Orthology prediction methods: A quality assessment using curated protein families
Open accessAbstract
The increasing number of sequenced genomes has prompted the development of several automated orthology prediction methods. Tests to evaluate the accuracy of predictions and to explore biases caused by biological and technical factors are therefore required. We used 70 manually curated families to analyze the performance of five public methods in Metazoa. We analyzed the strengths and weaknesses of the methods and quantified the impact of biological and technical challenges. From the latter part of the analysis, genome annotation emerged as the largest single influencer, affecting up to 30% of the performance. Generally, most methods did well in assigning orthologous group but they failed to assign the exact number of genes for half of the groups. The publicly available benchmark set (http://eggnog.embl.de/orthobench/) should facilitate the improvement of current orthology assignment protocols, which is of utmost importance for many fields of biology and should be tackled by a broad scientific community.
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Gene annotation quality has a large influence on the accuracy of orthology inference.
“First, gene annotation quality has a large influence on the accuracy of orthology inference (15).”
From Integrating gene annotation with orthology inference at scale (2023) · cites this paper as [15]
The OrthoBench dataset consists of expert-curated reference orthogroups.
“we compared this new version of OrthoFinder with a set of alternative methods on the OrthoBench dataset of expert-curated reference orthogroups20,21.”
From OrthoFinder: improved phylogenetic orthology inference with enhanced accuracy and scalability (2026) · cites this paper as [20]
Orthogroup inference accuracy of OrthoFinder has already been tested using the independent Orthobench dataset, and it was the most accurate method tested in terms of overall F-score.
“Orthogroup inference accuracy of OrthoFinder has already been tested using the independent Orthobench dataset [11]. This showed to be the most accurate method tested in terms of overall F-score (although other methods scored higher in terms of either precision or recall while scoring proportionally worse in the other) [10].”
From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [11]
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Cites
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Sorted by citations
OrthoFinder: phylogenetic orthology inference for comparative genomics
Emms, D. M., & Kelly, S. (2019) · Genome Biology · doi:10.1186/s13059-019-1832-y · Cited by 7,676 · see citing works
Integrating gene annotation with orthology inference at scale
Kirilenko, B. M., Munegowda, C., Osipova, E., Jebb, D., Sharma, V., Blumer, M., Morales, A. E., Ahmed, A.-W., Kontopoulos, D.-G., Hilgers, L., et al. (2023) · Science · doi:10.1126/science.abn3107 · Cited by 209 · see citing works
OrthoFinder: improved phylogenetic orthology inference with enhanced accuracy and scalability
Emms, D. M., Liu, Y., Belcher, L., Holmes, J., & Kelly, S. (2026) · Nature Methods · doi:10.1038/s41592-026-03126-6 · Cited by 25 · see citing works
- Authors
- Trachana, K., Larsson, T. A., Powell, S., Chen, W., Doerks, T., Muller, J., & Bork, P.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Centre National de la Recherche Scientifique (FR)
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2011-08-19
- Volume
- 33
- Issue
- 10
- Pages
- 769-780
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- PMC
- PMC3193375
- OpenAlex
- W2030317329
- Cited by
- 139
- References
- 5
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 11 · 2020: 10 · 2019: 19 · 2018: 9 · 2017: 13 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 12 · 2012: 8
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BioEssays (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- 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
- orthology prediction, protein families, orthogroups, benchmarking, animals, automatic annotation
- MeSH terms
- Algorithms, Animals, Genes, Mucins, Phylogeny, Proteins, Species Specificity, User-Computer Interface, Reproducibility of Results, Computational Biology, Internet, Databases, Genetic, Databases, Protein, Molecular Sequence Annotation
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