ArticleBioinformatics (Oxford, England)2024
Embedding-based alignment: combining protein language models with dynamic programming alignment to detect structural similarities in the twilight-zone.
Article in Bioinformatics (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 43 citations in OpenAlex.
- Systematic discovery of circular permutations across the protein universe using CIRPIN.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advances in Protein Function Prediction from the Fifth CAFA Challenge.bioRxiv : the preprint server for biology · 2026Article
- BABAPPAlign: a multiple sequence alignment engine with a learned residue-level scoring function.Bioinformatics (Oxford, England) · 2026Article
- Much ado about nothing: modeling amino acid replacement with predicted protein structures.Bioinformatics (Oxford, England) · 2026Article
- pLM-Repeat: Exploiting the sequence representations of protein language models for sensitive repeat detection.Protein science : a publication of the Protein Society · 2026Article
- Review
- Protein Structure Prediction Methods.Advances in experimental medicine and biology · 2026Review
- Alternative Conformation Prediction Using Deep Learning With Multi-MSA Strategy and Structural Clustering in CASP16.Proteins · 2026Article
- Protein embeddings and local alignments.Computational and structural biotechnology journal · 2026Article
- Beyond sequence similarity: toward function-based screening of nucleic acid synthesis.Frontiers in bioengineering and biotechnology · 2026Article
- DeepVIC: modular prediction and classification of bacterial virulence factors using protein language model embeddings.Bioinformatics advances · 2026Article
- Template-based RNA structure prediction advanced through a blind code competition.bioRxiv : the preprint server for biology · 2025Article
- Application and Prospects of Large Language Models in Small-Molecule Drug Discovery.Analytical chemistry · 2025Review
- CIRPIN: Learning Circular Permutation-Invariant Representations to Uncover Putative Protein Homologs.bioRxiv : the preprint server for biology · 2025Article
- Evaluating the significance of embedding-based protein sequence alignment with clustering and double dynamic programming for remote homology.Scientific reports · 2025Article
- DeepFold-PLM: accelerating protein structure prediction via efficient homology search using protein language models.Bioinformatics (Oxford, England) · 2025Article
- Evolutionary Reasoning Does Not Arise in Standard Usage of Protein Language Models.bioRxiv : the preprint server for biology · 2025Article
- Paying attention to attention: High attention sites as indicators of protein family and function in language models.PLoS computational biology · 2025Article
- Protein Structural Phylogenetics.Genome biology and evolution · 2025Review
- Cutting-edge deep-learning based tools for metagenomic research.National science review · 2025Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
motivationLanguage models are routinely used for text classification and generative tasks. Recently, the same architectures were applied to protein sequences, unlocking powerful new approaches in the bioinformatics field. Protein language models (pLMs) generate high-dimensional embeddings on a per-residue level and encode a "semantic meaning" of each individual amino acid in the context of the full protein sequence. These representations have been used as a starting point for downstream learning tasks and, more recently, for identifying distant homologous relationships between proteins.
resultsIn this work, we introduce a new method that generates embedding-based protein sequence alignments (EBA) and show how these capture structural similarities even in the twilight zone, outperforming both classical methods as well as other approaches based on pLMs. The method shows excellent accuracy despite the absence of training and parameter optimization. We demonstrate that the combination of pLMs with alignment methods is a valuable approach for the detection of relationships between proteins in the twilight-zone. AVAILABILITY AND IMPLEMENTATION: The code to run EBA and reproduce the analysis described in this article is available at: https://git.scicore.unibas.ch/schwede/EBA and https://git.scicore.unibas.ch/schwede/eba_benchmark.
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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.