用图正则化提升零样本细胞类型注释准确率,无需训练即可增强模型性能。
GRIT: Graph-Regularized Logit Refinement for Zero-shot Cell Type Annotation
- 在PCA构建的k近邻图上约束CLIP logits的局部一致性
- 14个数据集上最高提升10%准确率,超20万细胞规模验证
- 无需训练、兼容任意模型,适合快速部署到新数据
细胞类型注释是单细胞RNA测序(scRNA-seq)数据分析的基础步骤。实践中,人类专家常依赖主成分分析(PCA)揭示的结构,结合k-最近邻(k-NN)图来指导注释,但该过程耗时且难以扩展至大规模数据。近期基于CLIP的模型为自动化注释提供了新路径,例如LangCell可实现零样本注释。尽管表现尚可,其预测仍不理想。本文提出一种原则性的推理阶段范式GRIT,将预训练基础模型的可扩展性与人类专家注释中依赖的结构鲁棒性相融合。具体而言,我们在任务特定的基于PCA的k-NN图上施加零样本CLIP logits的局部一致性。我们在来自4项不同研究的14个已标注的人类scRNA-seq数据集上评估方法,涵盖11个器官和超过20万单细胞。结果表明,本方法持续提升零样本注释准确率,最高提升达10%。进一步分析显示,GRIT能有效通过图结构传播正确信号,将误标细胞拉向更准确的预测。该方法无需训练、模型无关,可作为简单而有效的插件提升零样本细胞类型注释性能。
原文摘要 · Abstract (English)
Cell type annotation is a fundamental step in the analysis of single-cell RNA sequencing (scRNA-seq) data. In practice, human experts often rely on the structure revealed by principal component analysis (PCA) followed by $k$-nearest neighbor ($k$-NN) graph construction to guide annotation. While effective, this process is labor-intensive and does not scale to large datasets. Recent advances in CLIP-style models offer a promising path toward automating cell type annotation. By aligning scRNA-seq profiles with natural language descriptions, models like LangCell enable zero-shot annotation. While LangCell demonstrates decent zero-shot performance, its predictions remain suboptimal. In this paper, we propose a principled inference-time paradigm for zero-shot cell type annotation (GRIT) which bridges the scalability of pre-trained foundation models with the structural robustness relied upon in human expert annotation workflows. Specifically, we enforce local consistency of the zero-shot CLIP logits over the task-specific PCA-based $k$-NN graph. We evaluate our approach on 14 annotated human scRNA-seq datasets from 4 distinct studies, spanning 11 organs and over 200,000 single cells. Our method consistently improves zero-shot annotation accuracy, achieving accuracy gains of up to 10\%. Further analysis showcase the mechanism by which GRIT effectively propagates correct signals through the graph, pulling back mislabeled cells toward more accurate predictions. The method is training-free, model-agnostic, and serves as a simple yet effective plug-in for enhancing zero-shot cell type annotation.
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