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Abstract Protein language models (pLMs) have been widely adopted for various protein and peptide-related downstream tasks and demonstrated promising performance. However, short peptides are significantly underrepresented in commonly used pLM training datasets. For example, only 2.8% of sequences in the UniProt Reference Cluster (UniRef) contain fewer than 50 residues, which potentially limits the effectiveness of pLMs for peptide-specific applications. Here, we present PepBERT, a lightweight and efficient peptide language model specifically designed for encoding peptide sequences. Two versions of the model—PepBERT-large (4.9 million parameters) and PepBERT-small (1.86 million parameters)—were pretrained from scratch using four custom peptide datasets and evaluated on nine peptide-related downstream prediction tasks. Both PepBERT models achieved performance superior to or comparable to the benchmark model, ESM-2 with 7.5 million parameters, on 8 out of 9 datasets. Overall, PepBERT provides a compact yet effective solution for generating high-quality peptide representations for downstream applications. By enabling more accurate representation and prediction of bioactive peptides, PepBERT can accelerate the discovery of food-derived bioactive peptides with health-promoting properties, supporting the development of sustainable functional foods and value-added utilization of food processing by-products. The datasets, source codes, pretrained models, and tutorials for the usage of PepBERT are available athttps://github.com/dzjxzyd/PepBERT.more » « lessFree, publicly-accessible full text available April 14, 2026
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Du, Zhenjiao; Fu, Weimin; Guo, Xiaolong; Caragea, Doina; Li, Yonghui (, Journal of Chemical Information and Modeling)Free, publicly-accessible full text available March 24, 2026
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