DuaDeep-SeqAffinity: Dual-Branch Deep Learning for Tri-Stream Sequence-Based Antibody--Antigen Affinity Prediction

Abstract:DuaDeep-SeqAffinity is a sequence-only deep learning framework that predicts antibody--antigen binding affinity directly from primary amino acid sequences, avoiding the cost and scarcity of resolved three-dimensional structures. The antigen and the antibody heavy and light chains are processed as three independent streams, each embedded with a frozen ESM-2 protein language model and passed through parallel Transformer and convolutional neural network (CNN) branches before late fusion, a decoupled design intended to preserve local complementarity-determining region (CDR) signal that monolithic encoders can dilute. On a sequence-disjoint split of the AbRank benchmark, the model achieves a Pearson correlation of 0.683, an R^2 of 0.460, and a pairwise ranking AUC of 0.895, significantly outperforming single-branch ablations (paired t-test, p < 0.05). Attention-map and gradient-based saliency analyses further show that the model preferentially attends to CDR loops and candidate epitope residues, supporting its use as a scalable, structure-free tool for high-throughput antibody screening.

Machine Learning (cs.LG)

arXiv:2512.22007 [cs.LG]

(or arXiv:2512.22007v2 [cs.LG] for this version)

https://doi.org/10.48550/arXiv.2512.22007 Focus to learn more arXiv-issued DOI via DataCite

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