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Cited by 45Genomics and Phylogenetic StudiesBioinformatics and Genomic NetworksChromosomal and Genetic Variations

Ten Years of Collaborative Progress in the Quest for Orthologs

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Linard, Benjamin, Ebersberger, Ingo, McGlynn, Shawn E, Glover, Natasha, Mochizuki, Tomohiro, Patricio, Mateus, Lecompte, Odile, Nevers, Yannis +50 more·2021·Molecular Biology and Evolution
DOI 10.1093/molbev/msab098PMC PMC8321534
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Abstract

Accurate determination of the evolutionary relationships between genes is a foundational challenge in biology. Homology—evolutionary relatedness—is in many cases readily determined based on sequence similarity analysis. By contrast, whether or not two genes directly descended from a common ancestor by a speciation event (orthologs) or duplication event (paralogs) is more challenging, yet provides critical information on the history of a gene. Since 2009, this task has been the focus of the Quest for Orthologs (QFO) Consortium. The sixth QFO meeting took place in Okazaki, Japan in conjunction with the 67th National Institute for Basic Biology conference. Here, we report recent advances, applications, and oncoming challenges that were discussed during the conference. Steady progress has been made toward standardization and scalability of new and existing tools. A feature of the conference was the presentation of a panel of accessible tools for phylogenetic profiling and several developments to bring orthology beyond the gene unit—from domains to networks. This meeting brought into light several challenges to come: leveraging orthology computations to get the most of the incoming avalanche of genomic data, integrating orthology from domain to biological network levels, building better gene models, and adapting orthology approaches to the broad evolutionary and genomic diversity recognized in different forms of life and viruses.

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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 [4]

    The Introduction describes a QFO online benchmarking service for assessing and comparing orthology inference methods, and the Scalability, Standardization, and Benchmarking section discusses its tests. Neither passage says it is the most widely used service or establishes that its benchmarks cover Archaea, Bacteria, and eukaryotes specifically. Page numbers are not available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Widespread genome sequencing efforts are creating an unprecedented scalability challenge for automated orthology inference methods.

    “These pioneering efforts, combined with widespread sequencing efforts that are distributed across many biological communities, are creating an unprecedented scalability challenge for automated orthology inference methods4,11.”

    From OrthoFinder: improved phylogenetic orthology inference with enhanced accuracy and scalability (2026) · cites this paper as [4]

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Cited by

Sorted by citations

Authors
Linard, B., Ebersberger, I., McGlynn, S. E., Glover, N., Mochizuki, T., Patricio, M., Lecompte, O., Nevers, Y., Thomas, P. D., Gabaldón, T., Sonnhammer, E., Dessimoz, C., Uchiyama, I., QFO Consortium, Altenhoff, A., Ouangraoua, A., Vesztrocy, A. W., Linard, B., Dessimoz, C., Szklarczyk, D., Durand, D., Emms, D., Moi, D., Thybert, D., Sonnhammer, E., Kriventseva, E., Tang, H., Chiba, H., Uchiyama, I., Ebersberger, I., Huerta-Cepas, J., Fernandez-Breis, J. T., Blake, J. A., Pryszcz, L., Martin, M.-J., Houben, M. M., Patricio, M., Muffato, M., Glover, N., Lecompte, O., Thomas, P. D., Schiffer, P., Capella-Gutierrez, S., Cosentino, S., McGlynn, S. E., Kuraku, S., Forslund, S., Kelly, S., Lewis, S., Jones, T., de Farias, T. M., Maeda, T., Gabaldon, T., Iwasaki, W., Pearson, W., Wang, Y., Nevers, Y., & Hara, Y.
Affiliations
  • Tokyo Institute of Technology (JP)
  • Barcelona Supercomputing Centre (BCS-CNS), Jordi Girona, Barcelona, Spain
  • Centre National de la Recherche Scientifique (FR)
  • Goethe University Frankfurt (DE)
  • LOEWE Centre for Translational Biodiversity Genomics (DE)
  • SIB Swiss Institute of Bioinformatics (CH)
ORCID
Venue
Molecular Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2021-04-02
Volume
38
Issue
8
Pages
3033-3045
ISSN
  • 0737-4038 (ISSN-L)
  • 1537-1719
DOI
10.1093/molbev/msab098
PMC
PMC8321534
OpenAlex
W3143333549
Cited by
45
References
5
Citations by year
2026: 4 · 2025: 8 · 2024: 14 · 2023: 10 · 2022: 7 · 2021: 2
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Biology and Evolution (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • IRIS (submittedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
  • UPCommons institutional repository (Universitat Politècnica de Catalunya) (submittedVersion, cc-by)
Funders
  • Swiss Institute of Bioinformatics
  • Swiss National Science Foundation (183723)
  • French government
  • NSF (1724300)
  • KAKENHI (JP18H01325)
  • Wellcome Trust (108749/Z/15/Z)
  • European Molecular Biology Laboratory
  • National Human Genome Research Institute
  • National Institutes of Health (U41HG002273)
  • National Science Foundation (1917302)
  • Japan Society for the Promotion of Science (16H06279, 19F19089)
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
ortholog identification, paralogs, gene duplication, homology, phylogenetic profiling, gene models, protein domains, biological networks, comparative genomics
MeSH terms
Phylogeny, Genome, Viral, Genomics, Genetic Speciation

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.

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