Deep embedding and alignment of protein sequences
Open accessPublished version of a preprint
Abstract
Abstract Protein sequence alignment is a key component of most bioinformatics pipelines to study the structures and functions of proteins. Aligning highly divergent sequences remains, however, a difficult task that current algorithms often fail to perform accurately, leaving many proteins or open reading frames poorly annotated. Here, we leverage recent advances in deep learning for language modelling and differentiable programming to propose DEDAL, a flexible model to align protein sequences and detect homologs. DEDAL is a machine learning-based model that learns to align sequences by observing large datasets of raw protein sequences and of correct alignments. Once trained, we show that DEDAL improves by up to two- or three-fold the alignment correctness over existing methods on remote homologs, and better discriminates remote homologs from evolutionarily unrelated sequences, paving the way to improvements on many downstream tasks relying on sequence alignment in structural and functional genomics.
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- Authors
- Llinares-López, F., Berthet, Q., Blondel, M., Teboul, O., & Vert, J.-P.
- Affiliations
- Google (United States) (US)
- Corresponding author
- Vert, Jean-Philippe
- Venue
- Nature Methods
- Published
- 2022-12-15
- Volume
- 20
- Issue
- 1
- Pages
- 104-111
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W4311661986
- Cited by
- 58
- References
- 7
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 19 · 2023: 5 · 2022: 5
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Methods (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- protein sequence alignment, deep learning, differentiable programming, homology detection, divergent sequences, protein structure annotation, open reading frames
- MeSH terms
- Algorithms, Amino Acid Sequence, Proteins, Sequence Alignment, Genomics
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