Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)

Integrating T cell sequences and gene expression profiles uncovers functional subsets in single-cell datasets. Links between T cell clonotypes, as defined by T cell receptor (TCR) sequences, and phenotype, as reflected in gene expression (GEX) profiles, surface protein expression and peptide:major histocompatibility complex binding, can reveal functional relationships beyond the features shared by clonally related cells. Here we present clonotype neighbor graph analysis (CoNGA), a graph theoretic approach that identifies correlations between GEX profile and TCR sequence through statistical analysis of GEX and TCR similarity graphs. Using CoNGA, we uncovered associations between TCR sequence and GEX profiles that include a previously undescribed 'natural lymphocyte' population of human circulating CD8(+) T cells and a set of TCR sequence determinants of differentiation in thymocytes. These examples show that CoNGA might help elucidate complex relationships between TCR sequence and T cell phenotype in large, heterogeneous, single-cell datasets.

Automated summary

Integrating T cell sequences and gene expression profiles uncovers functional subsets in single-cell datasets, revealing relationships between TCR sequences and phenotypes. The CoNGA approach identifies correlations between TCR sequence and GEX profiles through statistical analysis, helping elucidate complex relationships in large single-cell datasets.