ArticleProteomes2026
Protein Language Model Embeddings Reveal Proteome-Scale Ortholog Divergence Relevant to Cross-Species Pharmacology.
Article in Proteomes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundComparative proteome analysis can reveal functional conservation and divergence among orthologous proteins, with important implications for pharmacology and toxicology. Protein language models (PLMs) may capture sequence-derived functional relationships beyond what conventional alignment metrics capture.
methodsOrthologous proteins from
resultsOrtholog pairs showed strong global conservation, with a median PLM distance of 0.000487, whereas randomized controls exhibited substantially greater divergence. Increasing Gene Ontology graph distance broadened PLM-distance distributions, and leaf-parent comparisons demonstrated significant functional ordering (Wilcoxon
conclusionsPLM embeddings provide a scalable framework for comparative proteome characterization, complement conventional sequence-based analyses, and prioritize orthologs or protein regions with elevated functional divergence for experimental validation in cross-species pharmacology, toxicology, and systems biology.
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