Integrating single-cell RNA-seq datasets with substantial batch effects.
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| Abstract | Integration of single-cell RNA-sequencing (scRNA-seq) datasets is standard in scRNA-seq analysis. Nevertheless, current computational methods struggle to harmonize datasets across systems such as species, organoids and primary tissue, or different scRNA-seq protocols, including single-cell and single-nuclei. Conditional variational autoencoders (cVAE) are a popular integration method, however, existing strategies for stronger batch correction have limitations. Increasing the Kullback-Leibler divergence regularization does not improve integration and adversarial learning removes biological signals. Here, we propose sysVI, a cVAE-based method employing VampPrior and cycle-consistency constraints. We show that sysVI integrates across systems and improves biological signals for downstream interpretation of cell states and conditions. |
| Year of Publication | 2025
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| Journal | BMC genomics
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| Volume | 26
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| Issue | 1
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| Pages | 974
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| Date Published | 10/2025
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| ISSN | 1471-2164
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| DOI | 10.1186/s12864-025-12126-3
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| PubMed ID | 41168710
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