Proteome analysis of cultured microglia identified TNF-α as a candidate regulator of the response to myelin debris. (A) Volcano plot of regulated proteins in vehicle-treated Myd88−/− versus vehicle-treated WT. (B) Volcano plot of regulated proteins in myelin-treated Myd88−/− versus myelin-treated WT. The negative log10 transformed P value is plotted against the log2 transformed LFQ intensity ratios for each protein. Proteins with a P value <0.05 are indicated as red circles, whereas proteins with a P value >0.05 are indicated as blue circles. The hyperbolic curves indicate the threshold of a permutation-based FDR correction for multiple hypotheses (FDR: P = 0.05, s0 = 0.1). (C) Heat map of the top 35 regulated proteins, which were consistently quantified in all comparisons. The log2 fold changes of the proteins are indicated in a color scale from blue to red. (D) Heat map of significant upstream regulators predicted by Ingenuity Pathway Analysis. The negative log10 P value was multiplied with the sign of the related z-score. Blue color indicates a decreased activation, whereas red color indicates an increased activation with the corresponding upstream regulator.