Institute of Information Science, Academia Sinica

Gene regulatory circuits among different cell types, environmental conditions and disease states are extremely complex, our current understanding of the circuitry is still in its infancy. We utilized natural occurring variability between individual humans and individual cells as a perturbation tool to dissect the gene circuitry. The vast majority of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. We analyzed Assay for Transposase-Accessible Chromatin (ATAC-seq) profiles from the activated primary CD4⁺ T cells of 105 healthy donors to identify ATAC-QTLs: genetic variants that affect chromatin accessibility. We found that ATAC-QTLs are widespread, disrupt binding sites for transcription factors known to be important for CD4⁺ T cell differentiation and activation, overlap and mediate expression QTLs from the same cells and are enriched for SNPs associated with autoimmune diseases. In another study, we utilized single-cell ATAC-seq to study epigenetic variability between individual dendritic cells during pathogen response.