In the U.S. alone, an estimated 30 million Americans suffer from a rare disorder. Many of them never receive a diagnosis, and often find themselves on a lonely journey, going from doctor to doctor and test to test, sometimes for many years, with no explanation for their symptoms.
How many people fall in the “undiagnosed” category is unclear, but in its first six years, the NIH’s Undiagnosed Diseases Program has received more than 10,000 inquiries. Without a diagnosis, it’s often difficult to qualify for insurance coverage, receive coordinated care or even connect with a support group.
What if the work of solving these medical mysteries could be crowd-sourced? That’s the goal of CLARITY Undiagnosed, an international challenge launching today in which scientific teams can compete to provide answers for five families with undiagnosed conditions. (Deadline for applications: June 11).
Hosted by The Manton Center for Orphan Disease Research at Boston Children’s Hospital and the soon-to-be inaugurated Department of Biomedical Informatics (DBMI) at Harvard Medical School, CLARITY Undiagnosed will select up to 30 teams to compete. Each team will receive whole genome sequence data from each patient and key family members, as well as clinical summaries and, at the discretion of the families, short videos of the patients, who were identified through producers of a forthcoming documentary film, Undiagnosed. They’ll then have two months to interpret the data and try to provide answers.
“The CLARITY challenge will illuminate how far multidisciplinary teams with genomics, bioinformatics and clinical expertise can advance the diagnostic art if properly aligned,” says co-organizer Isaac Kohane, MD, PhD, professor of pediatrics at Boston Children’s Hospital and soon-to-be chair of the DBMI.
Best practices for genomic medicine
CLARITY—or the Children’s Leadership Award for the Reliable Interpretation and Appropriate Transmission of Your Genomic Information—was founded in 2012 to bring quality standards and best practices to genomic medicine. In its first Challenge, 23 teams competed to provide actionable genomic information for three patients with rare disease. The results, announced November 2012 and published in full in the journal Genome Biology in 2014, are described in this video:
CLARITY I underscored the variability from center to center in the quality of the clinical reporting and the need for medical expertise to bring meaning to the DNA findings. As a result, CLARITY Undiagnosed will focus less on the technical “pipeline” elements of sequence analysis—which have steadily improved and matured—and more on teams’ ability to provide clear, actionable results for the patients and families. Scoring will consider the thinking process, scientific knowledge, clinical relevance of the findings and, yes, the clarity of communications to the doctor and patient.
“We are moving into an era where understanding the meaning of vast amounts of new genomic information is our greatest hurdle,” says Alan Beggs, PhD, director of the Manton Center and a co-organizer of the Challenge.
Boston Children’s will almost certainly apply that knowledge in its collaboration with NIH’s Undiagnosed Diseases Network (UDN). Last year, the hospital became part of the Harvard Center for Integrated Approaches to Undiagnosed Diseases, one of six new clinical UDN sites around the country.
By 2017, teams of experts at the center’s three hospitals will enroll 50 patients per year, both children and adults, providing detailed clinical evaluations, genetic and genomic analysis, environmental exposure analysis, proteomics and metabolomics analysis, systems biology and network medicine analysis. All patients will be able to receive specialty care and clinical counseling while the team works to solve their diagnostic mystery.
“In the near future, we will do a lot better to bring our patients to the right doctors with all their clinical data and to provide a better interpretation of their whole genome,” says Kohane. “CLARITY Undiagnosed and the UDN will both point the way to how to do this.”