eggNOG v4.0: Nested orthology inference across 3686 organisms

Sean Powell, Kristoffer Forslund, Damian Szklarczyk, Kalliopi Trachana, Alexander Roth, Jaime Huerta-Cepas, Toni Gabaldón, Thomas Rattei, Chris Creevey, Michael Kuhn, Lars J. Jensen, Christian von Mering, Peer Bork

Research output: Contribution to journalArticlepeer-review

469 Citations (Scopus)
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With the increasing availability of various ‘omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.
Original languageEnglish
Pages (from-to)D231-D239
Number of pages9
JournalNucleic Acids Research
Issue numberD1
Early online date30 Nov 2013
Publication statusPublished - 01 Jan 2014


  • Databases, Genetic
  • Genome
  • Genome, Microbial
  • Genomics
  • Internet
  • Molecular Sequence Annotation
  • Multigene Family
  • Phylogeny
  • Proteins
  • Sequence Homology, Amino Acid


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