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Fig. 7 | Journal of Translational Medicine

Fig. 7

From: ALS blood expression profiling identifies new biomarkers, patient subgroups, and evidence for neutrophilia and hypoxia

Fig. 7

Myeloid and lymphoid ALS patient subgroups. a Cell type signature scores and hazard ratios (HRs). Scores were calculated by averaging Z-score normalized expression of the 100 genes most specifically expressed in each cell type (or the 100 genes most strongly induced with acute high altitude stress; see Methods). Heatmap rows and columns are clustered (rows: 1–correlation; columns: Euclidean distance; right: hazard ratios; covariates: age, sex, site of onset, and cohort; n = 396 patients). b Myeloid and lymphoid patient subgroups. Myeloid signatures were calculated for each patient by averaging DC, MP, MC, NP, PL, RBC and ES scores, and lymphoid signatures were calculated by averaging CD8, CD4, GDT, NK and B scores. Each symbol represents an individual patient (myeloid group: myeloid score > 0.05 and lymphoid score < − 0.05; lymphoid group: myeloid score < − 0.05 and lymphoid score > 0.05; green line: robust regression estimate). c Genes with strongest expression differences in myeloid and lymphoid group patients. d Interleukin genes. In c, d, boxes or error bars span the middle 50% of Z-score normalized expression values in each group (median: midline or circle). e IL6R expression. f IL23A expression. In e, f, symbol colors denote expression of IL6R and IL23A, respectively. g Inflammation-associated genes. The standardized mean difference (SMD) is shown for each gene (red triangle: genes with higher expression in “high inflammation” ALS patients; blue triangle: genes with higher expression in “low inflammation” ALS patients; see Figure 1A from Mizwicki et al. [42]). Gene labels with an asterisk (*) had detectable expression in fewer than 20% (< 42/210) of patients from the myeloid and lymphoid groups. h High inflammation gene GSEA analysis. Genes are ranked according to their expression difference in myeloid versus lymphoid patients (horizontal axis) and cumulative abundance of high inflammation genes is shown (vertical axis) (p-value: Wilcoxon rank sum test). The analysis excludes genes with low expression (*)

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