By Kevin Davies
August 16, 2012 | Boston Children’s Hospital has announced that 30 academic and commercial organizations have entered the CLARITY Challenge, a contest to identify the putative disease-causing mutations in three young patients currently being cared for at the hospital.
The goal of the CLARITY (Children’s Leadership Award for the Reliable Interpretation and Transmission of Your genomic information) contest is to not only provide a conclusive diagnosis for the three patients and their families, but more generally to establish guidelines and best practices for clinical genome interpretation.
The 30 CLARITY contestants have entered from all over the world, including North America, China, India, Israel, Italy, Germany, the Netherlands, Singapore, Slovenia, Spain, Switzerland and Sweden. They have about six weeks – until the deadline of September 30 -- to submit their reports.
The contest organizers -- Isaac Kohane (director of the hospital’s informatics program), David Margulies (executive director of The Gene Partnership at Boston Children’s Hospital), and Alan Beggs (director of the Manton Center for Orphan Disease Research at the hospital) -- hope to unveil the winners at the annual conference of the American Society of Human Genetics in November.
“We have far more entrants than I was expecting,” Kohane told Bio-IT World. “Internally we’d said we’d be happy with ten! What this showed me is that there’s a huge hunger for real data and real cases.” Kohane recalled a similarly positive response when he launched an earlier contest for natural language processing of electronic health records, which attracted 35 international teams to compete. “I’ve not forgotten that lesson – people want real cases, where the whole problem is encompassed by the challenge.”
The list of contestants includes some familiar names in the infancy of genome interpretation such as the Medical College of Wisconsin, the NIH, and BGI. Some emerging informatics companies are also entering, including Genomatix, NextBio, Omicia, and Strand Life Sciences.
But there are some notable absences, including four major genome centers – the Broad Institute, The Genome Institute at Washington University, Baylor College of Medicine and the Wellcome Trust Sanger Institute. Also absent are genome interpretation start-ups Personalis (or its Stanford academic founders), SVbio, and several other genome analysis informatics companies (CLCbio, Ingenuity, Partek, DNAStar etc).
Also absent are the companies that launched the direct-to-consumer genomics revolution in 2007-08 – 23andMe, Navigenics, Pathway Genetics and deCODE Genetics. “One consumer genomics company explored [entering the contest] but then withdrew for reasons that are opaque to me,” says Kohane.
As for the absence of any of the big four genome centers, Kohane says that a group in one large genome center wanted to compete. “However, we had to be fastidious about the rules, and one rule was your parent organization had to sign off on participation. For whatever reason, they didn’t get that approval.”
BGI, on the other hand, has formed a multi-disciplinary team within the organization to participate in the CLARITY competition, Xing Xu, BGI’s director of cloud computing, tells Bio-IT World. “The main purpose of our participation is to examine the capability of BGI to annotate human genomes for clinical related applications,” Xu says. “This will be a pilot study for us to integrate our internal resources, and we are glad to be chosen as one of the final contestant teams.”
Michael Cariaso, the co-developer with Greg Lennon of SNPedia and Promethease (a popular program for consumers to analyze their own genome variant results), decided to enter CLARITY. “My hope is that some of the information we provide might be useful to the patients and their families, and I think the contest model makes an interesting research project,” he said. “Normally we're working with data from healthy people, and there isn't always an interesting needle in the haystack. With CLARITY, we have three full genome family trios and there is a needle in every haystack. This has helped to focus our efforts, to improve the content in SNPedia, and the Promethease report interface.”
Kohane says the CLARITY Challenge is an attempt to “catalyze the development of de facto standards of integration and enshrine those best practices and standard… We decided as a group that this industry should not compete on safety. We need to be able to develop standards for the safe ferrying of information all the way to final interpretation.”
Kohane says the entering groups have been tasked to behave as if they were an actual diagnostics lab receiving a DNA sample to do the best they can. “Since we don’t know the right answer, we told all the contestants that the goal was not to solve the mystery of the patient,” he says. “That would be fantastic of course. But more important, there’s a process to bring together the end-to-end process that allows you to go from a clinically understandable report… and yet provide all the supporting documentation down to the process of assembling the reads and quality scores.”
“The entries will be judged not just on the final report but on all the supporting data, including genome assemblies, variant calling, the interpretation of single variants, and the report itself – not the answer but the actual comprehensibility and rational basis for the report. And then, as cherry on top, [whether] the diagnosis is believable.”
Top 30 List
The contest is being sponsored by Life Technologies and Complete Genomics, which have independently sequenced the genomes of the three patients. Boston Children’s will award a $25,000 prize to the winning research team, which will be selected by a 7-person judging panel.
The 30 teams have been provided with the raw DNA sequence data (whole-genome and exome sequences) and de-identified clinical data from three children and their immediate relatives identified by The Manton Center for Orphan Disease Research at Boston Children’s. Two of the three patients have an undiagnosed neuromuscular disorder, while the third has a cardiovascular problem. They have all tested negative for current genetic diagnostic tests.
"Traditional genetic tests examine our genes one by one, requiring doctors to have a good idea ahead of time which of our roughly 20,000 genes is the likely cause,” says co-organizer Alan Beggs. “The beauty of whole-genome sequencing is that it provides results for virtually all of our genes at once. The challenge for our contestants is to pick out that one disease-causing mutation from the vast numbers of genetic differences that make each of us unique.”
The 30 CLARITY Challenge contestants (in alphabetical order) are:
- BGI (Shenzhen, China)
- Brigham and Women's Hospital, Division of Genetics (Boston, Massachusetts)
- British Columbia Cancer Agency (Vancouver, Canada)
- Children's Hospital of Eastern Ontario (Ottawa, Canada)
- Clinical Institute of Medical Genetics (Ljubljana, Slovenia)
- Genedata AG (Basel, Switzerland)
- Genomatix (Munich, Germany), CeGaT (Tübingen, Germany), Institute of Pathology, University Hospital of Bonn (Bonn, Germany)
- Genome Institute of Singapore Agency for Science, Technology and Research (A*STAR) (Biopolis, Singapore)
- HudsonAlpha Institute for Biotechnology (Huntsville, Alabama)
- Institute for Systems Biology (Seattle, Washington)
- IRCCS Casa Sollievo della Sofferenza (San Giovanni Rotondo, Foggia, Italy)
- National Institutes of Health (Bethesda, Maryland)
- NextBio (Santa Clara, California)
- Omicia, Inc. (Emeryville, California)
- Pearlgen (Chapel Hill, North Carolina)
- Radboud University Nijmegen Medical Center (Nijmegen, Netherlands)
- Sanofi (Cambridge, Massachusetts)
- Science For Life Laboratory (SciLifeLab), Karolinska Institute (Solna, Sweden)
- Scripps Genomic Medicine, Scripps Translational Science Institute (San Diego, California)
- Seven Bridges Genomics (Cambridge, Massachusetts)
- SimulConsult / Geisinger (Chestnut Hill, Massachusetts / Danville, Pennsylvania)
- SNPedia (Potomac, Maryland)
- Strand Life Sciences (Bangalore, India)
- Tel Aviv University (Israel)
- The Medical College of Wisconsin (Milwaukee, Wisconsin)
- The Research Institute at Nationwide Children's Hospital (Columbus, Ohio)
- The University of Texas Health Science Center at Houston, The Brown Foundation Institute of Molecular Medicine (Houston, Texas)
- Universidad de Cantabria (Santander, Spain)
- University of Iowa (Iowa City, Iowa)
- Yale School of Public Health, Division of Biostatistics (New Haven, Connecticut)
Full information about the Challenge is available at www.childrenshospital.org/CLARITY