Recent advances in T-cell receptor repertoire analysis: Bridging the gap with multimodal single-cell RNA sequencing

Abstract

T cells exercise a multitude of functions such as cytotoxicity, secretion of immunomodulating cytokines or regulation of tolerance, collectively resulting in an effective control of immune-related disease. Through the unique mechanism of V(D)J recombination, T cells express a highly specific receptor complex known as the T-cell receptor (TCR). Single-cell sequencing technologies have paved the road for interrogating the transcriptome and the paired αβ TCR repertoire of a single T cell in tandem. In contrast, conventional bulk methods are restricted to only one layer of information. This combination of transcriptomic- and repertoire information can provide novel insight into the functional character of T cell immunity. Recently, single-cell technologies have gained in popularity due to improvements in throughput, decrease in cost and the ability for multimodal experiments that integrate different information layers. Consequently, this prompts the need for the development of novel computational tools that integrate transcriptomic profiles and corresponding features of the TCR repertoire. Here we discuss the current progress in the field of single-cell T cell sequencing, with a focus on the multimodality of new approaches that allow the paired profiling of cellular phenotype and clonotype information. In addition, this review provides detailed descriptions of recent computational developments for analyzing single-cell TCR sequencing data in an integrative manner using novel computational approaches. Finally, we present an overview of the available software tools that can be used to perform integrative analysis of gene expression and TCR profiles.