WGCNA
(A) WGCNA identified 26 modules marked by specific colors across the neuronal dataset. Height indicates the dissimilarity between genes, which was based on topological overlap.
(B) Module eigengenes for each module were compared between two groups of cells: i.e., SOD1 ipMN versus control (CTR) ipMN or control ipMN versus ipIN. For a comparison of group A versus group B, red (positive correlation) indicates that the module eigengenes were higher in group A compared with group B, while blue (negative correlation) indicates the reverse. Correlations with an adjusted p value <0.01 were considered significant (outlined in yellow).
(C) GO enrichment analysis of modules significantly correlated (positive or negative) with SOD1 ALS ipMNs. p values shown were adjusted using the Benjamini-Hochberg procedure. Module lightcyan1 did not yield any significant GO terms and is not shown. The red dashed line indicates a p value threshold of 0.05.
(D) Enrichment of WGCNA modules in genes upregulated in neural progenitors compared with neurons. D0 indicates NMPs. D1 to D8 indicate intermediate time points as the NMP differentiated into MN, while D15, D21, and D35 indicate genes enriched in MNs. The red rectangle highlights modules activated in SOD1 ipMNs, while the green rectangle highlights the single module downregulated in SOD1 ipMNs. Enrichments were estimated using a one-way GSEA. Heatmap shows log-transformed p values.
(E) GSEA performed was similar to (D), where genes upregulated (Up) or downregulated (Down) in SOD1 ipMNs were used as gene sets for the GSEA.
(F) Enrichment of WGCNA modules in publicly available ALS datasets (Table 1). The x axis shows the modules. The red rectangle highlights modules activated in SOD1 ipMNs, while the green rectangle highlights the single module downregulated in SOD1 ipMNs. Log-transformed p values were assigned the same sign as the GSEA enrichment scores and plotted as a heatmap. Red indicates positive enrichment, while green indicates negative enrichment of a module in the queried dataset.
See also Figure S3.