Children’s Mercy Research Institute Releases Genomic Data from First-of-its-Kind Repository Accelerating Answers for Kids with Rare Disease
The Children’s Mercy Research Institute (CMRI) in Kansas City, Mo., announced it has released more than 2,300 pediatric rare disease genomes through its Genomic Answers for Kids (GA4K) program making it one of the largest, pediatric rare disease whole genomic datasets ever publicly shared. A subset of the data has been recently submitted for publication and is available as a preprint.
GA4K is a first-of-its-kind approach to analyzing and sharing genomic data, with a goal to lead the world in diagnosis rates for pediatric rare disease. To-date, more than 3,160 patients with rare disease have enrolled in the GA4K program, which has resulted in more than 16,000 new genomic analyses and more than 586 genetic diagnoses. In addition, the program has advanced research genomic analyses for children of 350 families with more common childhood disease: cerebral palsy and Down's Syndrome.
“The unfortunate reality is that rare diseases often go undiagnosed for far too long – children typically wait four to six years before being diagnosed,” said Tom Curran, PhD, FRS, Senior Vice President, Executive Director and Chief Scientific Officer, Children's Mercy Research Institute. “By providing an open and collaborative environment, such as GA4K, we are helping move kids to the forefront of research discoveries much sooner.”
The unique aspect of GA4K is that the full pediatric data repository will now be shared in a real-time web interface through a comprehensive process, which gives researchers and clinicians low barrier access to processed data with disease prioritized genetic changes accounting for more than 10,000 variants per patient. GA4K also periodically deposits full raw sequence data of patients and family members, which is accessible through the National Institutes of Health dbGAP .
“Giving access to our data allows researchers to link their own genetic findings so they can accept or reject hypotheses on their gene discoveries,” said Tomi Pastinen, MD, PhD., Director, Genomic Medicine Center, Children’s Mercy Kansas City. “Data sharing is the only way we’ll make headway in the quicker delivery of results that are non-diagnostic today.”
GA4K would not be possible without the generosity of the Kansas City community. The program has received approximately $18 million in funding from 200 donors.
“Because of these donors, researchers around the world will be able to understand and diagnose the most challenging pediatric diseases – truly changing the lives of our patients and their families,” said Dr. Curran.
Learn more about Genomic Answers for Kids at Children's Mercy Kansas City.
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About Preprint Data Publication
In addition to the data release, Dr. Pastinen and colleagues describe their approach in the manuscript “Genomic answers for children: Dynamic Analyses of >1000 pediatric rare disease genomes,” available as preprint which takes a comprehensive look at diagnostics and candidate variant genome analyses in pediatric rare disease patients through the GA4K program.
A total of 1,083 patients with suspected genetic disorders were part of the study. All individuals received short-read exome sequencing (ES) and were followed up by genome sequencing (GS), long-read genome sequencing (lrGS) and machine-learning variant prioritization.
The study revealed that 30% of patients received a diagnosis after the first gene test. Importantly, if earlier testing had failed, an additional 12% of patients were given a conclusive diagnosis – ending diagnostic odysseys that typically last several years.
Furthermore, the team prioritized candidate variants for 48% of patients beyond the confirmed clinical diagnoses and showed that some variants are dependent on the sequencing technology used. The results indicate that better systems that accelerate prioritized gene validation and newer sequencing tools, such as long-read genome sequencing (lrGS), are needed.
“Crowd-sourcing data to advance the course of unsolved rare disease is the ethical and right thing to do,“ said Dr. Pastinen. “We are advocating a unique approach and we hope others will actively join us in expanded data sharing.” In parallel with sharing patient and prioritized variant data, the team is making their lrGS “reference” data openly accessible allowing others to use lrGS in rare disease.