CellMirror: Deciphering Cell Populations from Spatial Transcriptomics Data by Interpretable Contrastive Learning

Spatial transcriptomics (ST) has enabled us elucidating tumor microenvironments, however, the technological limitations without single-cell resolution severely hinder its application. Here, we propose CellMirror, an interpretable contrastive learning model to decipher heterogeneous cell populations in ST data by single-cell RNA-sequencing (scRNA-seq) data. Specifically, CellMirror learns the disentangled shared (representing biological variations in both data) and salient features (specific to ST data) by two contrastive variational encoders, while constructing the relations between genes and features by a shared linear decoder. In various cancer samples, CellMirror outperforms other tools in learning common features for label transfer, and interpretation of features. Particularly, in breast cancer studies, CellMirror detects finer domains in ST data missed by other methods, and is robust to dissect cell populations in ST data using independent scRNA-seq data. These results demonstrate applications of CellMirror in interpreting the complex tumor structure in ST data by integrating scRNA-seq data.