Contest develops 'best practices' to use genome sequencing in patient care
Friday, November 9, 2012

A University of Iowa team of more than 30 researchers from five different colleges has been named a finalist and awarded $5,000 in a competition that challenged international research teams to provide the best interpretation and communication of DNA sequencing results for three children with rare, undiagnosed genetic diseases.

The CLARITY challenge, which was organized by Boston Children’s Hospital and launched in January 2012, pinpointed the genetic cause of one child's muscular condition and deafness, and identified a probable cause for heart rhythm disturbances in a second family. The first-of-its-kind contest also produced approaches that contest organizers hope will form the basis of much-needed “best practices” in genome analysis, interpretation, and reporting.

“As the cost of genome sequencing drops and its availability rises, patients are more likely to make use of this technology to learn how their genes affect their health,” says Richard Smith, M.D., director of Iowa Institute of Human Genetics at the UI. “But a huge challenge is how to help physicians and patients interpret the genetic data in ways that will improve patient care and protect patient privacy. This competition generated some really sound, innovative ways to use genomic sequencing in patient care safely, responsibly, and in a meaningful way.”

Brigham and Women’s Hospital, Division of Genetics in Boston, Mass., was named the winner of the contest and awarded $15,000. The UI team and a team based in Germany were each named finalists and awarded $5,000. The results were announced Nov. 7 at the American Society of Human Genetics (ASHG) annual meeting in San Francisco.

Participants in the competition ranged from small biotech startups to the National Institutes of Health, with teams based in the United States, Canada, China, India, Israel, Italy, Germany, the Netherlands, Singapore, Slovenia, Spain, Switzerland, and Sweden.

The UI multidisciplinary team led by Smith was organized into six sub-teams to analyze the clinical and bioinformatic data and to interpret and collate the results of the analysis: an advisory team; bioinformatics; clinical interpretation; counseling/genetic interpretation; electronic medical records; and variant research. The teams focused on different aspects of the problem but worked together to develop protocols for consenting patients, targeting the sequencing tests, interpreting the data, and returning the results to the patients.

Several aspects of the UI team’s approach earned them the “finalist” designation, including an approach to data analysis that incorporated an evaluation of data quality or coverage, the multidisciplinary team approach, and the consent form, which was considered the best in the competition as it allows patients to customize the type and scope of genetic information they will receive from the DNA sequencing data.

"When we analyze a patient’s genome, we will find secondary findings—genetic information not related to the condition that is the main focus of the testing. We decided that the patient was the best person to decide how much of that secondary information they should receive, and we developed a consent form that allowed them to do that," says Colleen Campbell, Ph.D., who led the counseling/genetic interpretation subgroup. Campbell also holds a Master of Science degree in genetic counseling and is a certified genetic counselor.

The UI consent form lays out several categories of information that patients can choose to receive based on the results of their DNA sequence, including whether they may respond negatively to a particular drug, if they carry a known disease mutation that could be inherited by their children, or if they have a mutation that will cause disease later in life, like Huntington's disease, where there is no treatment.

"This competition presented us with a significant challenge in terms of the scope and complexity of the genetic analysis and interpretation and the challenge of delivering genetic findings in a meaningful way," Smith says. "Our experience highlighted the importance of having a highly diverse, multidisciplinary team working together to accomplish those goals, and helped us develop a framework for how we could handle genetic testing for families in Iowa through the Iowa Institute for Human Genetics.”