New findings from the NIH 4D Nucleome program extended spatial epigenomics with body-wide and disease-focused single-cell multi-omics studies, including multi-tissue efforts that map 3D genome folding alongside DNA methylation. Researchers reported that simultaneous measurement can reveal cases where genome architecture and methylation patterns diverge at the cell-type level. Separate 4D Nucleome-linked analyses expanded neurodegeneration biology, connecting changes in genome folding and epigenetic reprogramming in the Alzheimer’s brain to altered gene regulation. Tools used in the work included single-cell multiomics methods and AI models to integrate sequence and 3D features for cell-type-specific gene activity. For the biotech sector, the program’s emphasis on high-resolution, cell-resolved regulatory layers provides new datasets and modeling approaches that can feed target discovery, biomarker development, and mechanism studies across chronic diseases.