CoChat
Sign Up
Cited by 652Genomics and Phylogenetic StudiesBioinformatics and Genomic NetworksChromosomal and Genetic Variations

eggNOG v4.0: nested orthology inference across 3686 organisms

Open access
Powell, Sean, Forslund, Kristoffer, Szklarczyk, Damian, Trachana, Kalliopi, Roth, Alexander, Huerta-Cepas, Jaime, Gabaldón, Toni, Rattei, Thomas +5 more·2014·Nucleic Acids Research
DOI 10.1093/nar/gkt1253PMC PMC3964997
Open this paper in CoChat — free accountOpen PDF

Abstract

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 http://eggnog.embl.de) 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/nar/gkt1253

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Genes that diverged at a speciation node are orthologs, and those that diverged at a duplication node are paralogs.

    “Genes that diverged at a speciation node are orthologs, and those that diverged at a duplication node are paralogs.”

    From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [20]

  • The species-overlap method identifies nodes as duplication nodes if the sets of species below its child nodes overlap; otherwise, the node is a speciation node.

    “In this method, nodes in the gene tree are identified as duplication nodes if the sets of species below its child nodes overlap; otherwise, the node is a speciation node.”

    From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [20]

    The Introduction distinguishes speciation from duplication, and ‘Single-Copy Orthologs in Eukaryotes’ mentions gene-tree reconciliation. Neither section states the claimed species-overlap rule for classifying child nodes; searches for that rule and its key terms found no passage addressing it. Page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. [1]Fitch WM Distinguishing homologous from analogous proteins Syst. Zool. 1970 19 99 113 5449325
  2. [2]Tatusov RL Koonin EV Lipman DJ A genomic perspective on protein families Science 1997 278 631 637 9381173
  3. [3]Gabaldón T Koonin EV Functional and evolutionary implications of gene orthology Nat. Rev. Genet. 2013 14 360 366 23552219 PMC5877793
  4. [4]Koonin EV Aravind L Kondrashov AS The impact of comparative genomics on our understanding of evolution Cell 2000 101 573 576 10892642
  5. [5]Tordai H Nagy A Farkas K Bányai L Patthy L Modules, multidomain proteins and organismic complexity FEBS J. 2005 272 5064 5078 16176277
  6. [6]Dalquen DA Altenhoff AM Gonnet GH Dessimoz C The impact of gene duplication, insertion, deletion, lateral gene transfer and sequencing error on orthology inference: a simulation study PloS One 2013 8 e56925 23451112 PMC3581572
  7. [7]Muller J Szklarczyk D Julien P Letunic I Roth A Kuhn M Powell S von Mering C Doerks T Jensen LJ eggNOG v2.0: extending the evolutionary genealogy of genes with enhanced non-supervised orthologous groups, species and functional annotations Nucleic Acids Res. 2010 38 D190 D195 19900971 PMC2808932
  8. [8]Jensen LJ Julien P Kuhn M von Mering C Muller J Doerks T Bork P eggNOG: automated construction and annotation of orthologous groups of genes Nucleic Acids Res. 2008 36 D250 D254 17942413 PMC2238944
  9. [9]Milinkovitch MC Helaers R Depiereux E Tzika AC Gabaldón T 2x genomes—depth does matter Genome Biol. 2010 11 R16 20144222 PMC2872876
  10. [10]Boeckmann B Robinson-Rechavi M Xenarios I Dessimoz C Conceptual framework and pilot study to benchmark phylogenomic databases based on reference gene trees Brief. Bioinform. 2011 12 423 435 21737420 PMC3178055
  11. [11]Trachana K Larsson TA Powell S Chen W-H Doerks T Muller J Bork P Orthology prediction methods: a quality assessment using curated protein families BioEssays 2011 33 769 780 21853451 PMC3193375
  12. [12]Hulsen T Huynen MA de Vlieg J Groenen PMA Benchmarking ortholog identification methods using functional genomics data Genome Biol. 2006 7 R31 16613613 PMC1557999
  13. [13]Chen F Mackey AJ Vermunt JK Roos DS Assessing performance of orthology detection strategies applied to eukaryotic genomes PloS One 2007 2 e383 17440619 PMC1849888
  14. [14]Altenhoff AM Dessimoz C Phylogenetic and functional assessment of orthologs inference projects and methods PLoS Comput. Biol. 2009 5 e1000262 19148271 PMC2612752
  15. [15]Salichos L Rokas A Evaluating ortholog prediction algorithms in a yeast model clade PLoS One 2011 6 e18755 21533202 PMC3076445
  16. [16]Tatusov RL Fedorova ND Jackson JD Jacobs AR Kiryutin B Koonin EV Krylov DM Mazumder R Mekhedov SL Nikolskaya AN The COG database: an updated version includes eukaryotes BMC Bioinform. 2003 4 41 PMC222959 12969510
