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routineHealthcare & BiomedicalDPO2607.16263

Preference-based Antibody Expression Ranking: Scaling with Large-scale Weak Supervision

Josh Qixuan Sun, Morteza Babaie, Wenyang Hou, Mark Crowley, David Young

cs.LG cs.CE q-bio.QM

Abstract

Antibody expression ranking is a critical task in antibody design, yet its modelling is severely hindered by the scarcity of labeled experimental data. To address this, we propose a unified preference-based learning framework that integrates scarce quantitative expression data with large-scale weak positive supervision from immunization data. We adapt Direct Preference Optimization (DPO) to protein language models by introducing a union-masked log-likelihood approximation and IMGT-based alignment, enabling efficient training on variable-length sequences. Evaluating on a diverse internal dataset of 1254 labeled sequences and 4 million unlabeled camelid-derived antibodies, we show that our method consistently outperforms baselines on most metrics. Our results demonstrate that preference learning can effectively learn from weak supervision, providing a scalable solution for antibody expressibility optimization in data-constrained settings. Project page: https://kisoji-biotechnology-inc.github.io/Preference-Expression-Ranking/.

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Classified with taxonomy v2 on Sat, 5 Sept 2026.

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