A Practice on Antibody Hydrophobic Interaction Chromatography Retention Time Prediction using Pre-Trained Large Language Model Fine-Tuning

Hydrophobicity is a critical property associated with the risk of non-specific binding, and it is commonly assessed using hydrophobic interaction chromatography retention time. Several computational approaches have been developed to predict antibody developability based on pre-trained language models. Such models can be fine-tuned with limited labeled antibody sequences and, in principle, do not require structural information, which is often challenging to obtain. Nevertheless, few studies have achieved strong performance in hydrophobicity prediction without incorporating structural features. Here, we present a case study of fine-tuning the pre-trained model IgBert to predict antibody hydrophobicity. Using Herceptin as a reference, we performed hydrophobic interaction chromatography retention time experiments and generated Herceptin-adjusted datasets. The fine-tuned model achieved a best R2 of 0.916, underscoring the critical role of rigorous data quality control. We also synthesized and validated 20 commercially available antibody sequences, and the results showed that the predicted hydrophobic properties were correctly reflected. Our findings provide practical guidance and highlight considerations for future applications of fine-tuned pre-trained language models in antibody hydrophobicity prediction. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/742939v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@9c814eorg.highwire.dtl.DTLVardef@ed609dorg.highwire.dtl.DTLVardef@62172forg.highwire.dtl.DTLVardef@1e01d37_HPS_FORMAT_FIGEXP M_FIG C_FIG