SEAL: Semantic-Aware Contrastive Learning for scRNA-Seq Clustering

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Authors: Yixuan Ye, Jiawen Sun, Liang Peng, Dan Yang, Jiajun Xian, Wenjun Shen, Cheng Liu
Cited by: 1
References: 50

Abstract

The development of single-cell RNA sequencing (scRNA-seq) technology has enabled the exploration of biological processes at the cellular level. A critical task in scRNA-seq data analysis is the unsupervised clustering of cells to distinguish different cell types. While various clustering methods have been successfully developed for scRNA-seq data, they still face limitations, particularly in terms of unstable clustering performance. This is often due to their inability to fully capture the intrinsic properties of cells, especially in the presence of high dropout rates and noise in the data. In this work, we propose a SEmantic-Aware contrastive Learning (SEAL) approach for scRNA-seq clustering. Specifically, we randomly mask the gene expression of each cell to generate two different augmentations of the cell data, and then apply semantic-aware contrastive learning to capture semantically invariant representations across these augmentations by leveraging semantic information from generated pseudo-labels. Experimental results demonstrate that our method effectively learns biologically meaningful representations and accurately identifies cell types.

Fields of Study & Subjects

Single-cell and spatial transcriptomics Domain Adaptation and Few-Shot Learning Genomics and Phylogenetic Studies

Publication details

Journal / source
IEEE Transactions on Computational Biology and Bioinformatics
Publisher
Institute of Electrical and Electronics Engineers (IEEE)
Volume
23
Issue
3
Pages
1136–1147
Publication date
3 March 2026
Language
EN