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scTrans:稀疏注意力助力单细胞RNA测序数据中快速且准确的细胞类型注释。

scTrans: Sparse attention powers fast and accurate cell type annotation in single-cell RNA-seq data.

作者信息

Zou Zhiyi, Liu Ying, Bai Yuting, Luo Jiawei, Zhang Zhaolei

机构信息

College of Computer Science and Electronic Engineering, Hunan University, Changsha, Hunan, China.

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.

出版信息

PLoS Comput Biol. 2025 Apr 4;21(4):e1012904. doi: 10.1371/journal.pcbi.1012904. eCollection 2025 Apr.

Abstract

Cell type annotation is crucial in single-cell RNA sequencing data analysis because it enables significant biological discoveries and deepens our understanding of tissue biology. 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's generalization performance and adaptability to novel datasets. To mitigate this issue, we developed scTrans, a single cell Transformer-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.

摘要

细胞类型注释在单细胞RNA测序数据分析中至关重要,因为它能够实现重大的生物学发现,并加深我们对组织生物学的理解。鉴于单细胞RNA测序数据具有高维且高度稀疏的特性,大多数现有的注释工具都聚焦于高变基因以降低维度和计算量。然而,这种方法不可避免地会导致信息丢失,可能会削弱模型的泛化性能以及对新数据集的适应性。为了缓解这个问题,我们开发了scTrans,这是一种基于单细胞Transformer的模型,它采用稀疏注意力来利用所有非零基因,从而在最小化信息丢失的同时有效降低输入数据的维度。我们通过对小鼠细胞图谱中的31种不同组织进行细胞类型注释,验证了scTrans的速度和准确性。值得注意的是,即使对于接近一百万个细胞的数据集,scTrans也能在有限的计算资源下高效地进行细胞类型注释。此外,scTrans展现出强大的泛化能力,能够准确注释新数据集中的细胞并生成高质量的潜在表示,这对于精确聚类和轨迹分析至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a904/11970913/c8cd456147f5/pcbi.1012904.g001.jpg

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