Tissue characterization at an enhanced resolution across spatial omics platforms with deep generative model

Abstract

Abstract Recent advances in spatial omics have expanded the spectrum of profiled molecular categories beyond transcriptomics. However, many of these technologies are constrained by limited spatial resolution, hindering our ability to deeply characterize intricate tissue architectures. Existing computational methods primarily focus on the resolution enhancement of transcriptomics data, lacking the adaptability to address the emerging spatial omics technologies that profile various omics types. Here, we introduce soScope, a unified generative framework designed to enhance data quality and spatial resolution for molecular profiles obtained from diverse spatial technologies. soScope aggregates multimodal tissue information from omics, spatial relations and images, and jointly infers omics profiles at enhanced resolutions with omics-specific modeling through distribution priors. With comprehensive evaluations on diverse spatial omics platforms, including Visium, Xenium, spatial-CUT&Tag, and slide-DNA/RNA-seq, soScope improves performances in identifying biologically meaningful intestine and kidney architectures, revealing embryonic heart structure that cannot be resolved at the original resolution and correcting sample and technical biases arising from sequencing and sample processing. Furthermore, soScope extends to spatial multiomics technology spatial-CITE-seq and spatial ATAC-RNA-seq, leveraging cross-omics reference for simultaneous multiomics enhancement. soScope provides a versatile tool to improve the utilization of continually expanding spatial omics technologies and resources.