CCOS is pleased to announce a new series of hub highlights featuring the innovative clinical and translational science coming out of the CTSA Program. We will feature groundbreaking work from each hub in the CTSA program over the coming months, selected at random. Next up on the benchtop for analysis is the University of Utah’s Clinical and Translational Science Institute (CTSI).
The University of Utah's CTSI is untangling mysteries in genomic medicine with their Specialized Innovation Program. This program addresses significant challenges in the field of genomic sequencing, specifically the detection of genetic mutations in hard-to-sequence regions of the genome. The CTSI’s solution is the development of the Tandem Repeat Genotyping Tool (TRGT), a computational method that can profile genetic variations across an entire genome. This advanced bioinformatics tool has been seamlessly integrated into clinical workflows, providing direct and immediate benefits to patients.
The human genome still holds a wealth of undiscovered information that can be utilized for the detection and treatment of genetic diseases. It’s normal for genomes to vary between people, but a change in a gene can result in a variety of consequences for a person’s health. Much of our genetic diversity is due to tandem repeats, repeating sequences in a region of the genome. Occasionally these tandem repeats overextend, leading to diseases like Huntington’s disease or Fragile X syndrome. The number of repeats can also vary between individual cells in a body, a phenomenon known as genetic mosaicism, making it even more difficult to link a tandem repeat to a disease. Despite the link between tandem repeat length and disease progression, tandem repeats have been understudied.
There are methods for profiling different features of a repeat sequence, but they decrease in accuracy the longer a repeat sequence is, or they can only work on parts of the genome that aren’t coiled too tightly. Many known tandem repeats only become harmful when the sequence reaches hundreds of base pairs in length, too long for current methods to detect.
A team from the Utah CTSI collaborated with Pacific Biosciences to publish a new method of visualizing tandem repeats in Nature Biotechnology. The TRGT can profile tandem repeats across an entire genome sequence. This gives researchers the power to detect tandem repeats associated with complex traits, like those that may skip a generation.
In addition to TRGT, the researchers also developed two more tools: TRGTdb, and Tandem Repeat Visualization. TRGTdb is a database of tandem repeats that allows researchers to compare a single genome to a population. This tool can identify regions in that sample that are significantly longer than those in the general population, which could aid in diagnosing a disease. The Tandem Repeat Visualization tool plots out repeat sequences from a genome, allowing researchers to visualize changes in repeat sequences between samples. Together, these tools can characterize known harmful tandem repeats, providing a quick way to diagnose certain diseases.
The Specialized Innovation Program doesn’t end in the lab— it also seeks to implement new genomic tools like TRGT into clinical care. During a recent interview with CCOS, Dr. Rachel Hess, Co-Director of the Utah CTSI, emphasized the critical role of community engagement and implementation science in accelerating clinical and translational benefits. The program is working to develop strategies to support the adoption of rapid genomic diagnostic tools, like TRGT, in neonatal intensive care units. This underscores Dr. Hess’s commitment to moving discoveries into the community, ensuring that benefits are not confined to academic medical centers but are also accessible in the hub’s rural healthcare facilities.
The Utah CTSI has also embraced cross-hub collaboration to enhance their programs. Dr. Hess highlighted the CTSI's adoption of a voucher program, inspired by other hubs, to provide small-scale funding support for researchers. This program addresses the need for quick financial assistance to overcome specific challenges in clinical and translational science projects. For example, obtaining funding for survey design typically takes months, slowing down the research process. This initiative allows decisions to be made within two weeks, maintaining project momentum and circumventing lengthy administrative processes. Although these funds are awarded from other university allocations and not the CTSA program directly, this initiative exemplifies effective cross-hub collaboration and innovation, demonstrating our hubs are aligning with the strategic goal NCATS set to reducing barriers in translational science.
The University of Utah CTSI’s Specialized Innovation Program exemplifies the transformative potential of interdisciplinary collaboration and innovative solutions in the field of translational genomics. By addressing critical challenges in genomic sequencing and integrating advanced tools like the Tandem Repeat Genotyping Tool into clinical workflows, this CTSA hub is paving the way for rapid and accurate genomic diagnostics. The commitment to community engagement and the strategic adoption of cross-hub initiatives, such as the voucher program, further highlight the program's dedication to reducing barriers and accelerating the translation of scientific discoveries into tangible health benefits for all.
