Multi-species integration, alignment and annotation of single-cell RNA-seq data with CAMEX

Single-cell RNA-seq (scRNA-seq) data from multiple species present remarkable opportunities to explore cellular origins and evolution. However, integrating and annotating scRNA-seq data across different species remains challenging due to the variations in sequencing techniques, ambiguity of homologous relationships, and limited biological knowledge. To tackle the above challenges, we introduce CAMEX, a heterogeneous Graph Neural Network (GNN) tool that leverages many-to-many homologous relationships for multi-species integration, alignment, and annotation of scRNA-seq data from multiple species. Notably, CAMEX outperforms state-of-the-art methods integration on various cross-species benchmarking datasets (ranging from one to eleven species). Besides, CAMEX facilitates the alignment of diverse species across different developmental stages, significantly enhancing our understanding of organ and organism origins. Furthermore, CAMEX enables the detection of species-specific cell types and marker genes through cell and gene embedding. In short, CAMEX holds the potential to provide invaluable insights into how evolutionary forces operate across different species at single-cell resolution.

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Publication Details

Journal
Nature Communications
Published
2026-02-21
DOI
https://doi.org/10.1038/s41467-026-69696-3
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
0.00

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article

Multi-species integration, alignment and annotation of single-cell RNA-seq data with CAMEX

De-Shuang Huang, Zhen-Hao Guo, Shihua Zhang
Nature Communications
Single-cell and spatial transcriptomics
article

Multi-species integration, alignment and annotation of single-cell RNA-seq data with CAMEX

De-Shuang Huang, Zhen-Hao Guo, Shihua Zhang
article en

Abstract

Single-cell RNA-seq (scRNA-seq) data from multiple species present remarkable opportunities to explore cellular origins and evolution. However, integrating and annotating scRNA-seq data across different species remains challenging due to the variations in sequencing techniques, ambiguity of homologous relationships, and limited biological knowledge. To tackle the above challenges, we introduce CAMEX, a heterogeneous Graph Neural Network (GNN) tool that leverages many-to-many homologous relationships for multi-species integration, alignment, and annotation of scRNA-seq data from multiple species. Notably, CAMEX outperforms state-of-the-art methods integration on various cross-species benchmarking datasets (ranging from one to eleven species). Besides, CAMEX facilitates the alignment of diverse species across different developmental stages, significantly enhancing our understanding of organ and organism origins. Furthermore, CAMEX enables the detection of species-specific cell types and marker genes through cell and gene embedding. In short, CAMEX holds the potential to provide invaluable insights into how evolutionary forces operate across different species at single-cell resolution.

Nature Communications
Tongji University (CN), Chinese Academy of Sciences (CN), Academy of Mathematics and Systems Science (CN), Shanghai East Hospital (CN), University of Chinese Academy of Sciences (CN), Ningbo Institute of Industrial Technology (CN)
National Natural Science Foundation of China, Guizhou Science and Technology Department, National Key Research and Development Program of China, Natural Science Foundation of Zhejiang Province
Life in Land
Openalex Percentile: Top 46%
Single-cell and spatial transcriptomics
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Multi-species integration, alignment and annotation of single-cell RNA-seq data with CAMEX — De-Shuang Huang, Zhen-Hao Guo, et al. · Nature Communications (2026) | TGRS Research Map | TGRS