Click here to close now.




















Welcome!

News Feed Item

Boston Children's Hospital announces international genomics competition winner

Results will inform "best practices" for field where standards are lacking

SAN FRANCISCO, Nov. 7, 2012 /PRNewswire-USNewswire/ -- A first-of-its-kind international contest organized by Boston Children's Hospital, known as CLARITY, solves at least one family's genetic mystery while taking the first steps toward establishing "best practices" for using genomic sequencing in patient care safely, responsibly and in a meaningful way.

The contest winner, the Division of Clinical Genetics at Brigham and Women's Hospital, Boston, was one of 23 research groups competing to provide the best interpretation and communication of DNA sequencing results. Results were announced today at the American Society of Human Genetics (ASHG) annual meeting (Moscone Convention Center, hashtag #CLARITYDNA) and will be detailed in a forthcoming paper.

As testing costs go down, genomic sequencing is increasingly offered to patients, sometimes direct to consumer. Yet there haven't been standards for interpreting the voluminous DNA data, identifying actionable findings, communicating them to doctors and patients and dealing with unexpected, incidental findings.

"The community took this challenge very seriously, and we had tremendous participation," says CLARITY co-organizer David Margulies, MD, executive director of the Gene Partnership at Boston Children's Hospital. "We got the best thinking from around the world, and it has moved us toward a consensus on how to report sequencing data for use in the clinic."

The winning team was awarded $15,000. Two finalist teams were awarded $5,000 each: the University of Iowa and a German team comprised of Genomatix (Munich), CeGaT (Tubingen) and the Institute of Pathology at University Hospital of Bonn (Bonn).

Five additional teams received Special Mention for their contributions: the Clinical Institute of Medical Genetics (Ljubljana, Slovenia); The Research Institute at Nationwide Children's Hospital (Columbus, Ohio); Science for Life Laboratory (SciLifeLab) of the Karolinska Institute (Solna, Sweden); Scripps Genomic Medicine, Scripps Translational Science Institute (San Diego, Calif.); and a team comprised of SimulConsult (Chestnut Hill, Mass.) and Geisinger Health System (Danville, Pa.).

CLARITY's design

CLARITY (Children's Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information) was launched in January 2012. It challenged contestants to interpret DNA sequences from three children with rare conditions for which no genetic cause had been identified, selected by the Manton Center for Orphan Disease Research at Boston Children's Hospital. The children's identities were kept anonymous.

Of 40 research groups that submitted applications, 30 were selected to compete. Each received medical data for the three children and their parents, along with whole-genome and whole-exome sequences generated by contest sponsors Life Technologies Corporation and Complete Genomics.

Twenty-three teams went on to submit complete entries, reviewed by an independent panel of judges using predefined criteria. While many entries got high marks, the Brigham and Women's team was judged to have the best combination of cutting-edge bioinformatic analysis, clarity and utility of its clinical reports for the three families, and appropriate identification of the families' likely genetic defects. The two finalist teams were judged unique and outstanding in one or more areas; the Genomatix team was the only group to correctly flag every likely genetic mutation in all three families, while the University of Iowa team took unique approaches to returning unexpected genetic results based on patient preferences and indicating regions of low coverage or low confidence in their reports.

Answers for families

For one of the three families, CLARITY solved a mystery more than a decade old. Sixth-grader Adam Foye had undergone testing for every gene known to explain his type of muscle weakness, a condition called centronuclear myopathy, always with negative findings. He also has hearing impairment.

Eight of the 23 CLARITY contestants identified alterations in a gene called titin as the cause of Adam's muscle weakness, and six teams identified mutations in a gene called GJB2 as the likely cause of his hearing loss. These results were judged to be correct, and three teams made both identifications.

CLARITY co-organizer Alan Beggs, Ph.D., director of the Manton Center for Orphan Disease Research at Boston Children's, had independently identified titin mutations in four other patients with centronuclear myopathy by using whole-exome sequencing. "Even if we had suspected titin mutations in Adam, it's an enormous gene, and to sequence it individually, by hand, would have taken nine months in the lab, at a prohibitive cost," Beggs says. "That's why genomic sequencing is such a revolutionary technology."

