用稀疏参考增强扩散模型,提升单细胞数据生成的准确性。
Improving scDiffusion with Sparsity-Biased Classifier-Free Guidance

- 用刻意简化的稀疏参考替代原无条件分支,增强引导信号。
- 在5个公开数据集上,标记基因表达和细胞类型一致性均优于标准方法。
- 无需重新训练,适合直接部署于现有生成模型,适用于生物研究者。
单细胞RNA测序(scRNA-seq)已成为现代细胞生物学的关键工具,生成准确的合成scRNA-seq数据日益重要。尽管扩散模型在条件生成方面表现良好,但现有引导策略(包括分类器引导和无分类器引导,CFG)依赖于一个试图逼近真实边缘分布的无条件分支,该分支可能保留显著的基因特异性结构,限制引导效果。受近期工作启发——使用有意退化的参考可有效引导扩散模型,我们提出一种稀疏偏置的无分类器引导(SB-CFG)策略用于scRNA-seq生成。与拟合“中性”边缘分布不同,SB-CFG在无条件分支中引入一个故意信息不足的稀疏参考,移除基因身份,仅保留粗粒度稀疏性统计。这一“劣质”参考增强了条件与无条件预测间的差异,从而在采样过程中产生更强、更有效的引导。我们在五个公开scRNA-seq数据集上评估了SB-CFG作为无训练采样改进的效果。实验结果表明,相比标准CFG采样,其在标记基因表达保真度、细胞类型一致性和稀疏性保持方面均有持续提升,说明SB-CFG能更好地捕捉生物上合理的基因表达模式。
原文摘要 · Abstract (English)
Single-cell RNA sequencing (scRNA-seq) has become an essential tool in modern cellular biology, and generating accurate synthetic scRNA-seq data is becoming increasingly important. Although diffusion models have achieved promising results in conditional scRNA-seq generation, existing guidance strategies, including classifier guidance and classifier-free guidance (CFG), rely on an unconditional branch trained to approximate the true marginal distribution, which may retain substantial gene-specific structure and limit guidance effectiveness. Inspired by recent work showing that diffusion models can be effectively guided using intentionally degraded references, we propose a sparsity-biased classifier-free guidance (SB-CFG) strategy for scRNA-seq generation. Rather than approximating the assumed "neutral" marginal distribution, SB-CFG introduces a deliberately under-informative sparse reference for the unconditional branch, removing gene identity while preserving only coarse sparsity statistics. This "bad" reference amplifies the contrast between conditional and unconditional predictions, leading to stronger and more effective guidance during sampling. We evaluated SB-CFG as a training-free sampling modification on five publicly available scRNA-seq datasets. Experimental results demonstrate consistent improvements over standard CFG-based sampling in terms of marker gene expression fidelity, cell-type consistency, and sparsity preservation, indicating that SB-CFG better captures biologically meaningful gene expression patterns.
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