OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy
Open accessAbstract
Identifying homology relationships between sequences is fundamental to biological research. Here we provide a novel orthogroup inference algorithm called OrthoFinder that solves a previously undetected gene length bias in orthogroup inference, resulting in significant improvements in accuracy. Using real benchmark datasets we demonstrate that OrthoFinder is more accurate than other orthogroup inference methods by between 8 % and 33 %. Furthermore, we demonstrate the utility of OrthoFinder by providing a complete classification of transcription factor gene families in plants revealing 6.9 million previously unobserved relationships.
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The original OrthoFinder orthogroup inference method is still the most accurate method on the independent Orthobench test set.
“The original OrthoFinder orthogroup inference method is still the most accurate method on the independent Orthobench test set [10] and thus is used for this step.”
From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [10]
The ‘OrthoFinder outperforms all other methods from the OrthoBench analysis’ section reports that OrthoFinder had the highest F-score among methods applied to OrthoBench, and the Evaluation section describes the dataset as independently evaluated. The 2015 paper does not establish that the original method is *still* the most accurate after that comparison. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn previous versions of OrthoFinder, orthogroups were defined solely based on MCL clustering of sequence similarity search results.
“In previous versions of OrthoFinder, orthologs were defined phylogenetically, whereas orthogroups were defined solely based on Markov Cluster Algorithm (MCL) clustering of sequence similarity search results12,16.”
From OrthoFinder: improved phylogenetic orthology inference with enhanced accuracy and scalability (2026) · cites this paper as [16]
The accuracy of key component algorithms of OrthoFinder has been independently assessed in this work and in dedicated publications.
“The accuracy of key component algorithms of OrthoFinder has been independently assessed in this work and in dedicated publications [5, 10, 22, 24, 33].”
From OrthoFinder: phylogenetic orthology inference for comparative genomics (2019) · cites this paper as [10]
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 [10]
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Self-citation
- Authors
- Emms, D. M., & Kelly, S.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Kelly, Steven
- Venue
- Genome Biology
- Published
- 2015-08-06
- Volume
- 16
- Issue
- 1
- Pages
- 157-157
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC4531804
- OpenAlex
- W1900937478
- Cited by
- 3,408
- References
- 3
- Citations by year
- 2026: 258 · 2025: 303 · 2024: 358 · 2023: 345 · 2022: 396 · 2021: 526 · 2020: 487 · 2019: 352 · 2018: 232 · 2017: 107 · 2016: 34 · 2015: 4 · 2014: 1
- FWCI
- 49.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (submittedVersion, cc-by)
- Funders
- Bill and Melinda Gates Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- OrthoFinder, whole-genome comparison, gene family classification, transcription factor gene family, plant genome, ortholog identification
- MeSH terms
- Algorithms, Multigene Family, Phylogeny, Proteins, Software, Transcription Factors, Genes, Plant, Genomics
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