The Genomic Medicine Center at Children’s Mercy Hospital is working to sequence 100,000 genomes of children, siblings, and their parents with the hope of producing the largest data set of genetic information about children with rare diseases created to date.
The effort, known as the Genomic Answers for Kids program, is a seven-year, $80 million project at the Kansas City, Missouri-based hospital. The expectation is that studying the genetics of thousands of children will fuel progress in understanding rare diseases, identify undiscovered ones, and lead to faster diagnosis and new treatments.
“Families have struggled sometimes for decades, not getting a diagnosis,” said Dr. Tom Curran, senior vice president, chief scientific officer, and executive director of the Children’s Mercy Research Institute. “Providing that upfront as part of a research study, but under conditions that allows the data to be returned to the families, meant that we could provide answers for a very large number of families while advancing the field.”
The program is using a variety of technologies to capture pathogenic mutations that might otherwise go undetected. It’s using a method known as long sequencing, which Curran said provides a greater hit rate in rare genetic mutations. The program is also using single-cell genomics for complex disorders that have somatic mutations, and germline mutations.
The program, which launched before the COVID-19 pandemic, has enrolled 1,650 families with about 3,900 total participants to date. The project has already provided 160 new diagnoses, identifying 80 genes that may be contributing to disease in a research study of 720 families.
Curran called the data challenge involved in the project as “unbelievably enormous” and said we need new ways to deal with clinical informatics and genomic data.
“I don’t think there’s anyone who can tell you that they’re confident that they’re making the best use of data. This is an evolving situation,” he said. “We, along with many other institutions, are using AI approaches, but there is a long way to go. And this is where it’s very important to engage with the best and the brightest. One way to do that is to make your data available, so someone anywhere in the world can make a contribution to the interpretation of your data.”
The project has made a significant commitment to data sharing. Its data will be uploaded to the National Center for Biotechnology Information database of Genotypes and Phenotypes (dbGaP), which was developed to archive and distribute data and results from studies that have investigated the interaction of genotype and phenotype in humans. He said the research center is also developing a platform for real-time sharing that ultimately will be expanded for wide access.
“No single group has all the answers. And particularly with rare diseases, it’s very important to share information. You can learn from the experiences of others,” said Curran, who pointed to the case of one family with a rare mutation of unknown significance. When the program shared that information, it was able to identify an investigator who had identified a small number of families with the same disorder and same mutation.
“The more we share, the more we impact the data mix,” he said. “And our philosophy at Children’s Mercy in Kansas City is that although we’re very focused on our local demographic population, we actually believe we’re working for children everywhere in the world.”
RARE-X believes in that commitment to data sharing. It’s central to RARE-X’s entire reason for being. RARE-X understands that when it comes to rare disease data, the more that can be aggregated, the faster researchers will be able to gain new insights, and the faster we will be able to diagnose and treat patients.