STRIDE: accurately decomposing and integrating spatial transcriptomics using single-cell RNA sequencing

TLDR

Recent advances in spatial transcriptomics enable unprecedented insight into cellular heterogeneity, yet current technologies limit single‑cell resolution of cellular localization and interactions. The authors aim to develop STRIDE, a computational method that deconvolves cell types from spatial mixtures using topic profiles trained on single‑cell transcriptomics. STRIDE applies topic modeling to spatial transcriptomics data, leveraging single‑cell–derived topic profiles to estimate cell‑type proportions. STRIDE accurately estimates cell‑type proportions with balanced specificity and sensitivity, maps rare cell types and spatially localized genes, identifies cell‑type–specific functional topics, and enables integration of successive sections for three‑dimensional tissue reconstruction, outperforming existing methods and is publicly available at https://github.com/wanglabtongji/STRIDE.

Abstract

The recent advances in spatial transcriptomics have brought unprecedented opportunities to understand the cellular heterogeneity in the spatial context. However, the current limitations of spatial technologies hamper the exploration of cellular localizations and interactions at single-cell level. Here, we present spatial transcriptomics deconvolution by topic modeling (STRIDE), a computational method to decompose cell types from spatial mixtures by leveraging topic profiles trained from single-cell transcriptomics. STRIDE accurately estimated the cell-type proportions and showed balanced specificity and sensitivity compared to existing methods. We demonstrated STRIDE's utility by applying it to different spatial platforms and biological systems. Deconvolution by STRIDE not only mapped rare cell types to spatial locations but also improved the identification of spatially localized genes and domains. Moreover, topics discovered by STRIDE were associated with cell-type-specific functions and could be further used to integrate successive sections and reconstruct the three-dimensional architecture of tissues. Taken together, STRIDE is a versatile and extensible tool for integrated analysis of spatial and single-cell transcriptomics and is publicly available at https://github.com/wanglabtongji/STRIDE.