Soft Graph Clustering for single-cell RNA Sequencing Data

Fuente: arXiv
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Main Authors: Xu, Ping, Wang, Pengfei, Ning, Zhiyuan, Xiao, Meng, Wu, Min, Zhou, Yuanchun
Format: Preprint
Published: 2025
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author Xu, Ping
Wang, Pengfei
Ning, Zhiyuan
Xiao, Meng
Wu, Min
Zhou, Yuanchun
author_facet Xu, Ping
Wang, Pengfei
Ning, Zhiyuan
Xiao, Meng
Wu, Min
Zhou, Yuanchun
contents Clustering analysis is fundamental in single-cell RNA sequencing (scRNA-seq) data analysis for elucidating cellular heterogeneity and diversity. Recent graph-based scRNA-seq clustering methods, particularly graph neural networks (GNNs), have significantly improved in tackling the challenges of high-dimension, high-sparsity, and frequent dropout events that lead to ambiguous cell population boundaries. However, their reliance on hard graph constructions derived from thresholded similarity matrices presents challenges:(i) The simplification of intercellular relationships into binary edges (0 or 1) by applying thresholds, which restricts the capture of continuous similarity features among cells and leads to significant information loss.(ii) The presence of significant inter-cluster connections within hard graphs, which can confuse GNN methods that rely heavily on graph structures, potentially causing erroneous message propagation and biased clustering outcomes. To tackle these challenges, we introduce scSGC, a Soft Graph Clustering for single-cell RNA sequencing data, which aims to more accurately characterize continuous similarities among cells through non-binary edge weights, thereby mitigating the limitations of rigid data structures. The scSGC framework comprises three core components: (i) a zero-inflated negative binomial (ZINB)-based feature autoencoder; (ii) a dual-channel cut-informed soft graph embedding module; and (iii) an optimal transport-based clustering optimization module. Extensive experiments across ten datasets demonstrate that scSGC outperforms 13 state-of-the-art clustering models in clustering accuracy, cell type annotation, and computational efficiency. These results highlight its substantial potential to advance scRNA-seq data analysis and deepen our understanding of cellular heterogeneity.
format Preprint
id arxiv_https___arxiv_org_abs_2507_09890
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Soft Graph Clustering for single-cell RNA Sequencing Data
Xu, Ping
Wang, Pengfei
Ning, Zhiyuan
Xiao, Meng
Wu, Min
Zhou, Yuanchun
Machine Learning
Artificial Intelligence
Genomics
Clustering analysis is fundamental in single-cell RNA sequencing (scRNA-seq) data analysis for elucidating cellular heterogeneity and diversity. Recent graph-based scRNA-seq clustering methods, particularly graph neural networks (GNNs), have significantly improved in tackling the challenges of high-dimension, high-sparsity, and frequent dropout events that lead to ambiguous cell population boundaries. However, their reliance on hard graph constructions derived from thresholded similarity matrices presents challenges:(i) The simplification of intercellular relationships into binary edges (0 or 1) by applying thresholds, which restricts the capture of continuous similarity features among cells and leads to significant information loss.(ii) The presence of significant inter-cluster connections within hard graphs, which can confuse GNN methods that rely heavily on graph structures, potentially causing erroneous message propagation and biased clustering outcomes. To tackle these challenges, we introduce scSGC, a Soft Graph Clustering for single-cell RNA sequencing data, which aims to more accurately characterize continuous similarities among cells through non-binary edge weights, thereby mitigating the limitations of rigid data structures. The scSGC framework comprises three core components: (i) a zero-inflated negative binomial (ZINB)-based feature autoencoder; (ii) a dual-channel cut-informed soft graph embedding module; and (iii) an optimal transport-based clustering optimization module. Extensive experiments across ten datasets demonstrate that scSGC outperforms 13 state-of-the-art clustering models in clustering accuracy, cell type annotation, and computational efficiency. These results highlight its substantial potential to advance scRNA-seq data analysis and deepen our understanding of cellular heterogeneity.
title Soft Graph Clustering for single-cell RNA Sequencing Data
topic Machine Learning
Artificial Intelligence
Genomics
url https://arxiv.org/abs/2507.09890