Chongzhi Zang, PhD, is director of computational genomics at UVA Cancer Center and a member of UVA’s Departments of Genome Sciences; Biochemistry and Molecular Genetics; and Biomedical Engineering.
School of Medicine scientists have developed a new tool that could help reveal genetic causes of cancer, predict patient outcomes and improve care for not just cancer but many other diseases where genes go haywire, such as autoimmune disorders and neurodegenerative conditions.
The innovative method, developed by UVA’s Chongzhi Zang, PhD, and colleagues, is helping scientists understand powerful controllers of our gene activity known as “transcriptional condensates.” These condensates are tiny droplet-like structures filled with proteins that form on our DNA like dew on grass. Normally, they can help activate our genes exactly when needed, which is vital for healthy cell function. But when these droplets form improperly, they can drive faulty gene activity leading to cancer and many other diseases.
How these condensates form and their precise role in gene regulation has been a mystery, but Zang’s pioneering research, using advanced data science approaches, is offering important insights. Further, the scientists found they could use their new method to analyze large-scale genetic data to predict outcomes for patients with breast and colon cancer, potentially paving a way towards precision medicine.
“For the first time ever, we uncovered the connection between DNA patterns and the formation of these transcriptional condensates,” said Zang, director of computational genomics at UVA Cancer Center and a member of UVA’s Departments of Genome Sciences; Biochemistry and Molecular Genetics; and Biomedical Engineering. “This breakthrough can help us better understand what causes diseases and moves us closer to developing new diagnostic tools and therapies.”
Powerful Insights into Gene Regulation
Scientists have had a very murky understanding of how transcriptional condensates form and operate within our cells. They’ve known that these droplets form when specific proteins, such as those essential controllers of gene activity called “transcription factors,” gather near our DNA. But exactly why and how this condensation occurs has been unclear.
To find answers, Zang and his team created an innovative computational method to analyze a broad swath of DNA data and looked at different ways transcription factors interact with DNA in our cells. Using their new metric, they determined that certain regions of our DNA that are critical for controlling gene activity often form special clusters populated by transcription factors with biophysical properties for condensation. These clusters, the scientists believe, are key for the formation of transcriptional condensates, influencing gene activity in both health and disease.
Based on their research, the scientists believe that their discoveries could improve cancer care by providing a better understanding of the different types of condensates associated with various cancers. In a new paper outlining their findings, they say that further exploration in this area could become an important “stepstone” for precision medicine. By targeting transcriptional condensates or the factors that contribute to their formation, doctors one day may be able to better battle a wide array of diseases where our genes go awry.
“Our work opens a new path towards understanding these important biomolecular condensates through computational genomics and data science,” Zang said. “It is a small but meaningful step forward in unraveling the mysterious workings of our genes and ultimately helping fight disease.”
Findings Published
The researchers have published their findings in the scientific journal Nucleic Acids Research. The research team consisted of Shengyuan Wang, Zhenjia Wang and Zang. The scientists have no financial interest in the work.
The research was supported by the National Institutes of Health, grant R35GM133712.
To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.
