Fig. 2: Sex- and brain region-specific miRNA variation in the mouse brain.
a Heatmaps of the 50 top miRNA from brain regions determined by the coefficient of variation calculated using the medians of the expression values of each brain region. Shown are the absolute standardized expression values (z-scores) for the younger male (left) and younger female (right) samples. Black borders indicate the binarization (|z-score|> 0.5) on which a clustering into four clusters using a hierarchical clustering was applied. We consider a miRNA in a brain region different from the average brain if it surpasses the aforementioned threshold. If it only exceeds the threshold for one brain region, we call it brain region-specific. Lines connecting the two heatmaps are highlighting the occurrence of common features (light green). If features are differing from the average brain for only one but the same brain region in both sexes, they are highlighted in pink and in dark green if they differ from the average brain in the same set of multiple brain regions. For visualization purposes, we removed features entirely below the selected threshold. b Venn diagram linking the features which are differing from the average brain per brain region between the male and female heatmap. c PVCA showing the observed variance for each brain region individually over all sex-matched samples (3, 12, 15, 18, 21 months) for age and sex. The point size indicates the variance when observing age and sex in combination. Colors refer to the brain regions (Fig. 1a). Thresholds at 12% for both axes are marked with grey dashed lines. d Volcano plot for the sex-specific comparison of mot. cortex, choroid plexus, thalamus and olfactory bulb. Colored dots indicate significantly down (green) and significantly upregulated (yellow) miRNAs (fold change \(\ge\) 1.5 or \(\le\) 1/1.5, adjusted p-value < 0.05, two-sided Welch’s \(t\)-test, Benjamini-Hochberg procedure). e The gene set enrichment analysis (GSEA) results obtained from MIEAA60 for mot. cortex, choroid plexus, thalamus showing the top 10 depleted (green) and enriched (yellow) pathways (cf. Methods).
