Yu-An Huang, School of Computer Science, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, China. E-mail: zhuhongyou@gmail.com; yuanhuang@nwpu.edu.cn
Abstract
Aims: Single-cell RNA sequencing has emerged as a cornerstone technology in tumor microenvironment research. Accurate cell-type annotation is fundamental to downstream scRNA-seq analysis. However, automated tools are often highly sensitive to dataset noise and show limited adaptability in cross-patient scenarios. To address these challenges, we propose scAdaptAnno, a graph-based target domain adaptation framework for cross-patient single-cell annotation.
Methods: In the graph construction phase, scAdaptAnno integrates both gene expression similarity and biological prior knowledge to build a more biologically meaningful cell graph. By leveraging cell representations enriched with biological priors to mitigate noise in gene expression data and by implementing a bidirectional adaptation mechanism, the model achieves source-free target domain alignment.
Results: We performed comprehensive benchmarking against nine leading methods across multiple datasets spanning various cancer types. The results demonstrate that scAdaptAnno achieves state-of-the-art performance.
Conclusion: scAdaptAnno is a robust and accurate single-cell annotation tool that excels in cross-patient cell-type annotation transfer. By integrating biologically informed graph construction and bidirectional source-free domain adaptation, it delivers reliable, noise-resistant performance across diverse tumor microenvironments, providing an effective solution for automated cell-type annotation in multi-patient scRNA-seq studies.
Keywords
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© The Author(s) 2026. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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