Ancestral Diversity is Limited in Published T Cell Receptor Sequencing Studies.

The emergence of high-throughput sequencing techniques and the development of bioinformatics tools provide efficient ways to profile the human adaptive immune receptor repertoire (AIRR) including repertoires of T cell receptors (TCRs) and immunoglobulins ( Bradley and Thomas, 2019 Bradley P. Thomas P.G. Using T Cell Receptor Repertoires to Understand the Principles of Adaptive Immune Recognition. Annu. Rev. Immunol. 2019; 37: 547-570 Crossref PubMed Scopus (51) Google Scholar ). Despite these advancements, the representation of populations in the AIRR sequencing (AIRR-seq) studies remains unknown. AIRR data from populations with diverse genetic ancestry could potentially elucidate genomic and phenotypic similarities or differences in the human immune system and immune-related diseases across populations ( Peng et al., 2021 Peng K. Safonova Y. Shugay M. Popejoy A.B. Rodriguez O.L. Breden F. Brodin P. Burkhardt A.M. Bustamante C. Cao-Lormeau V.M. et al. Diversity in immunogenomics: the value and the challenge. Nat. Methods. 2021; 18: 588-591 Crossref PubMed Scopus (11) Google Scholar ). It was previously demonstrated that the majority of the participants in genome-wide association studies (GWASs) were of European ancestry ( Peterson et al., 2019 Peterson R.E. Kuchenbaecker K. Walters R.K. Chen C.Y. Popejoy A.B. Periyasamy S. Lam M. Iyegbe C. Strawbridge R.J. Brick L. et al. Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations. Cell. 2019; 179: 589-603 Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar ). However, the level of ancestral diversity in AIRR-seq stand is not clear and has not been studied in detail ( Peng et al., 2021 Peng K. Safonova Y. Shugay M. Popejoy A.B. Rodriguez O.L. Breden F. Brodin P. Burkhardt A.M. Bustamante C. Cao-Lormeau V.M. et al. Diversity in immunogenomics: the value and the challenge. Nat. Methods. 2021; 18: 588-591 Crossref PubMed Scopus (11) Google Scholar ). To address the emerging issue of the lack of diversity in immunogenomics studies described in our previous work ( Peng et al., 2021 Peng K. Safonova Y. Shugay M. Popejoy A.B. Rodriguez O.L. Breden F. Brodin P. Burkhardt A.M. Bustamante C. Cao-Lormeau V.M. et al. Diversity in immunogenomics: the value and the challenge. Nat. Methods. 2021; 18: 588-591 Crossref PubMed Scopus (11) Google Scholar ) and to further develop a strategic roadmap to engage diverse populations in AIRR-seq studies and highlight this issue for the community, we investigated the ancestral diversity (AD) in TCR sequencing (TCR-seq) studies currently reported in published studies and databases. We also discuss the challenges and opportunities of including underrepresented populations in TCR-seq research and how this information may guide future efforts to increase diversity in the field of immunogenomics.