Remarkable genetic advances over the last decade enabled researchers to map and identify each of the 25,000 or so genes that we all carry. But in spite of this pioneering work, scientists still don’t know what one-third of these genes do.
At OMRF, Jonathan Wren, Ph.D., is working to change that.
Wren is not your typical medical researcher. Instead of using microscopes and test tubes for his biological sleuthing, his lab relies on sophisticated computers to tease out clues that others may have missed.
“We try to make sense of the ‘data deluge’ by finding patterns within large databases and using different sources of information to identify relationships buried within the data,” said Wren. “Based on this information, we make predictions about the function of genes whose roles are unknown.”
Wren then teams with more “stereotypical” scientists—the kind who work with cells in laboratories—to test his hypotheses. These collaborative efforts, which often involve other researchers at OMRF, have already led to experiments testing the predicted functions of dozens of these unknown genes in the lab.
Together, these projects have unmasked genes from within this mysterious unknown third that play important roles in immune cell movement, coagulation, breast cancer progression, DNA repair and cell division.
“It’s like treasure hunting,” he said. “Large-scale genetic experiments churn out all sorts of information that has gone unused. What we’ve done is figure out a way to find some of the hidden nuggets.”
For example, when researchers conduct an experiment to study how genes react when a patient has cancer, they are looking for big results—giant spikes of activity connected to disease. But that work also generates a lot of additional data that, says Wren, might otherwise be ignored.
Using a computer program he wrote, called GAMMA, Wren mines this “throw away” data for statistically significant patterns—subtle links that might otherwise have gone unnoticed. “Genes tend to work in groups, so we can go through the results of other studies and find out how some unknown genes are related to genes that have already been studied,” he said.
One of Wren’s first experiments with GAMMA was in conjunction with OMRF scientist Gary Gorbsky, Ph.D. Using the computer program, Wren predicted that a formerly unknown gene, now called SKA3 because of this work, played a role in pulling chromosomes apart during cell division, an important factor in cancer.
Gorbsky, a biologist whose work focuses on cell division, was at first skeptical of Wren’s prediction. But when he ran experiments in the lab to study this previously unresearched gene, Wren’s theory proved true.
“It turned out to be a big discovery,” Wren said. “And that information led to the discovery of two other related genes.”
Wren is also collaborating with OMRF scientist Rheal Towner, Ph.D., to help pinpoint genes that are specific to brain tumors and, consequently, have strong potential for diagnostics and treatment.
Going forward, Wren will continue his cyber-detective work on the function of thousands of other mystery genes. “We’ll keep pushing the boundaries of what we know about human genetics until, hopefully, the ‘final third’ of our genome will no longer be a mystery,” he said.
