scMODAL: a general deep learning framework for comprehensive single-cell multi-omics data alignment with feature links

Gefei Wang, Jia Zhao, Yingxin Lin, Tianyu Liu, Yize Zhao and Hongyu Zhao ()
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Gefei Wang: Yale University
Jia Zhao: Yale University
Yingxin Lin: Yale University
Tianyu Liu: Yale University
Yize Zhao: Yale University
Hongyu Zhao: Yale University

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Recent advancements in single-cell technologies have enabled comprehensive characterization of cellular states through transcriptomic, epigenomic, and proteomic profiling at single-cell resolution. These technologies have significantly deepened our understanding of cell functions and disease mechanisms from various omics perspectives. As these technologies evolve rapidly and data resources expand, there is a growing need for computational methods that can integrate information from different modalities to facilitate joint analysis of single-cell multi-omics data. However, integrating single-cell omics datasets presents unique challenges due to varied feature correlations and technology-specific limitations. To address these challenges, we introduce scMODAL, a deep learning framework tailored for single-cell multi-omics data alignment using feature links. scMODAL integrates datasets with limited known positively correlated features, leveraging neural networks and generative adversarial networks to align cell embeddings and preserve feature topology. Our experiments demonstrate scMODAL’s effectiveness in removing unwanted variation, preserving biological information, and accurately identifying cell subpopulations across diverse datasets. scMODAL not only advances integration tasks but also supports downstream analyses such as feature imputation and feature relationship inference, offering a robust solution for advancing single-cell multi-omics research.

Date: 2025
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DOI: 10.1038/s41467-025-60333-z

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