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IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
TOGAR: Token-gated generative refinement for high-fidelity spatial transcriptomics and robust spatial domain clustering 用于高保真空间转录组学和鲁棒空间域聚类的令牌门控生成改进。
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.ygeno.2025.111179
Dachen Liu , Hua Shi , Yihang Lin , Zhen Chen , Quan Zou
Spatial transcriptomics maps gene expression across tissues, yet data sparsity and noise challenge long-range dependency modeling, limiting accurate spatial domain delineation. In this study, we present TOGAR, a token-gated generative refinement model that unifies denoising, spatial enhancement, and clustering for spatial transcriptomics. Firstly, the model combines a graph convolutional network loss with a loss based on the zero-inflated negative binomial distribution to reduce noise and enhance signal clarity in sparse count data. It then employs a UGate-based diffusion backbone, which integrates token gating, gated linear attention, and rotary positional embedding for generative spatial refinement. Finally, similarity-guided averaging along diffusion trajectories provides stable spot-level estimates, and clustering of the refined representations produces spatial domains with sharp boundaries suitable for downstream analyses. We evaluate TOGAR across three spatial transcriptomics platforms. In benchmarks on twelve slices against seven popular methods, TOGAR consistently achieves or exceeds clustering accuracy, demonstrating superior stability. TOGAR effectively recovers coherent cortical layer organization, delineates fine-grained tumor subdomains associated with immune activity and extracellular matrix remodeling, and generates clearer, biologically interpretable domain boundaries. Notably, TOGAR excels in detecting extremely small and rare spatial structures, successfully identifying biologically important regions that other methods completely miss, while maintaining boundary integrity in complex multi-cluster structures and avoiding issues of over-connectivity or incomplete detection.
空间转录组学绘制跨组织的基因表达,但数据稀疏性和噪声挑战了远程依赖建模,限制了准确的空间域描绘。在这项研究中,我们提出了TOGAR,一个统一了去噪、空间增强和空间转录组聚类的标记门控生成细化模型。首先,该模型将图卷积网络损失与基于零膨胀负二项分布的损失相结合,以降低稀疏计数数据中的噪声,提高信号清晰度。然后,它采用基于gate的扩散主干,该主干集成了令牌门控、门控线性注意和旋转位置嵌入,用于生成空间细化。最后,沿着扩散轨迹的相似性引导平均提供了稳定的点水平估计,并且精细表示的聚类产生具有适合下游分析的明确边界的空间域。我们通过三个空间转录组学平台评估TOGAR。在针对7种常用方法的12个切片的基准测试中,TOGAR始终达到或超过聚类精度,显示出优越的稳定性。TOGAR有效地恢复了连贯的皮质层组织,描绘了与免疫活性和细胞外基质重塑相关的细粒度肿瘤亚域,并产生了更清晰、生物学上可解释的区域边界。值得注意的是,TOGAR在检测极小和罕见的空间结构方面表现出色,成功识别了其他方法完全遗漏的重要生物区域,同时保持了复杂多簇结构的边界完整性,避免了过度连接或检测不完整的问题。
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
IF 3 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-01
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引用次数: 0
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Genomics
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