NIH’s 4D Nucleome program delivered a new wave of spatial and epigenomic findings across eight papers published in Science and Science Advances. The studies apply single-cell multi-omics to map how chromatin architecture and DNA methylation coordinate gene regulation in health and disease. The publications span heart disease, Alzheimer’s, brain aging, retinal health, and immune cell development, using tools from the program’s earlier phase to track changes in the noncoding genome. Researchers also framed the results as a step toward understanding which genome organization states correspond to disease phenotypes. The output expands the platform-grade knowledge base for biotech translation—especially for companies building targeting hypotheses around epigenetic state changes and spatial genome features rather than single-gene biomarkers.