Bioinformatics support to the clinician: Unlock insights from RNA-seq data

Situation

Kristl Claeys, MD, PhD, is a neurologist specialized in neuromuscular disorders working at the University Hospitals Leuven, Belgium. In Leuven, she is affiliated with the largest Neuromuscular Reference Centre in Belgium. Since 2016, Prof. dr. Kristl Claeys is heading the Laboratory for Muscle Diseases and Neuropathies at the Department of Neurosciences at KU Leuven.

Kristl Claeys is an author of 200+ publications in international peer-reviewed journals and wrote several book chapters on diverse topics in the field of neuromuscular disorders. Her research topics are clinical research and genetics in neuromuscular disorders, with a focus on hereditary muscle diseases. Moreover, she also has a special interest in translational medicine in neuromuscular disorders specifically in unraveling the clinical, molecular and genomic characteristics of Limb Girdle disease, a diverse group of muscular dystrophies.

Challenge

To investigate the molecular characteristics of limb-girdle muscular dystrophy type 12, the Claeys lab had generated a large bulk RNA-seq dataset of multiple muscle biopsies in healthy and affected patients. The Claeys lab did not have in-house expertise to transform the RNA-seq data into insights that supported a compelling narrative, and the core facility only performed basic analyses. Consequently. the data remained unanalyzed for two years

Solution 

Unicle inventoried the challenge and designed a strategy that leveraged the UniApp and Unicle consultancy. Specifically, Unicle bioinformatics experts analyzed the bulk RNA-seq data on the UniApp platform. All these analyses were done in close collaboration with the team of Dr. Claeys. In total, over the course of three months, we analyzed over 90 samples, resulting in more than 30 main figure panels and several tables. We performed quality controls, differential analysis, pathway analysis, deconvolution analysis and heatmap analysis with clustering among others.

Hereafter, we identified transcriptomics differences in healthy and disease muscles, between muscle types and provided first molecular insight into possible disease mechanisms. All results and analyses were delivered as an interpreted report, including publication-ready figures and detailed materials and methods sections.

Result

The first result of the collaboration was to unlock the valuable RNA-seq data processed two years ago, within two months after initializing the collaboration. In the remaining 12 months thereafter, the Claeys team published the results of their RNA-seq effort in Cells (IF6.0). The Claeys lab also envisioned future projects leveraging single cell and spatial sequencing techniques to further characterize muscle biopsies from limb girdle patients, Unicle helped to write the bioinformatics work packages of grants to get these projects funded. Read also our client success story on one of Prof. Claeys follow-up projects, where we analyzed data from a retrospectively collected clinical cohort.

• Publication in Cells
• Follow-up project client success story (Brain paper)
• Unicle Bioinformatics support

“Great and fruitful collaboration with top specialists from diverse complementary disciplines“

Prof. dr. Kristl Claeys
Department of Neuro sciences, Laboratory for Muscle Diseases and Neuropathies, KU Leuven
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