STARK通过自适应图正则化,显著提升超低测序深度下的空间转录组图像去噪效果。
STARK denoises spatial transcriptomics images via adaptive regularization
- 结合核岭回归与动态更新的图拉普拉斯正则化,逐步优化图像质量。
- 在真实数据上标签转移准确率优于现有方法,且理论证明收敛到真值速率为1/√R。
- 适合处理低测序深度数据,对细胞类型识别和基因表达插值有明显优势。
我们提出一种空间转录组图像去噪方法——基于自适应正则化与核函数的时空转录组分析(STARK),特别适用于超低测序深度下揭示细胞身份,并支持基因表达插值。该方法将核岭回归与增量式自适应图拉普拉斯正则化相结合:每轮迭代中,先用固定图进行核岭回归更新图像,再根据新图像更新图结构。通过改进的表示定理,将无限维图像空间问题转化为有限维求解。从纯空间图开始,随图像优化逐步增强图的抗噪能力。该方法通过交替最小化求解块凸目标函数,子问题具闭式解,易于计算;并可证明迭代序列收敛至非凸目标的驻点。统计上,此类驻点以速率$\mathcal{O}(R^{-1/2})$收敛于真实值,其中$R$为读段数。在真实空间转录组数据上的数值实验表明,以标签转移准确率为指标,STARK的去噪性能持续优于对比方法。
原文摘要 · Abstract (English)
We present an approach to denoising spatial transcriptomics images that is particularly effective for uncovering cell identities in the regime of ultra-low sequencing depths, and also allows for interpolation of gene expression. The method -- Spatial Transcriptomics via Adaptive Regularization and Kernels (STARK) -- augments kernel ridge regression with an incrementally adaptive graph Laplacian regularizer. In each iteration, we (1) perform kernel ridge regression with a fixed graph to update the image, and (2) update the graph based on the new image. The kernel ridge regression step involves reducing the infinite dimensional problem on a space of images to finite dimensions via a modified representer theorem. Starting with a purely spatial graph, and updating it as we improve our image makes the graph more robust to noise in low sequencing depth regimes. We show that the aforementioned approach optimizes a block-convex objective through an alternating minimization scheme wherein the sub-problems have closed form expressions that are easily computed. This perspective allows us to prove convergence of the iterates to a stationary point of this non-convex objective. Statistically, such stationary points converge to the ground truth with rate $\mathcal{O}(R^{-1/2})$ where $R$ is the number of reads. In numerical experiments on real spatial transcriptomics data, the denoising performance of STARK, evaluated in terms of label transfer accuracy, shows consistent improvement over the competing methods tested.
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