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Cited by 26Genomics and Phylogenetic StudiesBioinformatics and Genomic NetworksChromosomal and Genetic Variations

Quest for Orthologs in the Era of Biodiversity Genomics

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Langschied, Felix, Bordin, Nicola, Cosentino, Salvatore, Fuentes-Palacios, Diego, Glover, Natasha, Hiller, Michael, Hu, Yanhui, Huerta-Cepas, Jaime +11 more·2024·Genome Biology and Evolution
DOI 10.1093/gbe/evae224PMC PMC11523110
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Abstract

The era of biodiversity genomics is characterized by large-scale genome sequencing efforts that aim to represent each living taxon with an assembled genome. Generating knowledge from this wealth of data has not kept up with this pace. We here discuss major challenges to integrating these novel genomes into a comprehensive functional and evolutionary network spanning the tree of life. In summary, the expanding datasets create a need for scalable gene annotation methods. To trace gene function across species, new methods must seek to increase the resolution of ortholog analyses, e.g. by extending analyses to the protein domain level and by accounting for alternative splicing. Additionally, the scope of orthology prediction should be pushed beyond well-investigated proteomes. This demands the development of specialized methods for the identification of orthologs to short proteins and noncoding RNAs and for the functional characterization of novel gene families. Furthermore, protein structures predicted by machine learning are now readily available, but this new information is yet to be integrated with orthology-based analyses. Finally, an increasing focus should be placed on making orthology assignments adhere to the findable, accessible, interoperable, and reusable (FAIR) principles. This fosters green bioinformatics by avoiding redundant computations and helps integrating diverse scientific communities sharing the need for comparative genetics and genomics information. It should also help with communicating orthology-related concepts in a format that is accessible to the public, to counteract existing misinformation about evolution.

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  • 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 [11]

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Cited by

Sorted by citations

Authors
Langschied, F., Bordin, N., Cosentino, S., Fuentes-Palacios, D., Glover, N., Hiller, M., Hu, Y., Huerta-Cepas, J., Coelho, L. P., Iwasaki, W., Majidian, S., Manzano-Morales, S., Persson, E., Richards, T. A., Gabaldón, T., Sonnhammer, E., Thomas, P. D., Dessimoz, C., & Ebersberger, I.
Affiliations
  • Goethe University Frankfurt (DE)
  • Institute of Structural and Molecular Biology (GB)
  • The University of Tokyo (JP)
  • Barcelona Supercomputing Center (BSC-CNS) , 08034 Barcelona ,
  • SIB Swiss Institute of Bioinformatics (CH)
  • Harvard University (US)
  • Centro de Biotecnología y Genómica de Plantas, Universidad Politécnica de Madrid (UPM) - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Campus de Montegancedo-UPM , Madrid ,
  • Translational Research Institute (AU)
  • Barcelona Supercomputing Center (ES)
  • Stockholm University (SE)
  • University of Oxford (GB)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • University of Southern California (US)
Corresponding author
  • Langschied, Felix
  • Ebersberger, Ingo
ORCID
Venue
Genome Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2024-10
Volume
16
Issue
10
ISSN
1759-6653 (ISSN-L)
DOI
10.1093/gbe/evae224
PMC
PMC11523110
OpenAlex
W4403432206
Cited by
26
References
11
Citations by year
2026: 15 · 2025: 11
FWCI
1.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome Biology and Evolution (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Oxford University Research Archive (ORA) (University of Oxford) (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by)
  • IRIS (submittedVersion, cc-by)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
  • Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz
  • LOEWE
  • Translational Biodiversity Genomics
  • TBG
  • Swiss National Science Foundation (205085), 199775))
  • Swiss Institute of Bioinformatics
  • Royal Society University Research Fellowship (URF\R\191005)
  • Wellcome Trust (221327/Z/20/Z))
  • Swedish Research Council (2019-04095)
  • Ministry of Science and Innovation (PID2021-126067NB-I00, CPP2021-008552, PCI2022-135066-2, PDC2022-133266-I00)
  • Catalan Research Agency
  • AGAUR (SGR01551)
  • European Union's Horizon 2020 Research and Innovation Programme (ERC-2016-724173)
  • Gordon and Betty Moore Foundation (GBMF9742)
  • “La Caixa” foundation (LCF/PR/HR21/00737)
  • Instituto de Salud Carlos III (IMPACT Grant IMP/00019, CIBERINFEC CB21/13/00061-ISCIII-SGEFI/ERDF)
  • National Programme for Fostering Excellence in Scientific and Technical Research (MCIN/AEI/10.13039/501100011033/)
  • FEDER
  • Una manera de hacer Europa (PID2021-127210NB-I00)
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, biodiversity genomics, genome annotation, protein domains, alternative splicing, novel gene families, protein structure prediction, FAIR principles, comparative genomics, evolution education
MeSH terms
Animals, Evolution, Molecular, Computational Biology, Genomics, Biodiversity, Molecular Sequence Annotation

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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.

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