NIH’s 4D Nucleome program delivered a new set of insights on how spatial chromatin structure and DNA methylation regulate gene expression across health and disease. Across eight papers published in Science and Science Advances (from the July 23 release), teams used single-cell multi-omics approaches to map noncoding genomic changes in conditions including heart disease, Alzheimer’s disease, brain aging, retinal health, and immune cell development. The research demonstrates how multi-layer data can connect three-dimensional genome organization to functional gene regulation, providing new candidate regulatory mechanisms and targets for downstream therapeutic exploration. For biotech, the practical value is a clearer framework for prioritizing regulatory elements and interpreting disease-associated noncoding signals, especially where traditional genomics offers limited biological context. As 4D Nucleome data mature, companies will be able to incorporate spatial and epigenomic context into target discovery and mechanism-focused programs.