ArticleProceedings of the National Academy of Sciences of the United States of America2023
Improved global protein homolog detection with major gains in function identification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- The Advantages of AI for Computational Protein Studies and Looking Ahead at the Next Challenges: Single Structures Are Not Enough.Journal of molecular biology · 2026Review
- Benchmarking protein sequence and structure search methods for remote homology detection.Genome biology · 2026Article
- Lineage-specific elaboration of a conserved cnidogenic program drives cnidocyte diversification and illuminates cell type evolution.Research square · 2026Article
- Structural genomics sheds light on protein functions and remote homologs across the insect tree of life.Cell research · 2026Article
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- Identification of a highly expressed gene cluster likely coding for benzene activation enzymes in a methanogenic enrichment culture.Applied and environmental microbiology · 2026Article
- Machine learning-assisted multi-aptamer encoding enables pattern-level discrimination of HbA1c in complex biological matrices.Mikrochimica acta · 2026Article
- Large Numbers of New Human Paralogs Discovered.bioRxiv : the preprint server for biology · 2025Article
- Article
- Medium-sized protein language models perform well at transfer learning on realistic datasets.Scientific reports · 2025Article
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Medium-sized protein language models perform well at transfer learning on realistic datasets.bioRxiv : the preprint server for biology · 2025Article
- Article
- A fast approach for structural and evolutionary analysis based on energetic profile protein comparison.Nature communications · 2025Article
- The neuropeptidomes of the sea cucumbers Stichopus cf. horrens and Holothuria scabra.Scientific reports · 2025Article
- Major advances in protein function assignment by remote homolog detection with protein language models - A review.Current opinion in structural biology · 2025Review
- A Novel Membrane-Associated Protein Aids Bacterial Colonization of Maize.ACS synthetic biology · 2025Article
- CATHe2: Enhanced CATH superfamily detection using ProstT5 and structural alphabets.Biology methods & protocols · 2025Article
- Improving the Annotations of JCVI-Syn3a Proteins.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Expanding the β-Lactamase Family in the Human Microbiome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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3 authors.
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Abstract
There are several hundred million protein sequences, but the relationships among them are not fully available from existing homolog detection methods. There is an essential need for an improved method to push homolog detection to lower levels of sequence identity. The method used here relies on a language model to represent proteins numerically in a matrix (an embedding) and uses discrete cosine transforms to compress the data to extract the most essential part, significantly reducing the data size. This PRotein Ortholog Search Tool (PROST) is significantly faster with linear runtimes, and most importantly, computes the distances between pairs of protein sequences to yield homologs at significantly lower levels of sequence identity than previously. The extent of allosteric effects in proteins points out the importance of global aspects of structure and sequence. PROST excels at global homology detection but not at detecting local homologs. Results are validated by strong similarities between the corresponding pairs of structures. The number of remote homologs detected increased significantly and pushes the effective sequence matches more deeply into the twilight zone. Human protein sequences presently having no assigned function now find significant numbers of putative homologs for 93% of cases and structurally verified assigned functions for 76.4% of these cases. The data compression enables massive searches for homologs with short search times while yielding significant gains in the numbers of remote homologs detected. The method is sufficiently efficient to permit whole-genome/proteome comparisons. The PROST web server is accessible at https://mesihk.github.io/prost.
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