Cross-phyla protein annotation by structural prediction and alignment
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Abstract
Background: Protein annotation is a major goal in molecular biology, yet experimentally determined knowledge is typically limited to a few model organisms. In non-model species, the sequence-based prediction of gene orthology can be used to infer protein identity; however, this approach loses predictive power at longer evolutionary distances. Here we propose a workflow for protein annotation using structural similarity, exploiting the fact that similar protein structures often reflect homology and are more conserved than protein sequences. Results: We propose a workflow of openly available tools for the functional annotation of proteins via structural similarity ( MorF : Mor pholog F inder) and use it to annotate the complete proteome of a sponge. Sponges are highly relevant for inferring the early history of animals, yet their proteomes remain sparsely annotated. MorF accurately predicts the functions of proteins with known homology in $${>}90\%$$ > 90 % cases and annotates an additional $$50\%$$ 50 % of the proteome beyond standard sequence-based methods. We uncover new functions for sponge cell types, including extensive FGF, TGF, and Ephrin signaling in sponge epithelia, and redox metabolism and control in myopeptidocytes. Notably, we also annotate genes specific to the enigmatic sponge mesocytes, proposing they function to digest cell walls. Conclusions: Our work demonstrates that structural similarity is a powerful approach that complements and extends sequence similarity searches to identify homologous proteins over long evolutionary distances. We anticipate this will be a powerful approach that boosts discovery in numerous -omics datasets, especially for non-model organisms.
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- Authors
- Ruperti, F., Papadopoulos, N., Musser, J. M., Mirdita, M., Steinegger, M., & Arendt, D.
- Affiliations
- Heidelberg University (DE)
- European Molecular Biology Laboratory (DE)
- Seoul National University (KR)
- Corresponding author
- Arendt, Detlev
- Venue
- Genome Biology
- Published
- 2023-05-12
- Volume
- 24
- Issue
- 1
- Pages
- 113-113
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC10176882
- OpenAlex
- W4376278240
- Cited by
- 38
- References
- 11
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 15 · 2023: 2 · 2022: 4
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-02-19)
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- H2020 Marie Skłodowska-Curie Actions (101031984/DeCoDe Platy, No. 764840/IGNITE)
- National Research Foundation of Korea (2020M3-A9G7-103933, 2021-R1C1-C102065, 2021-M3A9-I4021220)
- H2020 European Research Council (788921/NeuralCellTypeEvo)
- European Molecular Biology Laboratory (EMBL)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- protein annotation, structural similarity, non-model organisms, MORF, protein structure prediction, protein sequence alignment, FGF signaling, TGF signaling, ephrin signaling, redox metabolism, cell wall digestion, early animal evolution
- MeSH terms
- Amino Acid Sequence, Animals, Proteome, Molecular Sequence Annotation
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