Momentum Contrast-Enhanced Multimodal Representation Learning for Drug Synergy Prediction.

Gu, Yu; Huang, Xindi; Shi, Lifen; Chen, Leying; Duan, Guihua; Yan, Cheng · Bioinformatics · 2026

basic_science · Level V

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Abstract

Accurate prediction of synergistic drug combinations can accelerate anticancer combination discovery. Existing methods inadequately model higher-order drug-drug-cell-line interactions and drug-disease associations and remain sensitive to sparse and noisy multi-omics data, limiting generalization to unseen cell lines and drug combinations. We present MoCo-MultiSynergy, a multimodal framework that combines modality-specific momentum contrastive learning with heterogeneous hypergraph modeling. The hypergraph represents synergistic drug-drug-cell-line triplets and drug-disease associations, while gated residual propagation refines node representations. Momentum Contrast modules regularize encoded drug and cell-line representations using latent feature masking and Gaussian perturbation. On the O'Neil and NCI-ALMANAC datasets, MoCo-MultiSynergy achieves the highest AUROC and AUPRC across the evaluated settings, with the largest gains when generalizing to unseen cell lines and drug combinations. Source code is available at https://github.com/27167199/MoCo-MultiSynergy.