Scientists at Gladstone Institutes and Arc Institute built an AI tool that just rewrote the textbook on how DNA gets stored in cells. The tool, called IDLI, showed that over 85% of nucleosomes (those spool-like protein clusters that wrap DNA) contain sections of partially accessible DNA. That contradicts the long-held assumption that DNA is either locked away tight or fully exposed. "The conception before was that, when it came to nucleosomes, genes were either turned on or off, but we're finding it's more like a volume dial," says Gladstone investigator Vijay Ramani, PhD, who co-led the study published in Nature.
IDLI builds on an earlier technology called SAMOSA, which mapped nucleosome locations along individual DNA molecules. The new AI model goes deeper. It scans sequencing data in two dimensions to probe what's happening inside each nucleosome. The team found 14 distinct structural states of nucleosomes, each tied to different levels of gene activity. They also showed that transcription factors (proteins that control gene expression) directly shape those structures. Remove certain transcription factors, and the distortion patterns shift in predictable ways.
The underlying concept isn't new. Epigeneticists have known since the late 1980s that gene regulation operates on a spectrum. What IDLI delivers is resolution, the ability to actually measure these states at scale.
That matters. Complex diseases like cancer and neurodegeneration likely arise from small shifts across many genes. Ramani sees these 14 nucleosome states as a readout for those shifts. "Most complex diseases revolve around gradation; maybe a gene is on but at half the level it would normally be, or maybe it's on in the wrong cell type," he explains. Arc Institute, backed by $650 million from donors including Stripe CEO Patrick Collison, exists to fund this kind of long-horizon work without the usual grant-chasing grind.
Whether IDLI leads to therapeutics is anyone's guess. For now, researchers have 14 new dials to watch.