Dynamic regulatory elements in single-cell multimodal data implicate key immune cell states enriched for autoimmune disease heritability.

ABSTRACT: In autoimmune diseases such as rheumatoid arthritis, the immune system attacks the body's own cells. Developing a precise understanding of the cell states where noncoding autoimmune risk variants impart causal mechanisms is critical to developing curative therapies. Here, to identify noncoding regions with accessible chromatin that associate with cell-state-defining gene expression patterns, we leveraged multimodal single-nucleus RNA and assay for transposase-accessible chromatin (ATAC) sequencing data across 28,674 cells from the inflamed synovial tissue of 12 donors. Specifically, we used a multivariate Poisson model to predict peak accessibility from single-nucleus RNA sequencing principal components. For 14 autoimmune diseases, we discovered that cell-state-dependent ('dynamic') chroma

SUBMITTER: Gupta A 

PROVIDER: S-EPMC10787644 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature