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Rare diseases affect a small percentage of the population, but collectively, they impact millions. The University of Washington Genetic Analysis Center (GAC) plays a key role in efforts aimed at discovering the cause of currently unexplained rare genetic diseases, knowledge that could improve genetic testing, shorten time to diagnosis, and expand treatment options.

The GAC, part of the UW Department of Biostatistics, serves as the Data Coordinating Center (DCC) for the Genomics Research to Elucidate the Genetics of Rare (GREGoR) Consortium. Funded by the National Human Genome Research Institute (NHGRI), GREGoR includes 300 investigators from five research centers around the country, including one at the UW Center for Rare Disease Research (UW-CRDR). GREGoR has made significant advances over the years, as outlined in a recent Nature Perspective, and worked to lessen the burden on families affected by rare disease.

The DCC’s role within GREGoR is to connect doctors, clinicians, genetic counselors and other researchers with each other and with patients who have undiagnosed and rare genetic diseases. It also tackles the incredibly complex challenges involved in helping people organize and share data from different sources so that it can be analyzed collectively.

“Many technologies used by GREGoR scientists are so new that no data standards or agreements exist about how to organize and describe the data produced by their experiments,” said Ben Heavner, a GAC senior research scientist.

The DCC’s most significant innovation has been leading the development of the GREGoR Data Model, which aggregates information generated by these innovative technologies and enables new approaches to data validation, collaboration, and release.

Each group that generates data — such as long-read sequencing, RNA-sequencing, or other measurements — tends to organize and report data in a way that supports its specific research. This makes it difficult to combine data generated from all groups into one dataset for analysis.

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DCC scientists worked with the GREGoR Data Standards & Analysis Working Group to define a data model that enables a single, cohesive, and extendable dataset of more than 10,500 participants across 4,366 families that can be shared within the GREGoR Consortium and released for controlled-access use by researchers around the world.

“Putting this data together helps doctors and researchers discover new ways to diagnose the genetic and molecular underpinnings of rare diseases. The cohesive dataset that the DCC is assembling will provide a lasting legacy that will be available to researchers investigating different genome sequencing and other molecular data, even beyond the rare disease context,” said UW Assistant Professor of Biostatistics Guanghao Qi, who serves as a faculty advisor for the DCC.

Groups outside of GREGoR are working to adopt the GREGoR data model so that their data can be combined with the consortium dataset for more advanced analysis with greater statistical power.

“Consortium members are driven by the desire to help patients, and are eager to encourage broader expert analysis of their data. Each research center is a recognized leader in the area of rare disease research, but they’re all excited for the additional insights that have been achieved through collaborative work,” said Ali Shojaie, interim chair and professor with the UW Department of Biostatistics who serves as DCC co-principal investigator.

The DCC’s contributions to Consortium achievements are not limited to the data model.

“We are proud to be involved in the day-to-day work of the GREGoR Consortium, helping reach important milestones such as discovering the genetic causes of participants’ rare diseases and sharing these advances at scientific meetings such as the American Society of Human Genetics annual meetings,” said Marsha Wheeler, a GAC research scientist.

“It’s exciting to be part of a collaborative science effort, particularly one as successful as the GREGoR Consortium,” said Wheeler.