Convincing bioinformatics from clinical cohort 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.

Prof. 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

After having successfully collaborated on a bulk RNA-seq analysis, the Claeys lab asked our support to develop the analysis for a retrospectively collected clinical cohort. Specifically, the Claeys lab headed a large European consortium that created a detailed dataset on the genotypes and clinical characteristics in limb-girdle patients. This data had to be analyzed to identify genotypic and phenotypic predictors of disease progression.

Solution 

Unicle inventoried the challenge and designed a strategy where statistical, medical and genetics consultants of Unicle performed detailed statistical analysis in close collaboration with the team of Dr. Claeys. In total, we analyzed 234 patients from 212 different families, contributed by 15 centers from 11 European countries. We developed our analysis in stratified groups of patients. Because stratified analysis inevitably leads to a drop in statistical power, we devised multivariate survival analysis (Cox regression models) strategies with potential confounders as a covariate. Together, we produced all twelve figure panels of the paper.

Result

Within two months after receiving the data, de bioinformatic analysis were delivered in publication-ready formats with detailed description of the methodologies and algorithms used. Hereafter, the Claeys team turned the analysis into a convincing scientific narrative. The Claeys team published the results of our analysis in the top clinical neurology journal Brain (IF14.5).

“Thank you for your support and expert advice. We are looking forward to future opportunities for collaboration“

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