Titin's involvement makes biological sense, Beggs adds, since its protein makes up part of the contractile structure in muscles. Beggs now plans to model the titin defect in zebrafish, allowing his team to do large-scale testing of potential drugs that might correct it.

"We've been celebrating, we've been waiting for an answer for 11 years," says Sarah Foye, Adam's mother. "It doesn't mean we know the treatment now, but it's pointing us in the right direction and we can cross other possibilities off the list."

The contest also identified a probable cause for heart rhythm disturbances in the second family, whose son Liam Burns died 12 days after birth: mutation of a gene called TRPM4, cited by seven teams as likely to be causative. In addition to rhythm disturbances, Liam and several other family members had structural heart defects that remain unexplained by CLARITY; Boston Children's researchers at The Manton Center are investigating whether the TRPM4 alterations are involved.

The genetic cause of the third child's disorder, another muscle-weakening disease known as nemaline myopathy, remains unclear. In all, seven genetic variants were cited by two or more contestants; four were judged worthy of further investigation, including variants of two genes never before associated with nemaline myopathy. The Manton Center at Boston Children's plans to explore these genes further to see if the variants are causative.

Guidance for best practices

There was considerable variability among the contestants' techniques and findings, to be described in the forthcoming paper. However, the teams that were finalists had methods and results that were sound and substantially similar, says Margulies.

"When these best practices are disseminated, skilled practitioners around the world will be able to benchmark themselves against them," he says. "Through CLARITY, we've learned that the best teams in the world, when given raw sequence data, agree fairly closely on results, the meaning of the results and how to deliver them. The best teams were able to elucidate a precise cause for previously unexplained genetic disorders."

"The contestants have demonstrated that genomics, bioinformatics and biotechnology can now have routine relevance in clinical care," says Isaac Kohane, MD, Ph.D., chair of the Children's Hospital Informatics Program and CLARITY's third co-organizer. "They also demonstrate the range of disciplines required to safely and rapidly interpret the millions of variants that are present in all of our genomes."

The CLARITY team plans a second challenge around interpretation of cancer genomes, and will lead a Clinical Bioinformatics Summit in Boston next spring to hammer out the details.

"It is essential that families are cared for by practitioners who are trained in the use of genomic analysis," notes Margulies. "Training of care providers will be the next challenge."

For further background, visit www.childrenshospital.org/CLARITY, and see:

Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 395-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Boston Children's also is a teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Boston Children's, visit: http://vectorblog.org/.

CONTACT:
Keri Stedman
Boston Children's Hospital
617-919-3110 
(cell 774-244-6490 at ASHG meeting) 
[email protected]

Cathy Yarbrough  
ASHG
858-243-1814
[email protected]

