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 ...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.展开更多
基金supported by grants from the National Key R&D Program of China(2021YFF1200903)the National Natural Science Foundation of China(62273364,11931019,11871070,and 62362062)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2020B1515020047)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(231lgbj025)the open fund of Information Materials and Intelligent Sensing Laboratory of Anhui Province(grant no.IMIS202105).
文摘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.
