Identifying Potential Biomarkers for Duchenne Muscular Dystrophy in Urinary Metabolomics Data.

Duchenne Muscular Dystrophy (DMD) is a serious muscular disease that ultimately causes premature death. To research DMD, biomarkers are used to track its progression or evaluate potential treatments. Obtaining biomarkers from skeletal muscle however, is a very invasive process and does not provide information on the overall status of the body. So, easy accessible alternatives that can also give overall information, such as urine, are researched. This thesis contributes to that by aiming to identify new, potential biomarkers in urine from DMD patients and mice. With urine data from mice available, we used linear mixed models (LMMs) to model the expression linearly for each metabolite. With these modelled trajectories, we were able to test some hypotheses to compare different mouse groups. This resulted in five interesting metabolites showing significant difference in expression levels between wild type and \textit{mdx} mice. From these five metabolites, three metabolites show a clear...Show moreDuchenne Muscular Dystrophy (DMD) is a serious muscular disease that ultimately causes premature death. To research DMD, biomarkers are used to track its progression or evaluate potential treatments. Obtaining biomarkers from skeletal muscle however, is a very invasive process and does not provide information on the overall status of the body. So, easy accessible alternatives that can also give overall information, such as urine, are researched. This thesis contributes to that by aiming to identify new, potential biomarkers in urine from DMD patients and mice. With urine data from mice available, we used linear mixed models (LMMs) to model the expression linearly for each metabolite. With these modelled trajectories, we were able to test some hypotheses to compare different mouse groups. This resulted in five interesting metabolites showing significant difference in expression levels between wild type and \textit{mdx} mice. From these five metabolites, three metabolites show a clear difference between healthy and DMD mice; two show this in their predicted intercept and one in its slope. This indicates a potential in using urine for Duchenne biomarkers, despite the available data having its limitations. The available human data was more difficult to analyse, because of the missing values it has and the asymmetric distribution of the samples. This means that we were not able thoroughly analyse this data. However, we did do a descriptive analysis from which a conclusion could be drawn. We found the metabolite creatine to be a promising biomarker for DMD in human urine, as it shows a clear difference between healthy and DMD patients. Overall, while not being able to couple the datasets together due to the missing labels in the mouse data, we did conclude that there is potential in urine for obtaining biomarkers for DMD.Show less

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Identifying Potential Biomarkers for Duchenne Muscular Dystrophy in Urinary Metabolomics Data.