Longitudinal single cell multi-omic profiling of Nicaraguan children reveals trajectories of pediatric immune development and variation 2840

Abstract Description The state of the immune system varies widely within individuals over time and between populations. These variations make it difficult to predict the response to infection, vaccination, and other stimuli. Recent studies have begun to highlight how age, sex, genes, and environment shape the immune system, but a more quantitative understanding of how each of these factors contributes to immune variation is still lacking, particularly in children and in low- and middle-income countries. We previously generated a large-scale longitudinal blood transcriptomic dataset from a long-standing pediatric cohort study in Nicaragua with bulk RNA-Seq data on 679 blood samples from 115 healthy children sampled each March for six consecutive years in 3 overlapping age cohorts (ages 1-5 or 2-6, 5-10 and 9-14), and dissected the source and structure of gene expression variation. Here, we performed single-cell CITE / TCR / BCR and ATAC-Seq profiling for 16 representative individuals and integrated the results. We observe age-dependent trends across the multi-omic layers some of which were attributable to immune cell populations. Nevertheless, for most genes this was dominated by subject-specific patterns of expression, even after controlling for sex. Ultimately, we identify a set of interferon-related genes that decrease dramatically in early life and demonstrate that certain signatures predictive for vaccine responses and immunity show increasingly large amounts of individuality as children age. Topic Categories Computational and Systems Immunology (COMP)