Diversity in immunogenomics: the value and the challenge

Abstract

Immunogenomics studies have been largely limited to individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations. Inclusion of a greater diversity of individuals in immunogenomics studies will substantially enhance our understanding of human immunology.

Targeted long-read sequencing facilitates phased diploid assembly and genotyping of the human T cell receptor alpha, delta and beta loci

“…The fact that we identified 79 undocumented (non-IMGT) alleles in only 9 unrelated individuals highlights the severe deficits that currently exist in germline databases. Considering our findings alongside other recent efforts underlines the work that remains to be done to fully catalog TR gene diversity in the human population (9,26). At present, the impact that these missing germline genes and alleles has on the analysis and interpretation of TCR repertoire sequencing studies is not clear, but would be expected to have profound effects on germline gene/allele assignment efforts, similar to what has been noted for IG repertoires.…”

“…While all samples contain novel alleles, samples with African ancestry contain the most novel alleles empirically (Figure 5). This is likely due to both more genetic variation found within African populations and the underrepresentation of African samples in immunogenomic databases(20, 26).…”

Commentary on Population matched (pm) germline allelic variants of immunoglobulin (IG) loci: relevance in infectious diseases and vaccination studies in human populations

“…Germline sequences differ substantially between subjects, and alleles found in some populations may be absent in others. Existing databases are likely biased towards alleles found in European populations and may lack many sequences found in understudied populations [ 2 ]. Improved, properly designed and curated germline gene databases are therefore needed for analysis of antibody repertoires.…”

A Pan-Cancer Analysis of Tumor-Infiltrating B Cell Repertoires

“…Additional analysis using datasets with both tumor and healthy samples would be informative for validating the results of this study. Moreover, the TCGA dataset, like many adaptive immune receptor repertoire sequencing (AIRR-seq) datasets ( 73 ), is primarily comprised of individuals with European ancestry ( 74 ). Including more individuals with non-European ancestry in immunogenomic studies is critical to understanding population differences in the adaptive immune system and improving precision immunodiagnostics and therapeutics.…”