Contrastive Learning Enables Epitope Overlap Predictions for Targeted Antibody Discovery.

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Tác giả: Parastoo Amlashi, Ivelin S Georgiev, Clinton M Holt, Parker J Jamieson, Alexis K Janke, Toma M Marinov

Ngôn ngữ: eng

Ký hiệu phân loại: 598.412 *Aix

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 683467

 Computational epitope prediction remains an unmet need for therapeutic antibody development. We present three complementary approaches for predicting epitope relationships from antibody amino acid sequences. First, we analyze ~18 million antibody pairs targeting ~250 protein families and establish that a threshold of >
 70% CDRH3 sequence identity among antibodies sharing both heavy and light chain V-genes reliably predicts overlapping-epitope antibody pairs. Next, we develop a supervised contrastive fine-tuning framework for antibody large language models which results in embeddings that better correlate with epitope information than those from pretrained models. Applying this contrastive learning approach to SARS-CoV-2 receptor binding domain antibodies, we achieve 82.7% balanced accuracy in distinguishing same-epitope versus different-epitope antibody pairs and demonstrate the ability to predict relative levels of structural overlap from learning on functional epitope bins (Spearman
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