2025/12/10 by Pu‐Kun Liu, Mengren, Liu +5
Biochemistry, Genetics and Molecular Biology · Medicine · #Biomedical Text Mining and Ontologies #FOS: Computer and information sciences #Machine Learning (cs.LG) #Monoclonal and Polyclonal Antibodies Research #vaccines and immunoinformatics approaches
paper · pdf · doi:10.48550/arxiv.2512.09894
openalex publication_date 2025/12/10 · openalex created_date 2025/12/12 · openalex updated_date 2026/07/28
Recent advances in protein language models (PLMs) have demonstrated remarkable capabilities in understanding protein sequences. However, the extent to which different model architectures capture antibody-specific biological properties remains unexplored. In this work, we systematically investigate how architectural choices in PLMs influence their ability to comprehend antibody sequence characteristics and functions. We evaluate three state-of-the-art PLMs-AntiBERTa, BioBERT, and ESM2--against a general-purpose language model (GPT-2) baseline on antibody target specificity prediction tasks. Our results demonstrate that while all PLMs achieve high classification accuracy, they exhibit distinct biases in capturing biological features such as V gene usage, somatic hypermutation patterns, and isotype information. Through attention attribution analysis, we show that antibody-specific models like AntiBERTa naturally learn to focus on complementarity-determining regions (CDRs), while general protein models benefit significantly from explicit CDR-focused training strategies. These findings provide insights into the relationship between model architecture and biological feature extraction, offering valuable guidance for future PLM development in computational antibody design.