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Given the high-dimensional and highly sparse nature of single-cell RNA sequencing data, most existing annotation tools focus on highly variable genes to reduce dimensionality and computational load. However, this approach inevitably results in information loss, potentially weakening the model\u2019s generalization performance and adaptability to novel datasets. To mitigate this issue, we developed scTrans, a <jats:bold>s<\/jats:bold>ingle <jats:bold>c<\/jats:bold>ell <jats:bold>Trans<\/jats:bold>former-based model, which employs sparse attention to utilize all non-zero genes, thereby effectively reducing the input data dimensionality while minimizing information loss. We validated the speed and accuracy of scTrans by performing cell type annotation on 31 different tissues within the Mouse Cell Atlas. Remarkably, even with datasets nearing a million cells, scTrans efficiently perform cell type annotation in limited computational resources. Furthermore, scTrans demonstrates strong generalization capabilities, accurately annotating cells in novel datasets and generating high-quality latent representations, which are essential for precise clustering and trajectory analysis.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012904","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T20:01:57Z","timestamp":1743796917000},"page":"e1012904","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["scTrans: Sparse attention powers fast and accurate cell type annotation in single-cell RNA-seq 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