Defining T cell clonality from RNA-seq

In a recent collaboration with Greg Hapgood and Kerry Savage, we have shown that shallow RNA-seq data is sufficient to identify cell populations that contain T cell clonal expansions.

This work extends our efforts to extract T cell receptor sequences from RNA-seq. In our initial paper, we attempted to find T cell receptor sequences using RNA-seq on solid tumors. The T cells were a rare cell type, and thus the T cell receptor transcripts were also rare, contributing to the overall low yield. In the present study, we are looking at RNA-seq on sorted T cell populations, enabling us to greatly increase our yield.

Using only shallow RNA-seq (~80 samples pooled on a single HiSeq lane) we were clearly able to distinguish control samples (containing a diverse polyclonal population of T cells) from aberrant samples (an aberrant immunophenotype was observed in the cell surface markers, and all cells appeared to share the identical T cell receptor, signifying they are clonally expanded and likely malignant). Perhaps most interesting is the subset of cases which appeared immunophenotypically normal, yet clearly contained a clonally expanded population of cells by T cell receptor analysis, demonstrating the increased sensitivity of RNA-seq over flow cytometry.

Read more about it here: https://academic.oup.com/bioinformatics/article/2918631/Defining-the-clonality-of-peripheral-T-cell