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通过基于扩散的对抗学习剖析空间转录组学中的时空结构

Dissecting Spatiotemporal Structures in Spatial Transcriptomics via Diffusion-Based Adversarial Learning.

作者信息

Wang Haiyun, Zhao Jianping, Nie Qing, Zheng Chunhou, Sun Xiaoqiang

机构信息

College of Mathematics and System Sciences, Xinjiang University, Urumqi, China.

Department of Mathematics and Department of Developmental and Cell Biology, NSF-Simons Center for Multiscale Cell Fate Research, University of California Irvine, Irvine, CA, USA.

出版信息

Research (Wash D C). 2024 May 29;7:0390. doi: 10.34133/research.0390. eCollection 2024.

Abstract

Recent advancements in spatial transcriptomics (ST) technologies offer unprecedented opportunities to unveil the spatial heterogeneity of gene expression and cell states within tissues. Despite these capabilities of the ST data, accurately dissecting spatiotemporal structures (e.g., spatial domains, temporal trajectories, and functional interactions) remains challenging. Here, we introduce a computational framework, PearlST (partial differential equation [PDE]-enhanced adversarial graph autoencoder of ST), for accurate inference of spatiotemporal structures from the ST data using PDE-enhanced adversarial graph autoencoder. PearlST employs contrastive learning to extract histological image features, integrates a PDE-based diffusion model to enhance characterization of spatial features at domain boundaries, and learns the latent low-dimensional embeddings via Wasserstein adversarial regularized graph autoencoders. Comparative analyses across multiple ST datasets with varying resolutions demonstrate that PearlST outperforms existing methods in spatial clustering, trajectory inference, and pseudotime analysis. Furthermore, PearlST elucidates functional regulations of the latent features by linking intercellular ligand-receptor interactions to most contributing genes of the low-dimensional embeddings, as illustrated in a human breast cancer dataset. Overall, PearlST proves to be a powerful tool for extracting interpretable latent features and dissecting intricate spatiotemporal structures in ST data across various biological contexts.

摘要

空间转录组学(ST)技术的最新进展为揭示组织内基因表达和细胞状态的空间异质性提供了前所未有的机会。尽管ST数据具有这些能力,但准确剖析时空结构(如空间域、时间轨迹和功能相互作用)仍然具有挑战性。在这里,我们介绍了一个计算框架PearlST(ST的偏微分方程[PDE]增强对抗图自动编码器),用于使用PDE增强对抗图自动编码器从ST数据中准确推断时空结构。PearlST采用对比学习来提取组织学图像特征,集成基于PDE的扩散模型以增强对域边界处空间特征的表征,并通过Wasserstein对抗正则化图自动编码器学习潜在的低维嵌入。对多个不同分辨率的ST数据集进行的比较分析表明,PearlST在空间聚类、轨迹推断和伪时间分析方面优于现有方法。此外,如在一个人类乳腺癌数据集中所示,PearlST通过将细胞间配体-受体相互作用与低维嵌入的最主要贡献基因联系起来,阐明了潜在特征的功能调控。总体而言,PearlST被证明是一种强大的工具,可用于提取可解释的潜在特征,并剖析各种生物学背景下ST数据中复杂的时空结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3760/11134684/0fd60695d4e0/research.0390.fig.001.jpg

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