Decoding DNA’s Spatial Organization With Precision Tools

DNA is more than simply a lengthy string of genetic code; it is a complex three-dimensional structure folded inside each cell. That means that the equipment used to examine DNA must be as sophisticated, capable of reading not just the code itself but also its spatial arrangement.

Researchers at Case Western Reserve University evaluated several computer technologies for analyzing how DNA folds and interacts within individual cells. Their findings, published in Nature Communications, might help scientists better grasp how to read the body’s genetic “instruction manual” in various situations, such as determining what goes wrong when diseases develop or how cells alter their roles as individuals grow.

The 3D structure of DNA affects how genes interact with each other, just like the layout of a house affects how people move through it. Understanding this structure is crucial for figuring out how diseases develop and how we might treat them.

Fulai Jin, Professor, Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University

The researchers solved a critical issue: previous techniques for evaluating DNA structure frequently provided conflicting findings. He compared it to having numerous translators who disagree on the meaning of a foreign language text.

The researchers tested 13 software tools on ten datasets from mice and people and discovered that different computer tools perform better with different sorts of data. They also observed that modifying how data is processed before analysis might significantly enhance findings. Artificial intelligence computer programs do particularly well with low-quality and complicated datasets.

“We’re essentially helping scientists find or build better microscopes to see how DNA works inside individual cells. This could lead to a better understanding of genetic diseases and potentially new treatment strategies,” Jin added.

Jin stated that the new methods might enable scientists to understand which genes are turned on or off in diseased cells, explain why treatments work for some patients but not others, and observe how cells change during early development.

The study team also developed a software package that other scientists can use to determine the optimal way to analyze their specific research, much like a GPS program determines the best path to a destination.

Instead of researchers having to guess which tool might work best, our software can test multiple approaches and recommend the optimal one.

Fulai Jin, Professor, Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University

The approaches are publicly available to scientists worldwide via GitHub, an open-source platform that enables developers to build, store, manage, and distribute code. Jin believes that extensive accessibility has the potential to expedite discoveries across several sectors of biomedical research.

This is a significant step toward making sense of the massive genetic data from modern sequencing – and toward understanding how our genetic blueprint truly works.

Fulai Jin, Professor, Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University