  17. [17]Makarova KS Sorokin AV Novichkov PS Wolf YI Koonin EV Clusters of orthologous genes for 41 archaeal genomes and implications for evolutionary genomics of archaea Biol. Direct 2007 2 33 18042280 PMC2222616
  18. [18]Nakaya A Katayama T Itoh M Hiranuka K Kawashima S Moriya Y Okuda S Tanaka M Tokimatsu T Yamanishi Y KEGG OC: a large-scale automatic construction of taxonomy-based ortholog clusters Nucleic Acids Res. 2013 41 D353 D357 23193276 PMC3531156
  19. [19]Alkan C Sajjadian S Eichler EE Limitations of next-generation genome sequence assembly Nat. Methods 2011 8 61 65 21102452 PMC3115693
  20. [20]Szklarczyk D Franceschini A Kuhn M Simonovic M Roth A Minguez P Doerks T Stark M Muller J Bork P The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored Nucleic Acids Res. 2011 39 D561 D568 21045058 PMC3013807
  21. [21]Powell S Szklarczyk D Trachana K Roth A Kuhn M Muller J Arnold R Rattei T Letunic I Doerks T eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges Nucleic Acids Res. 2012 40 D284 D289 22096231 PMC3245133
  22. [22]Pruitt KD Tatusova T Maglott DR NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins Nucleic Acids Res. 2007 35 D61 D65 17130148 PMC1716718
  23. [23]Flicek P Amode MR Barrell D Beal K Brent S Carvalho-Silva D Clapham P Coates G Fairley S Fitzgerald S Ensembl 2012 Nucleic Acids Res. 2012 40 D84 D90 22086963 PMC3245178
  24. [24]UniProt Consortium Update on activities at the Universal Protein Resource (UniProt) in 2013 Nucleic Acids Res. 2013 41 D43 D47 23161681 PMC3531094
  25. [25]Aurrecoechea C Brestelli J Brunk BP Carlton JM Dommer J Fischer S Gajria B Gao X Gingle A Grant G GiardiaDB and TrichDB: integrated genomic resources for the eukaryotic protist pathogens Giardia lamblia and Trichomonas vaginalis Nucleic Acids Res. 2009 37 D526 D530 18824479 PMC2686445
  26. [26]Lamesch P Berardini TZ Li D Swarbreck D Wilks C Sasidharan R Muller R Dreher K Alexander DL Garcia-Hernandez M The Arabidopsis Information Resource (TAIR): improved gene annotation and new tools Nucleic Acids Res. 2012 40 D1202 D1210 22140109 PMC3245047
  27. [27]Stark M Berger SA Stamatakis A von Mering C MLTreeMap—accurate Maximum Likelihood placement of environmental DNA sequences into taxonomic and functional reference phylogenies BMC Genomics 2010 11 461 20687950 PMC3091657
  28. [28]Ciccarelli FD Doerks T von Mering C Creevey CJ Snel B Bork P Toward automatic reconstruction of a highly resolved tree of life Science 2006 311 1283 1287 16513982
  29. [29]Mende DR Sunagawa S Zeller G Bork P Accurate and universal delineation of prokaryotic species Nat. Methods 2013 10 881 884 23892899
  30. [30]Sunagawa S Mende DR Zeller G Izquierdo-Carrasco F Berger SA Kultima JR Coelho LP Arumugam M Tap J Nielsen HB Metagenomic species profiling using universal phylogenetic marker genes Nat. methods 2013 10 1196 1199 24141494
  31. [31]Duarte JM Wall PK Edger PP Landherr LL Ma H Pires JC Leebens-Mack J dePamphilis CW Identification of shared single copy nuclear genes in Arabidopsis, Populus, Vitis and Oryza and their phylogenetic utility across various taxonomic levels BMC Evol. Biol. 2010 10 61 20181251 PMC2848037
  32. [32]Lee YS Oh J Kim YU Kim N Yang S Hwang UW Mitome: dynamic and interactive database for comparative mitochondrial genomics in metazoan animals Nucleic Acids Res. 2008 36 D938 D942 17940090 PMC2238945
  33. [33]Van Bel M Proost S Wischnitzki E Movahedi S Scheerlinck C Van de Peer Y Vandepoele K Dissecting plant genomes with the PLAZA comparative genomics platform Plant Physiol. 2012 158 590 600 22198273 PMC3271752
  34. [35]Schloissnig S Arumugam M Sunagawa S Mitreva M Tap J Zhu A Waller A Mende DR Kultima JR Martin J Genomic variation landscape of the human gut microbiome Nature 2013 493 45 50 23222524 PMC3536929
  35. [36]Sorek R Zhu Y Creevey CJ Francino MP Bork P Rubin EM Genome-wide experimental determination of barriers to horizontal gene transfer Science 2007 318 1449 1452 17947550
  36. [37]Rattei T Tischler P Götz S Jehl MA Hoser J Arnold R Conesa A Mewes HW SIMAP–a comprehensive database of pre-calculated protein sequence similarities, domains, annotations and clusters Nucleic Acids Res. 2010 38 D223 D226 19906725 PMC2808863
  37. [38]Pearson WR Rapid and sensitive sequence comparison with FASTP and FASTA Methods Enzymol. 1990 183 63 98 2156132
  38. [40]Shpaer EG Robinson M Yee D Candlin JD Mines R Hunkapiller T Sensitivity and selectivity in protein similarity searches: a comparison of Smith-Waterman in hardware to BLAST and FASTA Genomics 1996 38 179 191 8954800