SOURCE Boston Children's Hospital

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
In a recent research, analyst firm IDC found that the average cost of a critical application failure is $500,000 to $1 million per hour and the average total cost of unplanned application downtime is $1.25 billion to $2.5 billion per year for Fortune 1000 companies. In addition to the findings on the cost of the downtime, the research also highlighted best practices for development, testing, application support, infrastructure, and operations teams.
"We specialize in testing. DevOps is all about continuous delivery and accelerating the delivery pipeline and there is no continuous delivery without testing," noted Marc Hornbeek, Sr. Solutions Architect at Spirent Communications, in this SYS-CON.tv interview at @DevOpsSummit, held June 9-11, 2015, at the Javits Center in New York City.
How do you securely enable access to your applications in AWS without exposing any attack surfaces? The answer is usually very complicated because application environments morph over time in response to growing requirements from your employee base, your partners and your customers. In his session at @DevOpsSummit, Haseeb Budhani, CEO and Co-founder of Soha, shared five common approaches that DevOps teams follow to secure access to applications deployed in AWS, Azure, etc., and the friction an...
"Alert Logic is a managed security service provider that basically deploys technologies, but we support those technologies with the people and process behind it," stated Stephen Coty, Chief Security Evangelist at Alert Logic, in this SYS-CON.tv interview at 16th Cloud Expo, held June 9-11, 2015, at the Javits Center in New York City.
Digital Transformation is the ultimate goal of cloud computing and related initiatives. The phrase is certainly not a precise one, and as subject to hand-waving and distortion as any high-falutin' terminology in the world of information technology. Yet it is an excellent choice of words to describe what enterprise IT—and by extension, organizations in general—should be working to achieve. Digital Transformation means: handling all the data types being found and created in the organizat...
The essence of cloud computing is that all consumable IT resources are delivered as services. In his session at 15th Cloud Expo, Yung Chou, Technology Evangelist at Microsoft, demonstrated the concepts and implementations of two important cloud computing deliveries: Infrastructure as a Service (IaaS) and Platform as a Service (PaaS). He discussed from business and technical viewpoints what exactly they are, why we care, how they are different and in what ways, and the strategies for IT to tran...
The Internet of Everything (IoE) brings together people, process, data and things to make networked connections more relevant and valuable than ever before – transforming information into knowledge and knowledge into wisdom. IoE creates new capabilities, richer experiences, and unprecedented opportunities to improve business and government operations, decision making and mission support capabilities.
The Software Defined Data Center (SDDC), which enables organizations to seamlessly run in a hybrid cloud model (public + private cloud), is here to stay. IDC estimates that the software-defined networking market will be valued at $3.7 billion by 2016. Security is a key component and benefit of the SDDC, and offers an opportunity to build security 'from the ground up' and weave it into the environment from day one. In his session at 16th Cloud Expo, Reuven Harrison, CTO and Co-Founder of Tufin,...
The Internet of Things is not only adding billions of sensors and billions of terabytes to the Internet. It is also forcing a fundamental change in the way we envision Information Technology. For the first time, more data is being created by devices at the edge of the Internet rather than from centralized systems. What does this mean for today's IT professional? In this Power Panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists addressed this very serious issue of pro...
Container technology is sending shock waves through the world of cloud computing. Heralded as the 'next big thing,' containers provide software owners a consistent way to package their software and dependencies while infrastructure operators benefit from a standard way to deploy and run them. Containers present new challenges for tracking usage due to their dynamic nature. They can also be deployed to bare metal, virtual machines and various cloud platforms. How do software owners track the usag...
With SaaS use rampant across organizations, how can IT departments track company data and maintain security? More and more departments are commissioning their own solutions and bypassing IT. A cloud environment is amorphous and powerful, allowing you to set up solutions for all of your user needs: document sharing and collaboration, mobile access, e-mail, even industry-specific applications. In his session at 16th Cloud Expo, Shawn Mills, President and a founder of Green House Data, discussed h...
Discussions about cloud computing are evolving into discussions about enterprise IT in general. As enterprises increasingly migrate toward their own unique clouds, new issues such as the use of containers and microservices emerge to keep things interesting. In this Power Panel at 16th Cloud Expo, moderated by Conference Chair Roger Strukhoff, panelists addressed the state of cloud computing today, and what enterprise IT professionals need to know about how the latest topics and trends affect t...
"Our biggest growth area has been the security services, the managed services - the things that differentiate us in the market that there is no client that's too small and there's no client that's too big," explained Paul Mazzucco, Chief Security Officer at TierPoint, in this SYS-CON.tv interview at 16th Cloud Expo, held June 9-11, 2015, at the Javits Center in New York City.
SYS-CON Events announced today that HPM Networks will exhibit at the 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. For 20 years, HPM Networks has been integrating technology solutions that solve complex business challenges. HPM Networks has designed solutions for both SMB and enterprise customers throughout the San Francisco Bay Area.
Containers are changing the security landscape for software development and deployment. As with any security solutions, security approaches that work for developers, operations personnel and security professionals is a requirement. In his session at DevOps Summit, Kevin Gilpin, CTO and Co-Founder of Conjur, will discuss various security considerations for container-based infrastructure and related DevOps workflows.