Figure 6. Co‐expression analysis resolves C9orf72‐specific changes in ALS brain.

1. Volcano plot displays the protein abundance (log₂ fold change) against the t‐statistic (−log₁₀(P‐value)) for C9Pos (n = 8) against C9Neg (n = 11) ALS cases. Red and blue dots indicate significantly altered proteins that are increased and decreased, respectively, in C9orf72 carriers. Gray dots below the hashed line represent proteins that are not significantly changed (P > 0.05). Notably, there are no significant proteins that are twofold or more (±log₂ 1.0) increased or decreased in C9Pos cases compared to C9neg cases.
2. Stacked bar plot represents the analysis of differential expression (pairwise comparison between C9Pos and C9Neg ALS cases) and enrichment of differentially expressed proteins within co‐expression modules. Modules are listed along the x‐axis, and the height of the bar along the y‐axis indicates the proportion of significantly differentially expressed module members, while the color indicates the fold change according to the scale shown.
3. Module eigenprotein (the summary expression profile of a module) for 4 of the 15 modules generated by comparing C9Pos ALS and C9Neg ALS cases. The M6 module is significant, whereas other glial modules (M10 and M2) and a synaptic module (M8) are increased and decreased in C9Pos cases, respectively, yet do not reach significance using a Student's t‐test (P‐value listed above the plot). Box plots depict mean (horizontal bars) and variance (25^th to 75^th percentiles), with whiskers extending to the last non‐outlier measurements, as shown.