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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations

Fig. 1

Proteomics and network analysis of Grn+/+ and Grn−/− mouse brain. a Schematic overview of experimental design. Quantitative proteomic analysis of the cerebral cortex of 3-month-old (n = 4 Grn+/+, n = 4 Grn−/−) and 19-month-old (n = 4 Grn+/+, n = 4 Grn−/−) mice was performed using Tandem Mass Tag (TMT) isobaric labeling and synchronous precursor selection-based MS3 (SPS-MS3) mass spectrometry. b, c Volcano plots illustrating differentially expressed proteins in 3- and 19-month-old mouse brains. Relative protein abundance (log2 Grn−/−/ Grn+/+) plotted against significance level (− log10 P-value), showing significantly (p < 0.05) decreased (Grn−/−/ Grn+/+ ratio < log2(− 1.25); green) and increased (Grn−/−/ Grn+/+ ratio > log2(1.25); red) proteins in Grn−/− mice. d WGCNA cluster dendrogram generated by hierarchical clustering of highly co-expressed genes followed by identifying 26 distinct modules coded by different colors. e Two-color heatmap is showing the relationship between modules and the bicor correlation of genotype. Significance levels are ****p < 0.0001, ***p < 0.001, **p < 0.01 and *p < 0.05. f Significance of cell type overlap is shown by one-color heatmap with P values. Relevance between each module and cell type was assessed by protein module overlap with known mouse microglia, astrocyte, neuron and oligodendrocyte markers. Significance levels are ****p < 0.0001, ***p < 0.001, **p < 0.01 and *p < 0.05

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