AbRank: A Benchmark Dataset and Metric-Learning Framework for Antibody-Antigen Affinity Ranking

Fuente: arXiv
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Main Authors: Liu, Chunan, Pelissier, Aurelien, Shao, Yanjun, Denzler, Lilian, Martin, Andrew C. R., Paige, Brooks, Martínez, María Rodríguez
Format: Preprint
Published: 2025
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author Liu, Chunan
Pelissier, Aurelien
Shao, Yanjun
Denzler, Lilian
Martin, Andrew C. R.
Paige, Brooks
Martínez, María Rodríguez
author_facet Liu, Chunan
Pelissier, Aurelien
Shao, Yanjun
Denzler, Lilian
Martin, Andrew C. R.
Paige, Brooks
Martínez, María Rodríguez
contents Accurate prediction of antibody-antigen (Ab-Ag) binding affinity is essential for therapeutic design and vaccine development, yet the performance of current models is limited by noisy experimental labels, heterogeneous assay conditions, and poor generalization across the vast antibody and antigen sequence space. We introduce AbRank, a large-scale benchmark and evaluation framework that reframes affinity prediction as a pairwise ranking problem. AbRank aggregates over 380,000 binding assays from nine heterogeneous sources, spanning diverse antibodies, antigens, and experimental conditions, and introduces standardized data splits that systematically increase distribution shift, from local perturbations such as point mutations to broad generalization across novel antigens and antibodies. To ensure robust supervision, AbRank defines an m-confident ranking framework by filtering out comparisons with marginal affinity differences, focusing training on pairs with at least an m-fold difference in measured binding strength. As a baseline for the benchmark, we introduce WALLE-Affinity, a graph-based approach that integrates protein language model embeddings with structural information to predict pairwise binding preferences. Our benchmarks reveal significant limitations in current methods under realistic generalization settings and demonstrate that ranking-based training improves robustness and transferability. In summary, AbRank offers a robust foundation for machine learning models to generalize across the antibody-antigen space, with direct relevance for scalable, structure-aware antibody therapeutic design.
format Preprint
id arxiv_https___arxiv_org_abs_2506_17857
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle AbRank: A Benchmark Dataset and Metric-Learning Framework for Antibody-Antigen Affinity Ranking
Liu, Chunan
Pelissier, Aurelien
Shao, Yanjun
Denzler, Lilian
Martin, Andrew C. R.
Paige, Brooks
Martínez, María Rodríguez
Biomolecules
Machine Learning
Accurate prediction of antibody-antigen (Ab-Ag) binding affinity is essential for therapeutic design and vaccine development, yet the performance of current models is limited by noisy experimental labels, heterogeneous assay conditions, and poor generalization across the vast antibody and antigen sequence space. We introduce AbRank, a large-scale benchmark and evaluation framework that reframes affinity prediction as a pairwise ranking problem. AbRank aggregates over 380,000 binding assays from nine heterogeneous sources, spanning diverse antibodies, antigens, and experimental conditions, and introduces standardized data splits that systematically increase distribution shift, from local perturbations such as point mutations to broad generalization across novel antigens and antibodies. To ensure robust supervision, AbRank defines an m-confident ranking framework by filtering out comparisons with marginal affinity differences, focusing training on pairs with at least an m-fold difference in measured binding strength. As a baseline for the benchmark, we introduce WALLE-Affinity, a graph-based approach that integrates protein language model embeddings with structural information to predict pairwise binding preferences. Our benchmarks reveal significant limitations in current methods under realistic generalization settings and demonstrate that ranking-based training improves robustness and transferability. In summary, AbRank offers a robust foundation for machine learning models to generalize across the antibody-antigen space, with direct relevance for scalable, structure-aware antibody therapeutic design.
title AbRank: A Benchmark Dataset and Metric-Learning Framework for Antibody-Antigen Affinity Ranking
topic Biomolecules
Machine Learning
url https://arxiv.org/abs/2506.17857