INSPIRE: interpretable, flexible and spatially-aware integration of multiple spatial transcriptomics datasets from diverse sources

Recent advances in spatial transcriptomics technologies have led to a growing number of diverse datasets, offering unprecedented opportunities to explore tissue organizations and functions within spatial contexts. However, it remains a significant challenge to effectively integrate and interpret these data, often originating from different samples, technologies, and developmental stages. In this paper, we present INSPIRE, a deep learning method for integrative analyses of multiple spatial transcriptomics datasets to address this challenge. With designs of graph neural networks and an adversarial learning mechanism, INSPIRE enables spatially informed and adaptable integration of data from varying sources. By incorporating non-negative matrix factorization, INSPIRE uncovers interpretable spatial factors with corresponding gene programs, revealing tissue architectures, cell type distributions and biological processes. We demonstrate the capabilities of INSPIRE by applying it to human cortex slices from different samples, mouse brain slices with complementary views, mouse hippocampus and embryo slices generated through different technologies, and spatiotemporal organogenesis atlases containing half a million spatial spots. INSPIRE shows superior performance in identifying detailed biological signals, effectively borrowing information across distinct profiling technologies, and elucidating dynamical changes during embryonic development. Furthermore, we utilize INSPIRE to build 3D models of tissues and whole organisms from multiple slices, demonstrating its power and versatility.