Open AccessIntegrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)
Author(s) -
Stefan A. Schattgen,
Kate Guion,
Jeremy Chase Crawford,
Aisha Souquette,
Alvaro Martinez-Barrio,
Michael J.T. Stubbington,
Paul G. Thomas,
Philip Bradley
Publication year - 2021
Publication title -
nature biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.358
H-Index - 445
eISSN - 1546-1696
pISSN - 1087-0156
DOI - 10.1038/s41587-021-00989-2
Subject(s) - t cell receptor , biology , cd8 , gene , major histocompatibility complex , phenotype , t cell , genetics , sequence analysis , computational biology , microbiology and biotechnology , antigen , immune system
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.