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MOESM15 of ALS blood expression profiling identifies new biomarkers, patient subgroups, and evidence for neutrophilia and hypoxia

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posted on 22.05.2019 by William Swindell, Colin Kruse, Edward List, Darlene Berryman, John Kopchick
Additional file 15. Cell type enrichment (ImSig algorithm). (A) Cell type ranking. Grey boxes outline the middle 50% of ImSig cell type scores for CTL subjects (n = 645; middle line: median). Magenta bars span the middle 50% of ImSig scores for ALS patients (n = 396; circle: median). P-values obtained from the test of an ALS vs. CTL score difference are listed (right margin; two-tailed t-test; red: FDR < 0.05 with ALS > CTL; blue: FDR < 0.05 with CTL > ALS). Cell type scores (horizontal axis) were normalized using a Z-score transformation and combined across the two cohorts (GSE112676 and GSE112680). (B) Neutrophil score histograms. (C) Translation score histograms. In (B) and (C), cell type scores from each cohort (GSE112676 and GSE112680) were normalized using the Z-score transformation and expression values from the two cohorts were combined. Boxplots (top margin) outline the middle 50% of expression values in each group (whiskers: 10th to 90th percentile; p-values: two-tailed t-test). (D) Top 40 neutrophil signature genes with lowest p-value (ALS vs. CTL). (E) Neutrophil signature gene GSEA analysis. (F) Top 40 translation signature genes with lowest p-value (ALS vs. CTL). (G) Translation signature GSEA analysis. (H) Top 40 macrophage signature genes with lowest p-value (ALS vs. CTL). (I) Macrophage signature GSEA analysis. In (D), (F) and (H), red bars/font indicates ALS-increased DEGs (FDR < 0.10 with FC > 1.10) and blue bars/font indicates ALS-decreased DEGs (FDR < 0.10 with FC < 0.91). The pie chart (upper right) indicates the proportion of genes not significantly altered in the ALS vs. CTL comparison (black), ALS-increased DEGs (red) and ALS-decreased DEGs (blue). In (E), (G) and (I), genes are ranked based upon their expression difference in ALS vs. CTL subjects (horizontal axis), and cumulative overlap of cell type signature genes is shown (vertical axis) (p-value, lower right, Wilcoxon rank sum test).