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Using deep learning to annotate the protein universe
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Abstract
Understanding the relationship between amino acid sequence and protein function is a long-standing challenge with far-reaching scientific and translational implications. State-of-the-art alignment-based techniques cannot predict function for one-third of microbial protein sequences, hampering our ability to exploit data from diverse organisms. Here, we train deep learning models to accurately predict functional annotations for unaligned amino acid sequences across rigorous benchmark assessments built from the 17,929 families of the protein families database Pfam. The models infer known patterns of evolutionary substitutions and learn representations that accurately cluster sequences from unseen families. Combining deep models with existing methods significantly improves remote homology detection, suggesting that the deep models learn complementary information. This approach extends the coverage of Pfam by >9.5%, exceeding additions made over the last decade, and predicts function for 360 human reference proteome proteins with no previous Pfam annotation. These results suggest that deep learning models will be a core component of future protein annotation tools.
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“These embeddings can capture evolutionary traits of the proteins, as well as functional and structural characteristics.119”
From Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence (2023) · cites this paper as [119]
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Metadata
- Authors
- Bileschi, M. L., Belanger, D., Bryant, D. H., Sanderson, T., Carter, B., Sculley, D., Bateman, A., DePristo, M. A., & Colwell, L. J.
- Affiliations
- Google (United States) (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- European Bioinformatics Institute (GB)
- Corresponding author
- Bileschi, Maxwell L.
- Colwell, Lucy J.
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2022-02-21
- Volume
- 40
- Issue
- 6
- Pages
- 932-937
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W4213112325
- Cited by
- 332
- References
- 59
- Citations by year
- 2026: 39 · 2025: 66 · 2024: 70 · 2023: 73 · 2022: 45
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Biotechnology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (210918/Z/18/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- 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
- Keywords
- protein function prediction, deep learning, Pfam, sequence annotation, remote homology detection, sequence clustering, microbial protein, human proteome, protein families
- MeSH terms
- Deep Learning, Amino Acid Sequence, Humans, Proteome, Databases, Protein, Proteomics, Molecular Sequence Annotation
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