提出可扩展的scMRDR框架,实现无配对单细胞多组学数据高效整合。
scMRDR: A scalable and flexible framework for unpaired single-cell multi-omics data integration
- 用β-VAE分离共享与特异性表征,结合正则化与对抗训练增强对齐。
- 在基准数据上实现优异批次校正与生物信号保留,支持超大规模数据。
- 适用于两组以上多组学整合,适合大规模生物发现研究。
单细胞测序技术推动了多种分子模态的高分辨率分析,但无配对多组学单细胞数据整合仍具挑战。现有方法依赖配对信息或先验对应关系,或需计算全局成对耦合矩阵,限制了可扩展性与灵活性。本文提出一种可扩展且灵活的生成式框架scMRDR(single-cell Multi-omics Regularized Disentangled Representations),通过设计的β-VAE架构将每个细胞的潜在表征分解为模态共享与模态特异成分,引入等距正则化以保持组内生物异质性,采用对抗目标促进跨模态对齐,并使用掩码重建损失策略处理模态缺失问题。该方法在基准数据集上表现出色,涵盖批次校正、模态对齐与生物信号保留。关键优势在于可有效扩展至大规模数据集,支持超过两个组学的整合,为大规模多组学数据整合与下游生物学发现提供强大灵活的解决方案。
原文摘要 · Abstract (English)
Advances in single-cell sequencing have enabled high-resolution profiling of diverse molecular modalities, while integrating unpaired multi-omics single-cell data remains challenging. Existing approaches either rely on pair information or prior correspondences, or require computing a global pairwise coupling matrix, limiting their scalability and flexibility. In this paper, we introduce a scalable and flexible generative framework called single-cell Multi-omics Regularized Disentangled Representations (scMRDR) for unpaired multi-omics integration. Specifically, we disentangle each cell's latent representations into modality-shared and modality-specific components using a well-designed $β$-VAE architecture, which are augmented with isometric regularization to preserve intra-omics biological heterogeneity, adversarial objective to encourage cross-modal alignment, and masked reconstruction loss strategy to address the issue of missing features across modalities. Our method achieves excellent performance on benchmark datasets in terms of batch correction, modality alignment, and biological signal preservation. Crucially, it scales effectively to large-scale datasets and supports integration of more than two omics, offering a powerful and flexible solution for large-scale multi-omics data integration and downstream biological discovery.
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