ArticleBioinformatics (Oxford, England)2020
The ortholog conjecture revisited: the value of orthologs and paralogs in function prediction.
Article in Bioinformatics (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 71 citations in OpenAlex.
- Iterative and data-driven ortholog mining enables reliable discovery of stereoselective ketoreductases.Nature communications · 2026Article
- Computational strategies for cross-species knowledge transfer.Nature methods · 2026Review
- De novo discovery of conserved gene clusters in microbial genomes with Spacedust.Nature methods · 2025Article
- Comprehensive analysis of orthologous genes reveals functional dynamics and energy metabolism in the rhizospheric microbiome of Moringa oleifera.Functional & integrative genomics · 2025Article
- Species Identification and Orthologous Allergen Prediction and Expression in the GenusJournal of fungi (Basel, Switzerland) · 2025Article
- A metric and its derived protein network for evaluation of ortholog database inconsistency.BMC bioinformatics · 2025Article
- Evolutionary dynamics of the calcium/cation antiporter superfamily in Brassicaceae: codon usage, selection pressure, andFrontiers in plant science · 2025Article
- Quest for Orthologs in the Era of Biodiversity Genomics.Genome biology and evolution · 2024Review
- Computational strategies for cross-species knowledge transfer and translational biomedicine.ArXiv · 2024Article
- A Novel Approach to Comparative RNA-Seq Does Not Support a Conserved Set of Orthologs Underlying Animal Regeneration.Genome biology and evolution · 2024Article
- Macroevolutionary dynamics of gene family gain and loss along multicellular eukaryotic lineages.Nature communications · 2024Article
- Contingency, repeatability, and predictability in the evolution of a prokaryotic pangenome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Approaches to increase the validity of gene family identification using manual homology search tools.Genetica · 2023Review
- Benchmarking strategies for cross-species integration of single-cell RNA sequencing data.Nature communications · 2023Article
- Estimating transcriptome complexities across eukaryotes.BMC genomics · 2023Article
- Theme and variation in the evolution of insect sex determination.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023Review
- Real or fake? Measuring the impact of protein annotation errors on estimates of domain gain and loss events.Frontiers in bioinformatics · 2023Article
- Article
- Paralogous Genes Involved in Embryonic Development: Lessons from the Eye and Other Tissues.Genes · 2022Review
- Genome-Wide Classification and Phylogenetic Analyses of the GDSL-Type Esterase/Lipase (GELP) Family in Flowering Plants.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
motivationThe computational prediction of gene function is a key step in making full use of newly sequenced genomes. Function is generally predicted by transferring annotations from homologous genes or proteins for which experimental evidence exists. The 'ortholog conjecture' proposes that orthologous genes should be preferred when making such predictions, as they evolve functions more slowly than paralogous genes. Previous research has provided little support for the ortholog conjecture, though the incomplete nature of the data cast doubt on the conclusions.
resultsWe use experimental annotations from over 40 000 proteins, drawn from over 80 000 publications, to revisit the ortholog conjecture in two pairs of species: (i) Homo sapiens and Mus musculus and (ii) Saccharomyces cerevisiae and Schizosaccharomyces pombe. By making a distinction between questions about the evolution of function versus questions about the prediction of function, we find strong evidence against the ortholog conjecture in the context of function prediction, though questions about the evolution of function remain difficult to address. In both pairs of species, we quantify the amount of information that would be ignored if paralogs are discarded, as well as the resulting loss in prediction accuracy. Taken as a whole, our results support the view that the types of homologs used for function transfer are largely irrelevant to the task of function prediction. Maximizing the amount of data used for this task, regardless of whether it comes from orthologs or paralogs, is most likely to lead to higher prediction accuracy. AVAILABILITY AND IMPLEMENTATION: https://github.com/predragradivojac/oc. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.