Deep learning in integrating spatial transcriptomics with other modalities.

Spatial transcriptomics technologies have been extensively applied in biological research, enabling the study of transcriptome while preserving the spatial context of tissues. Paired with spatial transcriptomics data, platforms often provide histology and (or) chromatin images, which capture cellular morphology and chromatin organization. Additionally, single-cell RNA sequencing (scRNA-seq) data from matching tissues often accompany spatial data, offering a transcriptome-wide gene expression profile of individual cells. Integrating such additional data from other modalities can effectively enhance spatial transcriptomics data, and, conversely, spatial transcriptomics data can supplement scRNA-seq with spatial information. Moreover, the rapid development of spatial multi-omics technology has spurred the demand for the integration of spatial multi-omics data to present a more detailed molecular landscape within tissues. Numerous deep learning (DL) methods have been developed for integrating spatial transcriptomics with other modalities. However, a comprehensive review of DL approaches for integrating spatial transcriptomics data with other modalities remains absent. In this study, we systematically review the applications of DL in integrating spatial transcriptomics data with other modalities. We first delineate the DL techniques applied in this integration and the key tasks involved. Next, we detail these methods and categorize them based on integrated modality and key task. Furthermore, we summarize the integration strategies of these integration methods. Finally, we discuss the challenges and future directions in integrating spatial transcriptomics with other modalities, aiming to facilitate the development of robust computational methods that more comprehensively exploit multimodal information.