MIST: An interpretable and flexible deep learning framework for single–T cell transcriptome and receptor analysis

Joint analysis of transcriptomic and T cell receptor (TCR) features at single-cell resolution provides a powerful approach for in-depth T cell immune function research. Here, we introduce a deep learning framework for single-T cell transcriptome and receptor analysis, MIST (Multi-insight for T cell). MIST features three latent spaces: gene expression, TCR, and a joint latent space. Through analyses of antigen-specific T cells, and T cell datasets related to lung cancer immunotherapy and COVID19, we demonstrate MIST's interpretability and flexibility. MIST easily and accurately resolves cell function and antigen specificity by vectorizing and integrating transcriptome and TCR data of T cells. In addition, using MIST, we identified the heterogeneity of CXCL13⁺ subsets in lung cancer infiltrating CD8⁺ T cells and their association with immunotherapy, providing additional insights into the functional transition of CXCL13⁺ T cells related to anti-PD-1 therapy that were not reported in the original study.