scAGC: Learning Adaptive Cell Graphs with Contrastive Guidance for Single-Cell Clustering

Fuente: arXiv
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Main Authors: Li, Huifa, Fu, Jie, Zhuang, Xinlin, Yang, Haolin, Ling, Xinpeng, Cheng, Tong, xue, Haochen, Razzak, Imran, Chen, Zhili
Format: Preprint
Published: 2025
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author Li, Huifa
Fu, Jie
Zhuang, Xinlin
Yang, Haolin
Ling, Xinpeng
Cheng, Tong
xue, Haochen
Razzak, Imran
Chen, Zhili
author_facet Li, Huifa
Fu, Jie
Zhuang, Xinlin
Yang, Haolin
Ling, Xinpeng
Cheng, Tong
xue, Haochen
Razzak, Imran
Chen, Zhili
contents Accurate cell type annotation is a crucial step in analyzing single-cell RNA sequencing (scRNA-seq) data, which provides valuable insights into cellular heterogeneity. However, due to the high dimensionality and prevalence of zero elements in scRNA-seq data, traditional clustering methods face significant statistical and computational challenges. While some advanced methods use graph neural networks to model cell-cell relationships, they often depend on static graph structures that are sensitive to noise and fail to capture the long-tailed distribution inherent in single-cell populations.To address these limitations, we propose scAGC, a single-cell clustering method that learns adaptive cell graphs with contrastive guidance. Our approach optimizes feature representations and cell graphs simultaneously in an end-to-end manner. Specifically, we introduce a topology-adaptive graph autoencoder that leverages a differentiable Gumbel-Softmax sampling strategy to dynamically refine the graph structure during training. This adaptive mechanism mitigates the problem of a long-tailed degree distribution by promoting a more balanced neighborhood structure. To model the discrete, over-dispersed, and zero-inflated nature of scRNA-seq data, we integrate a Zero-Inflated Negative Binomial (ZINB) loss for robust feature reconstruction. Furthermore, a contrastive learning objective is incorporated to regularize the graph learning process and prevent abrupt changes in the graph topology, ensuring stability and enhancing convergence. Comprehensive experiments on 9 real scRNA-seq datasets demonstrate that scAGC consistently outperforms other state-of-the-art methods, yielding the best NMI and ARI scores on 9 and 7 datasets, respectively.Our code is available at Anonymous Github.
format Preprint
id arxiv_https___arxiv_org_abs_2508_09180
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle scAGC: Learning Adaptive Cell Graphs with Contrastive Guidance for Single-Cell Clustering
Li, Huifa
Fu, Jie
Zhuang, Xinlin
Yang, Haolin
Ling, Xinpeng
Cheng, Tong
xue, Haochen
Razzak, Imran
Chen, Zhili
Machine Learning
Artificial Intelligence
Accurate cell type annotation is a crucial step in analyzing single-cell RNA sequencing (scRNA-seq) data, which provides valuable insights into cellular heterogeneity. However, due to the high dimensionality and prevalence of zero elements in scRNA-seq data, traditional clustering methods face significant statistical and computational challenges. While some advanced methods use graph neural networks to model cell-cell relationships, they often depend on static graph structures that are sensitive to noise and fail to capture the long-tailed distribution inherent in single-cell populations.To address these limitations, we propose scAGC, a single-cell clustering method that learns adaptive cell graphs with contrastive guidance. Our approach optimizes feature representations and cell graphs simultaneously in an end-to-end manner. Specifically, we introduce a topology-adaptive graph autoencoder that leverages a differentiable Gumbel-Softmax sampling strategy to dynamically refine the graph structure during training. This adaptive mechanism mitigates the problem of a long-tailed degree distribution by promoting a more balanced neighborhood structure. To model the discrete, over-dispersed, and zero-inflated nature of scRNA-seq data, we integrate a Zero-Inflated Negative Binomial (ZINB) loss for robust feature reconstruction. Furthermore, a contrastive learning objective is incorporated to regularize the graph learning process and prevent abrupt changes in the graph topology, ensuring stability and enhancing convergence. Comprehensive experiments on 9 real scRNA-seq datasets demonstrate that scAGC consistently outperforms other state-of-the-art methods, yielding the best NMI and ARI scores on 9 and 7 datasets, respectively.Our code is available at Anonymous Github.
title scAGC: Learning Adaptive Cell Graphs with Contrastive Guidance for Single-Cell Clustering
topic Machine Learning
Artificial Intelligence
url https://arxiv.org/abs/2508.09180