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Standardized benchmarking in the quest for orthologs

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Quest for Orthologs consortium, Altenhoff, Adrian M, Boeckmann, Brigitte, Capella-Gutierrez, Salvador, Dalquen, Daniel A, DeLuca, Todd, Forslund, Kristoffer, Huerta-Cepas, Jaime +20 more·2016·Nature Methods
DOI 10.1038/nmeth.3830PMC PMC4827703
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Abstract

Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.

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  • QfO is the most widely used orthology benchmarking service, evaluating a tool's ability to accurately predict orthologs across diverse taxa.

    “QfO is the most widely used orthology benchmarking service, which evaluates a tool’s ability to accurately predict orthologs across a diverse set of taxa, including Archaea, Bacteria and eukaryotes.”

    From OrthoFinder: improved phylogenetic orthology inference with enhanced accuracy and scalability (2026) · cites this paper as [3]

    The Results (Benchmark service; page not provided) describe a QfO-based service that evaluates orthology predictions, and the Methods (Quest for orthologs reference proteomes and species tree; page not provided) specify a data set of 40 eukaryotes and 26 bacteria–archaea. The Discussion reports over a hundred prediction sets submitted, but does not establish that QfO is the most widely used orthology benchmarking service. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Comparative analyses have found no significant difference in ortholog detection accuracy between tree-based online databases and score-based software tools.

    “Comparative analyses of these methods using standard benchmarking approaches have found no significant difference in ortholog detection accuracy of these online databases and score-based software tools [1], suggesting that the advantages of a phylogenetic approach have not yet been fully realized.”

    From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [1]

    The Results (Generalized species tree discordance test; page not provided) report no obvious systematic performance difference between tree-based and graph-based methods. That supports the broad comparison, but the paper does not report a statistical finding of no significant difference, and its categories are not specifically online databases versus score-based software tools. The Discussion also describes performance as a precision–recall trade-off rather than a single measure of detection accuracy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • OrthoFinder orthologs using default options and multiple different configurations were submitted to the community-supported Quest for Orthologs benchmarking server for the 2011_04 dataset.

    “To demonstrate the accuracy of the overall method, the orthologs identified by OrthoFinder using its default options, along with multiple different configurations, were submitted to the community-supported Quest for Orthologs benchmarking server for the 2011_04 dataset [1] (see the “Methods” section for details of the tests).”

    From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [1]

  • The default options for OrthoFinder are recommended by the authors as they are fast and achieve high accuracy on the Quest for Orthologs benchmarks.

    “The default options are recommended by the authors as they are fast and achieve high accuracy on the Quest for Orthologs benchmarks [1] (Fig. 4a–d).”

    From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [1]

    The Results (Benchmark service; page unavailable) describe the Quest for Orthologs benchmarks, but the retrieved passages do not report OrthoFinder results. Searches for OrthoFinder, its default options, speed, and accuracy found no passage recommending those options or assessing their performance. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Quest for Orthologs consortium, Altenhoff, A. M., Boeckmann, B., Capella-Gutierrez, S., Dalquen, D. A., DeLuca, T., Forslund, K., Huerta-Cepas, J., Linard, B., Pereira, C., Pryszcz, L. P., Schreiber, F., da Silva, A. S., Szklarczyk, D., Train, C.-M., Bork, P., Lecompte, O., von Mering, C., Xenarios, I., Sjölander, K., Jensen, L. J., Martin, M. J., Muffato, M., Gabaldón, T., Lewis, S. E., Thomas, P. D., Sonnhammer, E., & Dessimoz, C.
Affiliations
  • SIB Swiss Institute of Bioinformatics (CH)
  • University College London (GB)
  • Harvard University (US)
  • Natural History Museum (GB)
  • Université Paris-Sud (FR)
  • Barcelona Institute of Science and Technology (ES)
  • European Bioinformatics Institute (GB)
  • ETH Zurich (CH)
  • Laboratoire des Sciences de l'Ingénieur, de l'Informatique et de l'Imagerie (FR)
  • University of California, Berkeley (US)
  • University of Copenhagen (DK)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • Lawrence Berkeley National Laboratory (US)
  • University of Southern California (US)
  • Stockholm University (SE)
Corresponding author
Dessimoz, Christophe
ORCID
Venue
Nature Methods
Publisher
Springer Science and Business Media LLC
Published
2016-04-04
Volume
13
Issue
5
Pages
425-430
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
DOI
10.1038/nmeth.3830
PMC
PMC4827703
OpenAlex
W2316262244
Cited by
214
References
1
Citations by year
2026: 8 · 2025: 18 · 2024: 12 · 2023: 16 · 2022: 15 · 2021: 24 · 2020: 33 · 2019: 25 · 2018: 33 · 2017: 22 · 2016: 7 · 2015: 1
FWCI
12.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Methods (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-sa)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by-nc-sa)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by-nc-sa)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • IRIS (submittedVersion, cc-by-nc-sa)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • HAL (submittedVersion, cc-by-nc-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by-nc-sa)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation (1355632, DEAC02-05CH11231)
  • U.S. Department of Energy (-AC02-05CH11231, Contract No. DE-AC02-05-CH11231, 05CH11231, No. DE-AC02-05-CH11231, DE AC02 05CH11231, DE-AC02-)
  • Wellcome Trust (WT095908)
  • European Molecular Biology Laboratory
  • Agence Nationale de la Recherche (ANR-10-BINF-0003, DE-AC02-05CH11231, ANR-10-BINF-03-02, ANR-10)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (150654, 37161)
  • Fonds National de la Recherche Luxembourg
  • Ministerio de Economía y Competitividad (DE AC02-05CH11231, BIO2012-37161)
  • Novo Nordisk (NNF14CC0001)
  • Novo Nordisk Fonden (NNF 14CC0001)
  • National Institutes of Health (R24OD011883, DE-AC02–05CH11231, HG007822, HG002273)
  • Directorate for Biological Sciences
  • Qatar National Research Fund (5-298-3-086, NPRP 5‐298‐3‐086)
  • Biotechnology and Biological Sciences Research Council (BB/L018241/1)
  • Staatssekretariat für Bildung, Forschung und Innovation
  • National Human Genome Research Institute (U41HG002273, U41HG007822)
  • Basic Energy Sciences (DE-AC02, Contract No. DE-AC02-05-CH11231, DE-AC02-05CH11231., No. DE-AC02-05-CH11231, AC02–05CH11231)
  • Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, No. DE-AC02-05CH11231, Contract No. DE-AC02-05CH11231, 05CH11231)
  • FP7 Ideas: European Research Council (310325)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
Keywords
orthology inference, orthologs, benchmarking, standardized assessment, precision-recall trade-off, comparative genomics
MeSH terms
Archaea, Bacteria, Models, Genetic, Phylogeny, Species Specificity, Sequence Homology, Computational Biology, Sequence Analysis, Protein, Genomics, Databases, Genetic, Proteomics, Eukaryota, Gene Ontology

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