. Mol. Biol., 147, 195–197. 27. Saebø,P., Andersen,S., Myrseth,J., Laerdahl,J. and Rognes,T. (2005) PARALIGN: rapid and sensitive sequence similarity