UDON Method Reveals Shared Gene Programs Across Inflammatory Diseases
Research By: Emely Verweyen, PhD | Grant Schulert, MD, PhD
Post Date: November 15, 2023 | Publish Date: Nov. 15, 2023
Rheumatology | Top Scientific Achievement
Research led by experts at Cincinnati Children’s has produced a novel method for detecting “gene programs” that may be shared across different rare inflammatory diseases, which may lead to new treatments for some conditions and improved tests to detect some diseases before classic symptoms emerge.
The findings emerge from a single-cell genetic analysis project that sought to dive deeper into the underlying mechanisms of immune-mediated disorders including systemic juvenile idiopathic arthritis (SJIA) and adult and pediatric lupus. The work was led by first author Emely Verweyen, PhD, and corresponding author Grant Schulert, MD, PhD, Division of Rheumatology.
To overcome existing analytical limitations, the team developed an investigational workflow they called “unsupervised discovery of novel disease programs” or UDON. Then they connected the gene programs to clinical and laboratory markers in a process they dubbed the “Statistical Association Test for ClinicAl PhenotYpes” or SATAY-UDON.
These methods revealed several “UDON clusters” that suggested distinct genomic signatures between subsets of patients with SJIA.
“Critically, we found that UDON clusters represent not just features of SJIA pathogenesis, but broadly conserved transcriptional programs present across inflammatory disease states,” Schulert says.
A number of UDON clusters at work in SJIA also were found when studying lupus cells, including shared gene programs found in some “healthy” patient samples. This suggests that some individuals may be exhibiting subclinical disease activity or a predisposition to autoimmune disease.
Cincinnati Children’s co-authors also included Sanjeev Dhakal, BS, Elizabeth (Joy) Baker, Kairavee Thakkar, BS, Kashish Chetal, BS, Daniel Schnell, PhD, and Nathan Salomonis, PhD; Scott Canna, MD, of the Children’s Hospital of Philadelphia also contributed.
Explore the 2024 Research Annual Report
| Original title: | Population-level single-cell genomics reveals conserved gene programs in systemic juvenile idiopathic arthritis |
| Published in: | Journal of Clinical Investigation |
| Publish date: | Nov. 15, 2023 |
Research By
Latest Posts
About this blog
The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
Subscribe to Our Newsletter