Fig. 8: MS1262 treatment of AD mice reversed AD patient proteome or phosphoproteome.
A Heatmap depicting AD/G9a co-regulated proteins/phosphoproteins showing dysregulation in 5x-FAD/APP-NLGF mice, compared to age-matched controls, whose expression/phosphorylation pattern is reversed following MS1262 treatment. Right annotation columns depict log2(fold-change) for indicated comparisons (AD/WT & AD-tr/AD). B, C Heatmaps summarizing results of GO/pathway enrichment (B) and disease & function (C) analyses for proteins and phospho-proteins belonging to the two clusters identified in (A). P-values were calculated using cumulative hypergeometric distribution followed by Benjamini-Hochberg correction to account for multiple testing. All genes in the genome were used as enrichment background. D Volcano plot illustrating the relationship between expression levels of various proteins and the Aβ peptides (residues 6–28) in the brain of AD patients (n = 488)10. The plot shows the biweight mid-correlation (bicor) coefficient and the corresponding BH adjusted p-value for each protein. Cluster 1 (blue) and cluster 2 (red) proteins from (A) are highlighted with point shape denoting proteins (circle) and phospho-proteins (triangle). Names of select AD markers are shown. E Network illustrating the relationship between AD/G9a-coregulated proteins/phosphoproteins identified in (A) and various AD-patient correlated modules (‘M’) that are dysregulated in the brains of AD patients10. Modules showing dysregulation at protein level only, without concomitant change at the transcriptional level in AD patients, are highlighted using cyan outlines (see also Figure. S10 and Data S1D, F–H).
