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

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

Cell Genomics, 2024 · DOI: https://doi.org/10.1016/j.xgen.2024.100553 · Published: May 8, 2024

ImmunologyBioinformatics

Simple Explanation

This paper introduces UniTCR, a new computer program designed to combine and analyze two types of data from T cells: their gene activity (transcriptomes) and their T cell receptors (TCRs). This helps researchers better understand the diversity of T cells. UniTCR is designed to work well even when there isn't a lot of data available, which is a common problem when studying T cells. It uses special techniques to learn how the gene activity and TCRs are related, without losing important details from either type of data. The program can perform several tasks, such as analyzing gene activity alone, finding key differences between gene activity and TCRs, predicting how TCRs bind to specific targets (epitopes), and even creating gene activity profiles based on TCR information. Tests on real datasets show that UniTCR works very well.

Study Duration
Not specified
Participants
scRNA-seq/TCR-seq paired datasets
Evidence Level
Not specified

Key Findings

  • 1
    UniTCR enables detailed single-modality analysis by incorporating information from the other modality, offering a detailed understanding beyond what conventional single-modality approaches provide.
  • 2
    By analyzing the modality gap between gene expression and TCR data, UniTCR can identify potentially functional T cell clusters via outlier detection.
  • 3
    UniTCR demonstrates superior performance in epitope-TCR binding prediction across various testing scenarios, highlighting the benefits of incorporating gene expression profile information.

Research Summary

Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) are pivotal for investigating T cell heterogeneity. 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. 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.

Practical Implications

Enhanced T Cell Analysis

UniTCR provides a more holistic view of T cells by integrating gene expression and TCR data, leading to a more detailed understanding of T cell function and heterogeneity.

Discovery of Functional T Cells

The modality gap analysis in UniTCR can identify functionally relevant T cell clusters that might be missed by single-modality analyses, which could lead to the discovery of new therapeutic targets.

Improved Epitope-TCR Binding Prediction

UniTCR's superior performance in predicting epitope-TCR binding can aid in the development of targeted immunotherapies and vaccines.

Study Limitations

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