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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer’s disease

Fig. 3

Replication co-expression analysis of microglial transcriptomic datasets across neuroinflammatory and neurodegenerative disease models. a Cluster dendrogram summarizing results of validation WGCNA performed using 64 existing Nanostring purified microglial transcriptomic datasets (369 genes in common across all conditions). Datasets included aging WT and APP/PS1 models (age range 2–17 mo, n = 24), WT and SOD1-G93A transgenic mice (n = 13), control and various stages of EAE in mice (n = 21) and WT and intra-cerebral LPS-treated WT mice (n = 6). Expression data were first batch-corrected followed by WGCNA to identify modules of highly co-expressed genes. b Module over-representation analysis (ORA) of derivation (43 microglial arrays, y-axis) and validation WGCNA (64 microglial Nanostring transcriptomic datasets, x-axis) studies. Module overlap was assessed by Fisher-exact test and the negative log10 transformed false discovery rate (FDR) for overlap is indicated by color intensity. Validation modules are numbered (M1–19) while derivation modules are indicated by the original color scheme. c Module eigengene expression and trajectories of change in module expression across various traits in the Nanostring co-expression dataset. Validation modules highlighted here were chosen based on strength of overlap from the over-representation analysis. M6 and M7 are representative of the Blue homeostatic derivation module. M4 is representative of the Yellow anti-inflammatory derivation module while M3 is representative of the Magenta pro-inflammatory derivation module. M1 is representative of LPS-induced Midnightblue derivation module while M19 is representative of the IL4-upregulated Cyan derivation module

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