Grammar of the Genome: Reading the Influence of DNA on Disease
The human genome has long been a difficult book to read. Modern technological advances have recently opened doors for researchers to begin asking a big question: What parts of our DNA sequences might influence disease? Mary Lauren Benton, Ph.D., recently joined the Baylor Engineering and Computer Science faculty as an assistant professor of bioinformatics, and she is working to answer that question.
“If you think of the genome like an instruction manual, I’m interested in the grammar,” Benton said. “I’m interested in understanding how short DNA sequences turn genes on and off in different cells and allow for many different outcomes. If we know how a particular sequence influences risk of heart disease, for example, we can use that information to help us guide clinical decisions, whether that’s applying different treatments, prescribing different medications or scheduling more preventative care. All of these things can help clinicians to better prioritize and care for patients.”
Benton uses computer modeling to look through large data sets of genetic information. Bioinformatics allows for processing of these large data in ways not possible previously, giving room for biological researchers to find patterns and solutions using methods and tools from computer science.
“I think of bioinformatics as the intersection of computer science and biology,” Benton said. “I take tools and methods from computer science, and I apply them to solve fundamental biological questions. We have a lot of really big data sets in biology. The human genome is 3 billion base pairs long, which we can’t analyze by hand. The tools from computer science and statistics give us a way to ask questions that we wouldn’t be able to otherwise. They open the doors to analyses that would have been impossible even 10 or 20 years ago.”
Benton most recently authored “The Influence of Evolutionary History on Human Health and Disease,” which was published in the Nature Reviews Genetic Journal and takes a look at the evolutionary origins of disease. Being diagnosed with a disease or health problem may feel like a present problem; however, Benton explained that looking at the foundations of a disease is important to understanding how to move forward with treatment.
“The foundations and the systems that are involved in disease have really deep evolutionary origins,” she said. “Cancer might be something that you’re diagnosed with today, but the foundation of cancer can be traced back to the idea that we have cells that are able to grow and divide, which also provides the opportunity for tumors to grow.”
Benton explained that it’s important to consider the history of the disease and the systems involved alongside any variants or environmental factors that help to cause the disease. A holistic understanding of disease can influence how patients are treated as well as provide information about how their diseases came to be.
“It’s not enough to understand what’s happening in a person right now or in the last five years,” Benton said. “Understanding the million-year history of how people got here is equally important to make advances in personalizing medicine, especially genomic medicine. Having that long lens is something that is often lost in the day-to-day operations of a doctor’s office.”
Benton is excited to be evaluating the way that researchers think about decoding genetic information. While a common approach is to think of genes as being able to be turned off or on with a simple “switch,” that may not be the most accurate approach.
“We study these sets of genetic switches and how they turn genes on and off at the right times. Often, we think about these switches working one-at-a-time; the gene is either on or it’s off,” Benton said. “But it is much more complicated than that. There are often multiple switches that act more like a dashboard of knobs and dials that all work together to properly tune the output of the genome.”
Benton’s research is moving toward the development of new models and ways of thinking about how known individual elements are combined and factored into this much larger, more accurate dashboard. Differences based on demographic histories, environmental variables and evolutionary processes all influence the risk of disease in different ways. A better understanding of genomes and how genetic variants relate to disease has major implications for precision medicine.
“It’s really vital for precision medicine to take into account the full diversity of the human experience. We can’t focus on one particular kind of person or one population. People of European ancestry are over-represented in genetic studies,” Benton said. “Improving diversity and representation in our genomic studies is vital to understanding how the genome relates to disease and to learning how to appropriately treat all of the patients that might walk through the doors of a clinic.”
Precision medicine, in some ways, seems futuristic and far-off. But, in other ways, precision medicine is already being used to protect at-risk individuals from diseases like cancer. While widespread precision medicine may not be seen for a long time, research like Benton’s plays a role in better understanding disease risk broadly and providing context for clinical solutions moving forward.
“Precision medicine is both happening right now and is something that we’ll probably always be working toward,” Benton said. “There are things that we understand right now about specific genetic variants that might predispose you to a certain kind of breast cancer, for example. We already have diseases that we can test for or treat differently based on someone’s genotype. But, because the genome is such a complicated thing, walking into the clinic and handing your DNA sequence to the doctor, who would then read it and prescribe the right treatments on the spot, is a goal that we’ll always be working toward. Still, I expect we’ll see big changes in the next five to 10 years given the current rate of progress.”