New tool to help advance research into genetic cause of cancer

Researchers have recently developed a new mathematical model that allows scientists to take a closer look at genetical material known as chromatin, that plays a critical role in directing the activity of genes.

The study, published in Nature Communications, was led by Chongzhi Zang, PhD, a health researcher at the University of Virginia Health System in Charlottesville, Virginia. Recent technology has allowed scientists to study chromatin within individual cells, however, this tool, known as single-cell ATAC-seq, generates an excess of data that’s unnecessary and biased. According to Zang and his team of researchers, their tool eliminates the unneeded information while ensuring the integrity of the data.

According to the study, chromatin, a combination of DNA and protein, is the building block of chromosomes, and helps direct the activity of genes. When something is wrong with chromatin, it can lead to cancer and other diseases.

For his mathematical model, Zang used a model from number theory and cryptology named simplex encoding and used it to code DNA sequences into mathematical forms to simplify the complex genome. Next, he compared the simplified form with other coded DNA sequences to identify the bias and unnecessary information in the sequence data.

“The DNA sequences’ complexity increases exponentially when they get longer. They are difficult to model because a typical dataset has millions of sequences from thousands of cells,” said Shengen Shawn Hu, PhD, a research scientist in Zang’s lab. “But the simplex encoding model can give an accurate estimation of sequence biases because of its beautiful mathematical property.”

Testing of the tool suggested that it was significantly better at analyzing complex single-cell data to characterize different cell types than conventional methods, which could help doctors detect tiny numbers of disease cells within much larger specimens and better diagnose disease.

“We hope this tool can benefit the biomedical research community in studying chromatin biology and genomics, and eventually help disease research,” Zang said. “It is always exciting to see our peers use the tools we developed to make important scientific discoveries in their own research.”