Every cell in your body contains the same genetic sequence, yet each cell expresses only a subset of those genes. These cell-specific gene expression patterns, which ensure that a brain cell is different from a skin cell, are partly determined by the three-dimensional structure of the genetic material, which controls the accessibility of each gene.

MIT chemists have now come up with a new way to determine those 3D genome structures, using generative artificial intelligence. Their technique can predict thousands of structures in just minutes, making it much speedier than existing experimental methods for analyzing the structures.

Using this technique, researchers could more easily study how the 3D organization of the genome affects individual cells’ gene expression patterns and functions.

“Our goal was to try to predict the three-dimensional genome structure from the underlying DNA sequence,” says Bin Zhang, an associate professor of chemistry and the senior author of the study. “Now that we can do that, which puts this technique on par with the cutting-edge experimental techniques, it can really open up a lot of interesting opportunities.”

MIT graduate students Greg Schuette and Zhuohan Lao are the lead authors of the paper, which appears today in Science Advances.

From sequence to structure

Inside the cell nucleus, DNA and proteins form a complex called chromatin, which has several levels of organization, allowing cells to cram 2 meters of DNA into a nucleus that is only one-hundredth of a millimeter in diameter. Long strands of DNA wind around proteins called histones, giving rise to a structure somewhat like beads on a string.

Chemical tags known as epigenetic modifications can be attached to DNA at specific locations, and these tags, which vary by cell type, affect the folding of the chromatin and the accessibility of nearby genes. These