  39. [41]Wootton JC Federhen S Analysis of compositionally biased regions in sequence databases Methods Enzymol. 1996 266 554 571 8743706
  40. [42]Forslund K Sonnhammer ELL Benchmarking homology detection procedures with low complexity filters Bioinformatics 2009 25 2500 2505 19620098
  41. [43]Altschul SF Wootton JC Gertz EM Agarwala R Morgulis A Schäffer AA Yu YK Protein database searches using compositionally adjusted substitution matrices FEBS J. 2005 272 5101 5109 16218944 PMC1343503
  42. [44]Wolf YI Makarova KS Yutin N Koonin EV Updated clusters of orthologous genes for Archaea: a complex ancestor of the Archaea and the byways of horizontal gene transfer Biol. Direct 2012 7 46 23241446 PMC3534625
  43. [45]Tanabe M Kanehisa M Using the KEGG database resource Curr. Protoc. Bioinformatics 2012 Chapter 1, Unit1.12 22700311
  44. [46]Letunic I Doerks T Bork P SMART 7: recent updates to the protein domain annotation resource Nucleic Acids Res. 2012 40 D302 D305 22053084 PMC3245027
  45. [47]Punta M Coggill PC Eberhardt RY Mistry J Tate J Boursnell C Pang N Forslund K Ceric G Clements J The Pfam protein families database Nucleic Acids Res. 2012 40 D290 D301 22127870 PMC3245129
  46. [49]Koonin EV Orthologs, paralogs, and evolutionary genomics Annu. Rev. Genet. 2005 39 309 338 16285863
  47. [50]Eddy SR Mitchison G Durbin R Maximum discrimination hidden Markov models of sequence consensus J. Comput. Biol. 1995 2 9 23 7497123
  48. [51]Eddy SR A new generation of homology search tools based on probabilistic inference Genome Inform. 2009 23 205 211 20180275
  49. [53]Benson DA Karsch-Mizrachi I Lipman DJ Ostell J Sayers EW GenBank Nucleic Acids Res. 2009 37 D26 D31 18940867 PMC2686462
  50. [54]Sayers EW Barrett T Benson DA Bryant SH Canese K Chetvernin V Church DM DiCuccio M Edgar R Federhen S Database resources of the National Center for Biotechnology Information Nucleic Acids Res. 2009 37 D5 D15 18940862 PMC2686545
  51. [55]Gogarten JP Olendzenski L Orthologs, paralogs and genome comparisons Curr. Opin. Dev. 1999 9 630 636 10607614
  52. [56]Delsuc F Brinkmann H Philippe H Phylogenomics and the reconstruction of the tree of life Nat. Rev. Genet. 2005 6 361 375 15861208
  53. [58]Parra G Bradnam K Korf I CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes Bioinformatics 2007 23 1061 1067 17332020
  54. [59]Altenhoff AM Schneider A Gonnet GH Dessimoz C OMA 2011: orthology inference among 1000 complete genomes Nucleic Acids Res. 2011 39 D289 D294 21113020 PMC3013747
  55. [60]Creevey CJ Muller J Doerks T Thompson JD Arendt D Bork P Identifying single copy orthologs in Metazoa PLoS Comput. Biol. 2011 7 e1002269 22144877 PMC3228760
  56. [61]Huerta-Cepas J Capella-Gutierrez S Pryszcz LP Denisov I Kormes D Marcet-Houben M Gabaldón T PhylomeDB v3.0: an expanding repository of genome-wide collections of trees, alignments and phylogeny-based orthology and paralogy predictions Nucleic Acids Res. 2011 39 D556 D560 21075798 PMC3013701
  57. [63]Edgar RC MUSCLE: a multiple sequence alignment method with reduced time and space complexity BMC Bioinformatics 2004 5 113 15318951 PMC517706
  58. [64]Wallace IM O’Sullivan O Higgins DG Notredame C M-Coffee: combining multiple sequence alignment methods with T-Coffee Nucleic Acids Res. 2006 34 1692 1699 16556910 PMC1410914
  59. [65]Capella-Gutiérrez S Silla-Martínez JM Gabaldón T trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses Bioinformatics 2009 25 1972 1973 19505945 PMC2712344
  60. [66]Sievers F Wilm A Dineen D Gibson TJ Karplus K Li W Lopez R McWilliam H Remmert M Söding J Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega Mol. Syst. Biol. 2011 7 539 21988835 PMC3261699
  61. [67]Waterhouse AM Procter JB Martin DMA Clamp M Barton GJ Jalview Version 2–a multiple sequence alignment editor and analysis workbench Bioinformatics 2009 25 1189 1191 19151095 PMC2672624
  62. [68]Letunic I Bork P Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy Nucleic Acids Res. 2011 39 W475 W478 21470960 PMC3125724
  63. [69]Schmitt T Messina DN Schreiber F Sonnhammer ELL Letter to the editor: SeqXML and OrthoXML: standards for sequence and orthology information Brief. Bioinform. 2011 12 485 488 21666252
  64. [70]Sizova MV Hohmann T Hazen A Paster BJ Halem SR Murphy CM Panikov NS Epstein SS New approaches for isolation of previously uncultivated oral bacteria Appl. Environ. Microbiol. 2012 78 194 203 22057871 PMC3255620

