BOSTON (November 10, 2015) – Boston Children’s Hospital announced today at the Global Pediatric Innovation Summit + Awards (#PedInno15) the results of its international CLARITY Undiagnosed Challenge. In this genomics competition, 26 registered teams from seven countries sought to interpret DNA sequences and provide information to five families about conditions that had eluded diagnosis despite multiple doctor visits, tests and genetic studies.
The winning team, Nationwide Children’s Hospital (Columbus, OH), was awarded $25,000. Invitae Corporation (San Francisco) and Wuxi NextCODE Genomics (Cambridge, MA) were named runners-up.
CLARITY Undiagnosed is the second crowd-sourcing competition hosted by the Manton Center for Orphan Disease Research at Boston Children’s and the Department of Biomedical Informatics (DBMI) at Harvard Medical School. Submissions were evaluated by an independent, diverse panel of judges, including medical geneticists, computer scientists, bioinformaticians and clinical experts. Twenty-one of the original 26 teams ultimately completed the challenge.
While the first CLARITY Challenge, in 2012, emphasized the technical aspects of genomic sequencing, CLARITY Undiagnosed focused on the teams’ ability to interpret DNA sequence data and medical information and return clinically useful reports to doctors and families.
“The three top teams produced reports that were easy to follow, had results that made sense from a clinical point of view and presented the key information on the first page, so clinicians and families wouldn’t have to go digging,” says Alan Beggs, PhD, co-organizer of the Challenge and director of Boston Children’s Manton Center. “The judges valued reports that clearly stated the reasons for reporting a genetic variant and provided guidance to physicians. Nationwide Children’s took the extra step of providing a genetic counseling letter with each family’s report.”
“The key to our approach to the CLARITY Undiagnosed Challenge was the diversity of the team we assembled, which included genomic researchers, bioinformaticians, big data informatics experts, genetic counselors, medical geneticists and clinicians,” said Peter White, director of the Biomedical Genomics Core at Nationwide Children's Hospital. “The CLARITY Undiagnosed Challenge was a fantastic learning experience for all of us. We plan to make this collaborative approach the model for how we solve genomics challenges in our own patients at Nationwide Children’s Hospital.”
Beggs announced the results at Boston Children’s Global Pediatric Innovation Summit + Awards together with Catherine Brownstein, MPH, PhD, manager of the hospital’s Molecular Genomics Core Facility.
Despite the best efforts of a broad range of teams, no new “smoking guns” to explain the patients’ illnesses were discovered through the Challenge, although several families received confirmations of previous genetic findings and had others ruled out. New potential disease genes, or novel genetic variants, were identified for several of the families, leading to plans for new avenues of investigation and further studies to show whether the variants are really disease-causing.
“The patients in this Challenge were the toughest of the tough,” notes Beggs. “In general, when patients with genetic conditions have their genomes sequenced, about two thirds of those cases don’t get solved. Although their conditions are likely genetic in origin, there is no guarantee that a single primary genetic cause can be found for each family, and all have already undergone a lengthy diagnostic odyssey by expert clinical teams. Genomic sequencing is still a new area, but as we gain more experience with these tough cases, we can build a database and begin to see patterns emerging.”
Challenge co-organizer Isaac Kohane, MD, PhD, chair of the DBMI at Harvard Medical School, notes that bringing multiple multidisciplinary teams together around difficult medical questions could become the new paradigm for approaching rare diseases. Kohane, Beggs and Brownstein are all part of the National Institutes of Health’s Undiagnosed Diseases Network, which has pioneered the concept of intensive multidisciplinary approaches combining clinical and molecular studies to diagnose rare and difficult medical conditions.
“Medicine as it is practiced today is, at best, a series of solo performances; it’s not a group of individuals working together to solve a problem at the same time,” Kohane says. “If you want to see many doctors you have to go to many places, and if you want to see many experts, often you have to go to many cities and get repeatedly poked and prodded. Instead, we could bring many teams, many doctors, many researchers to the patient so they get the benefit of all those medical opinions without the trauma, heartbreak and cost.”
“Some patients may have a combination of predisposing genes, or they could have a type of mutation that sequencing can’t identify, such as a chromosomal rearrangement or copy number loss,” says Beggs. “In addition, environmental factors may play important roles in some of these patients.” To address these, and related questions, all five families will have the opportunity to enroll with the Manton Center to follow up on their results and pursue further answers.
For detailed information on the families and their results, contact Boston Children’s CLARITY team.
The 21 teams that completed the CLARITY Undiagnosed Challenge, in alphabetical order:
- Bina Technologies (Redwood City, CA)
- Clinical Institute of Medical Genetics (Ljubljana, Slovenia)
- Codified Genomics, LLC (Houston, TX)
- Emory University School of Medicine (Atlanta, GA)
- Geisinger Health System (Danville, PA) and SimulConsult (Chestnut Hill, MA)
- Gene.us (Austin, TX)
- Genomatix Software GmbH (Munich, Germany)
- Institute for Systems Biology (ISB) (Seattle, WA) and Inova Translational Medicine Institute (ITMI) (Falls Church, VA)
- intelliseq (Krakow, Poland)
- Invitae Corporation (San Francisco, CA) RUNNER UP
- Miti Medicine Inc. (Cambridge, MA)
- Nationwide Children’s Hospital (Columbus, OH) WINNER
- QIAGEN (Redwood, CA)
- Rare Genomics Institute (Hanover, MD)
- Seven Bridges Genomics (Cambridge, Massachusetts)
- SNPedia (Potomac, MD)
- Stanford University (Stanford, CA)
- University of Southern California (Los Angeles, CA)
- University of Utah (Salt Lake City, UT)
- Tel Aviv University (Tel Aviv, Israel), and Variantyx Ltd (Ashland, MA)
- WuXi NextCODE Genomics (Cambridge, MA) RUNNER UP
The CLARITY team is grateful to longtime hospital donor Rob Hale, CEO of Granite Telecommunications, his wife Karen and their family, who made the Challenge possible.
Full information about the Challenge is available online at http://www.childrenshospital.org/clarity-undiagnosed.
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