SALT LAKE CITY - On the computer screen in front of him was the smoking gun responsible for the young child’s death. After analyzing the child’s DNA, Martin Tristani-Firouzi, M.D., a pediatric cardiologist at University of Utah Health who also practices at Primary Children’s Hospital, knew what caused his patient’s heart to seize. A large chunk of DNA was missing, disrupting a gene that controls the heart’s rhythmic beating.
Had he known earlier, he may have been able to tailor the child’s medical care to prevent the worst from happening.
Within our DNA is a treasure trove of health information that scientists have begun to decode but numerous hurdles have prevented genomics-based precision medicine from being routinely integrated into the clinic. With $3 million from the National Human Genome Research Institute (NHGRI), a team of researchers at U of U Health and Primary Children’s Hospital in Salt Lake City is taking personal genomics to the next step. They are developing a web-based app to assist doctors with providing clinical care based on information found within their patient’s DNA.
The software tool – called IOBIO – searches for changes in DNA, also called genetic variants, that contribute to a patient’s health condition. Knowing this information can help clinicians redefine the best course of treatment to meet their patient’s needs.
"We are lowering the barrier for clinicians to analyze and understand their patient's genomic information, and accelerate the application of precision medicine into the clinic," says the project’s lead investigator Gabor Marth, DSc, professor of Human Genetics at U of U Health and co-director of the USTAR Center for Genetic Discovery.
IOBIO aims to enhance the clinical utility of personal genomic analysis with the following features:
- Easy-to-use, intuitive, real-time interface
- Report-out of candidate disease variants and relationships to known diseases
- State-of-the-art protocols for data security
- Feedback on data quality issues that hinder analysis
- Guidance through “next steps” when no plausible candidate is found
There are significant barriers preventing precision medicine from being implemented into the clinic today. The complex nature of current genomic analysis tools means that physicians depend on bioinformatics experts to analyze genomic data. IOBIO is designed to leverage a physician’s medical insight by enabling them to critically evaluate results.
“We understand that health care providers have clinical knowledge that is invaluable for finding the potential cause of their patient’s disease,” says Marth. “That is why it is important to put these tools into the hands of providers.”
A second barrier is that physicians typically face a dead-end when analytic tools fail to turn up plausible candidate genes. IOBIO overcomes this hurdle by offering alternative courses of action. The tool guides users through next steps such as improving the quality of the data and suggesting strategies for expanding the search.
Physicians at U of U Health and Primary Children’s Hospital are working with bioinformaticists and computer scientists to design, prioritize and evaluate IOBIO’s features, and determine best practices for integrating genomic analysis into patient care.
In the first phase of development, clinicians are using the tool for guidance primarily in two types of patient cases. They are searching for DNA variations that could explain why children have died suddenly from hidden heart abnormalities. This information could be used to determine whether living family members have the same condition, and guide their care. Clinicians are also searching for genetic variations that could explain mysterious chronic health conditions that have no known cause.
“We are focused on getting precision medicine into the clinic,“ says Tristani-Firouzi. “We strongly believe that a model whereby physicians are offered a greater degree of granularity in their medical decision-making is crucial for the delivery of high quality and high value care.”
Following an iterative process of feedback and tool refinement, the research team will train a larger network of physicians, genetics counselors, and trainees to further optimize IOBIO and expand its use. Over the next four years, the goal is to incorporate IOBIO into clinical care in Pediatric Cardiology, Neurology, Gastroenterology, and Immunology.
The initiative is part of NHGRI’s Clinical Sequencing Evidence-Generating Research (CSER2) Consortium.