Cross-modal integration of bulk RNA-seq and single-cell RNA sequencing data to reveal T-cell exhaustion in colorectal cancer.

ABSTRACT

Colorectal cancer (CRC) is a relatively common malignancy clinically and the second leading cause of cancer-related deaths. Recent studies have identified T-cell exhaustion as playing a crucial role in the pathogenesis of CRC. A long-standing challenge in the clinical management of CRC is to understand how T cells function during its progression and metastasis, and whether potential therapeutic targets for CRC treatment can be predicted through T cells. Here, we propose DeepTEX, a multi-omics deep learning approach that integrates cross-model data to investigate the heterogeneity of T-cell exhaustion in CRC. DeepTEX uses a domain adaptation model to align the data distributions from two different modalities and applies a cross-modal knowledge distillation model to predict the heterogeneity of T-cell exhaustion across diverse patients, identifying key functional pathways and genes. DeepTEX offers valuable insights into the application of deep learning in multi-omics, providing crucial data for exploring the stages of T-cell exhaustion associated with CRC and relevant therapeutic targets.