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
The essence of data analysis involves setting up data pipelines that consist of several operations that are chained together – starting from data collection, data quality checks, data integration, data analysis and data visualization (including the setting up of interaction paths in that visualization). In our opinion, the challenges stem from the technology diversity at each stage of the data pipeline as well as the lack of process around the analysis.
Many banks and financial institutions are experimenting with containers in development environments, but when will they move into production? Containers are seen as the key to achieving the ultimate in information technology flexibility and agility. Containers work on both public and private clouds, and make it easy to build and deploy applications. The challenge for regulated industries is the cost and complexity of container security compliance. VM security compliance is already challenging, ...
As cloud and storage projections continue to rise, the number of organizations moving to the cloud is escalating and it is clear cloud storage is here to stay. However, is it secure? Data is the lifeblood for government entities, countries, cloud service providers and enterprises alike and losing or exposing that data can have disastrous results. There are new concepts for data storage on the horizon that will deliver secure solutions for storing and moving sensitive data around the world. ...
In his session at 18th Cloud Expo, Bruce Swann, Senior Product Marketing Manager at Adobe, will discuss how the Adobe Marketing Cloud can help marketers embrace opportunities for personalized, relevant and real-time customer engagement across offline (direct mail, point of sale, call center) and digital (email, website, SMS, mobile apps, social networks, connected objects). Bruce Swann has more than 15 years of experience working with digital marketing disciplines like web analytics, social med...
Designing IoT applications is complex, but deploying them in a scalable fashion is even more complex. A scalable, API first IaaS cloud is a good start, but in order to understand the various components specific to deploying IoT applications, one needs to understand the architecture of these applications and figure out how to scale these components independently. In his session at @ThingsExpo, Nara Rajagopalan is CEO of Accelerite, will discuss the fundamental architecture of IoT applications, ...
As machines are increasingly connected to the internet, it’s becoming easier to discover the numerous ways Industrial IoT (IIoT) is helping to shape the business world. This is exactly why we have decided to take a closer look at this pervasive movement and to examine the desire to connect more things! Now if you need a refresher on IIoT and how it is changing the world, take a moment and listen to Greg Gorbach with ARC Advisory Group. Gorbach believes, "IIoT will significantly change the worl...
Enterprise networks are complex. Moreover, they were designed and deployed to meet a specific set of business requirements at a specific point in time. But, the adoption of cloud services, new business applications and intensifying security policies, among other factors, require IT organizations to continuously deploy configuration changes. Therefore, enterprises are looking for better ways to automate the management of their networks while still leveraging existing capabilities, optimizing perf...
What a difference a year makes. Organizations aren’t just talking about IoT possibilities, it is now baked into their core business strategy. With IoT, billions of devices generating data from different companies on different networks around the globe need to interact. From efficiency to better customer insights to completely new business models, IoT will turn traditional business models upside down. In the new customer-centric age, the key to success is delivering critical services and apps wit...
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York and Silicon Valley. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 17th Cloud Expo and will feature technical sessions from a rock star conference faculty ...
The 19th International Cloud Expo has announced that its Call for Papers is open. Cloud Expo, to be held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, brings together Cloud Computing, Big Data, Internet of Things, DevOps, Containers, Microservices and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding business opportunity. Submit y...
Cloud computing changed data analytics for good. It enabled companies to drastically decrease resources and architecture previously assigned with business intelligence departments. It also enabled laymen to run advanced business analytics. Cloud was also the architecture of choice for storing and processing big data. Data piling is a continuous process, which is going to explode with emerging Internet of Things concept. Answer to this issue developers found in new concept called fog computing. ...
There are several IoTs: the Industrial Internet, Consumer Wearables, Wearables and Healthcare, Supply Chains, and the movement toward Smart Grids, Cities, Regions, and Nations. There are competing communications standards every step of the way, a bewildering array of sensors and devices, and an entire world of competing data analytics platforms. To some this appears to be chaos. In this power panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists will discuss the vast to...
Internet of @ThingsExpo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with the 19th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world and ThingsExpo New York Call for Papers is now open.
SYS-CON Events announced today that Enzu, a leading provider of cloud hosting solutions, will exhibit at SYS-CON's 18th International Cloud Expo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. Enzu’s mission is to be the leading provider of enterprise cloud solutions worldwide. Enzu enables online businesses to use its IT infrastructure to their competitive advantage. By offering a suite of proven hosting and management services, Enzu wants companies to foc...
SYS-CON Events announced today the How to Create Angular 2 Clients for the Cloud Workshop, being held June 7, 2016, in conjunction with 18th Cloud Expo | @ThingsExpo, at the Javits Center in New York, NY. Angular 2 is a complete re-write of the popular framework AngularJS. Programming in Angular 2 is greatly simplified. Now it’s a component-based well-performing framework. The immersive one-day workshop led by Yakov Fain, a Java Champion and a co-founder of the IT consultancy Farata Systems and...