AbLWR:A Context-Aware Listwise Ranking Framework for Antibody-Antigen Binding Affinity Prediction via Positive-Unlabeled Learning

TL;DR

AbLWR introduces a listwise ranking framework with PU learning and self-attention to improve antibody-antigen affinity prediction, effectively handling label sparsity and antigenic variation.

Contribution

It reformulates affinity prediction as a listwise ranking problem and employs novel contrastive and meta-learning techniques for robustness.

Findings

Outperforms state-of-the-art methods with over 10% improvement in P@1.

Effectively captures subtle affinity differences through self-attention.

Demonstrates practical utility in influenza and IL-33 case studies.

Abstract

Accurate prediction of antibody-antigen binding affinity is fundamental to therapeutic design, yet remains constrained by severe label sparsity and the complexity of antigenic variations. In this paper, we propose AbLWR (Antibody-antigen binding affinity List-Wise Ranking), a novel framework that reformulates the conventional affinity regression task as a listwise ranking problem. To mitigate label sparsity, AbLWR incorporates a PU (Positive-Unlabeled) learning mechanism leveraging a dual-level contrastive objective and meta-optimized label refinement to learn robust representations. Furthermore, we address antigenic variation by employing a homologous antigen sampling strategy where Multi-Head Self-Attention (MHSA) explicitly models inter-sample relationships within training lists to capture subtle affinity nuances. Extensive experiments demonstrate that AbLWR significantly outperforms state-of-the-art baselines, improving the Precision@1 (P@1) by over 10$\%$ in randomized cross-validation experiments. Notably, case studies on Influenza and IL-33 validate its practical utility, demonstrating robust ranking consistency in distinguishing subtle viral mutations and efficiently prioritizing top-tier candidates for wet-lab screening.