Cited by

Sorted by citations

Authors
Powell, S., Forslund, K., Szklarczyk, D., Trachana, K., Roth, A., Huerta-Cepas, J., Gabaldón, T., Rattei, T., Creevey, C., Kuhn, M., Jensen, L. J., von Mering, C., & Bork, P.
Affiliations
  • SIB Swiss Institute of Bioinformatics (CH)
  • University of Copenhagen (DK)
Corresponding author
Jensen, Lars J.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2013-12-01
Volume
42
Issue
D1
Pages
D231-D239
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkt1253
PMC
PMC3964997
OpenAlex
W1997272729
Cited by
652
References
6
Citations by year
2026: 37 · 2025: 43 · 2024: 67 · 2023: 59 · 2022: 30 · 2021: 58 · 2020: 49 · 2019: 40 · 2018: 39 · 2017: 52 · 2016: 74 · 2015: 71 · 2014: 32
FWCI
22.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • reroDoc Digital Library (submittedVersion)
  • Phaidra (Universität Wien) (submittedVersion, cc-by-nc-nd)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Alexander von Humboldt-Stiftung
  • Novo Nordisk
  • Biotechnology and Biological Sciences Research Council (BBS/E/W/10964A01A)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
eggNOG, orthogroups, gene family annotation, genome completeness, taxonomic levels, multiple sequence alignment, phylogenetic tree construction, functional annotation, gene family clustering, quality control
MeSH terms
Multigene Family, Phylogeny, Proteins, Genome, Sequence Homology, Amino Acid, Internet, Genomics, Databases, Genetic, Molecular Sequence Annotation, Genome, Microbial

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review