CORRELATING RATIOS OF AMINES IN PLASMA AND CEREBROSPINAL FLUID 55 3 transformed the difference in z-value back with the inverse Fisher transformation to get a measure of the gain in the ratio correlation coefficient with respect to single metabolites. Multiple test correction was performed by using Benjamini Hochberg’s procedure. A p value < .05 was considered significant after false discovery rate (FDR) correction. Coefficients of determination (R2) and R2 ratio gains (R2 gain) for all metabolite ratios were plotted in a heatmap using R software (version 3.6.3 with package gplots and heatmap.2 function). Results Amines in blood plasma and CSF of healthy controls Concentrations of amines In blood plasma, 40 amines were reliably measured in healthy controls. In CSF, o-phosphoethanolamine showed abnormally high concentrations (> 3 SDs above median) in multiple samples from one batch and was, therefore, excluded leaving 39 amines for further analysis. No other metabolite in plasma nor CSF showed such batch effect. At the individual level, PCA identified one clear outlier in both plasma and CSF that, therefore, was excluded, leaving amine profiles of 95 healthy controls for further analysis (Table 1). Later, it turned out that the excluded participant suffered from cardiac disease. Blood plasma concentrations were higher than CSF concentrations for most amines in healthy controls (Table 2). Only concentrations of ethanolamine and putrescine were higher in CSF than plasma. L-Glutamine was the most abundant amine in CSF (median: 591 mM, interquartile range: 539-638 mM), with similar concentrations in blood (median: 665 mM, interquartile range: 600-715 mM). Single-metabolite correlations between plasma and CSF Both correlation coefficients (r), and coefficients of determination (R2) were calculated to show the percentage of variation explained by a linear model. Most amines showed a low single/direct correlation between plasma and CSF concentrations (Table 3). Four of 39 amines (10.3%) had a correlation coefficient ≥ .70, namely, homocitrulline, S-methylcysteine, methionine sulfone, and L-alpha-aminobutyric acid (Table 3). Figure 1 shows the correlation plots of the log10-transformed uncorrected data of the four best correlating amines, the remaining plots can be found in the Supplementary Data (Figure S1). The four amines did not show
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