TCRcloud: a global visualization tool for T-cell and B-cell receptor transcripts

Area of Science:

• Immunology
• Bioinformatics
• Computational Biology

Background:

• Deep T-cell receptor (TCR) sequencing analyzes TCR repertoire in clinical specimens to understand immune responses.
• Clonal T-cell expansion can be antigen-driven or due to bystander activation during anti-cancer immunity.
• Existing analytical tools for TCR composition lack intuitive visualization capabilities.

Purpose of the Study:

• To introduce TCRcloud, an open-access platform for visualizing TCR diversity in cellular immune responses.
• To address the need for intuitive visualization of TCR changes, such as clonal replacement, in response to therapies like immune checkpoint inhibitors (ICIs).
• To analyze real-world data from patients with pancreatic cancer to demonstrate TCR and B-cell receptor (BCR) dynamics.

Main Methods:

• Developed TCRcloud, an open-source computational tool compatible with Adaptive Immune Receptor Repertoire (AIRR) standards for TCR and BCR data.
• Utilized a public dataset linking TCR composition with clinical responses to ICI treatment.
• Applied TCRcloud to visualize TCR and BCR data from blood and tumor tissues of three pancreatic cancer patients.

Main Results:

• TCRcloud screens a TCR data warehouse for patterns like CDR3 length, unique transcripts, convergence, and various diversity indices (D50, Gini, Shannon, Gini-Simpson, Chao1).
• The platform visualizes amino acid usage in TCR and BCR CDR3 regions.
• Demonstrated molecular changes in CDR3 TCR datasets associated with clinical responses in cancer patients and visualized dynamics in pancreatic cancer patient samples.

Conclusions:

• TCRcloud provides intuitive visualization of molecular TCR compositions and repertoire measurements.
• The platform integrates multiple TCR indices into a single radar plot for comprehensive analysis.
• TCRcloud facilitates visualization of V-gene usage and CDR3 amino acid frequencies, enabling intuitive understanding of TCR and BCR composition changes in response to immunotherapy.