# Clustering single-cell multi-omics data via multi-subspace contrastive learning with structural smoothness

**Authors:** Yun Ding, Yangzhen Jiang, Jing Wang, Dayu Tan, Yansen Su, Chunhou Zheng

PMC · DOI: 10.1093/bib/bbag005 · 2026-01-27

## TL;DR

This paper introduces a new method for clustering single-cell multi-omics data using contrastive learning and structural smoothness to improve accuracy and robustness.

## Contribution

The novel scMUSCLE method introduces multi-subspace contrastive learning and adaptive graph convolution for improved single-cell multi-omics clustering.

## Key findings

- scMUSCLE improves clustering accuracy by leveraging structural diversity and contrastive learning.
- The method demonstrates robustness and effectiveness on four benchmark datasets.
- An adaptive feedback mechanism enhances intra-cluster smoothness and clustering performance.

## Abstract

The integration of single-cell multi-omics data can uncover the underlying regulatory basis of diverse cell types and states. However, single-cell data inherently suffer from high levels of noise, sparsity, and intercellular heterogeneity, which pose significant challenges to the accuracy and robustness of clustering algorithms. Most existing multi-omics clustering approaches primarily focus on the integration of omics individuality and commonality across modalities, but they ignore the diverse feature extraction of the low-dimensional representation before the fusion of single-cell multi-omics data, and the feature smoothing consistency of the diverse features after the fusion of single-cell multi-omics data. In order to address above issues, we propose a novel multi-subspace contrastive learning with structural smoothness method for single-cell multi-omics data clustering (scMUSCLE), which is designed to address the challenges inherent in multi-omics data integration. First, the proposed scMUSCLE method leverages the degree structure to enhance structural diversity of each omics modality. Second, we perform multi-subspace contrastive learning to improve the diversity exploration across multi-omics features. Next, we propose an adaptive graph convolution clustering module, which establishes an adaptive feedback mechanism between intra-cluster smoothness and the downstream clustering task. Extensive experiments on four benchmark multi-omics datasets demonstrate the effectiveness and robustness. The source code can be found on the GitHub repository: https://github.com/GodIsGad/scMUSCLE.

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12834668/full.md

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Source: https://tomesphere.com/paper/PMC12834668