Unified cross-modality integration and analysis of T cell receptors and T cell transcriptomes by low-resource-aware representation learning

作者：Yicheng Gao, Kejing Dong, Yuli Gao, Xuan Jin, Jingya Yang, Gang Yan, Qi Liu · 发表于：Cell Genomics · 年份：2024 · DOI：10.1016/j.xgen.2024.100553 · 被引用次数：14 · 研究领域：vaccines and immunoinformatics approaches、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) are pivotal for investigating T cell heterogeneity. Integrating these modalities, which is expected to uncover profound insights in immunology that might otherwise go unnoticed with a single modality, faces computational challenges due to the low-resource characteristics of the multimodal data. Herein, we present UniTCR, a novel low-resource-aware multimodal representation learning framework designed for the unified cross-modality integration, enabling comprehensive T cell analysis. By designing a dual-modality contrastive learning module and a single-modality preservation module to effectively embed each modality into a common latent space, UniTCR demonstrates versatility in connecting TCR sequences with T cell transcriptomes across various tasks, including single-modality analysis, modality gap analysis, epitope-TCR binding prediction, and TCR profile cross-modality generation, in a low-resource-aware way. Extensive evaluations conducted on multiple scRNA-seq/TCR-seq paired datasets showed the superior performance of UniTCR, exhibiting the ability of exploring the complexity of immune system.