Abstract
The T cell receptors (TCR) carry critical information regarding T cell functionality. Yet is often overlooked in single cell experiments, which commonly focus on gene expression (GEx)-first analysis. Here we propose a dedicated TCR-first analysis for single T cell data, implemented as the STEGO.R package. A curated T cell atlas was built using STEGO.R from 12 prominent human studies, containing in total 500,000 T cells spanning multiple diseases, including melanoma, head-and-neck cancer, T-cell cancer, and lung transplantation, allowing the reanalysis of these datasets. The TCR-first approach was able to highlight dynamic features in hyperexpanded clones and treatment-specific changes, which were missed in the original GEx-first analyses. This meta-analysis also revealed previously unknown public T-cell clusters with common gene signatures and antigen specificities. Overall, adopting the TCR-first approach revealed T-cell features often missed by conventional GEx-focused methods and the STEGO.R tool facilitates this paradigm shift.
Competing Interest Statement
BO, KL and PM hold shares in ImmuneWatch BV, an immunoinformatics company, which developed IMW DETECT.
Footnotes
The first version of the paper focused on the STEGO.R tool development. While, the updated manuscript was written to reflect the recommended dogma changes from a gene expression (GEx)-first approach to a T cell receptor (TCR)-first method.