Fig. 3: Network construction elucidates subtype-specific disease pathways and eigengenes associated with ALS patient clinical outcomes.

a Network of pathways associated with the ALS cohort, color coded by subtype, with maroon indicating ALS-TD, navy denoting ALS-Ox, and gold signifying ALS-Glia. b WGCNA identifies gene subsets significantly correlated with ALS patient age of disease onset, age of death, and disease duration (univariate regression, two-tailed). Eigengene labels, moving left to right in the dendrogram, are: pink, red, tan, navy (ALS-Ox), brown, green, gold (ALS-Glia), gray, maroon (ALS-TD), yellow, blue, salmon, black, and green-yellow. Eigengenes were enriched for gene ontology and Bonferroni-adjusted p-values are shown (Fisher’s exact test, one-sided). Subtype-specific expression of eigengenes was determined using dummy regression (two-tailed), with the β coefficient presented as a heatmap. A positive β coefficient denotes subtype upregulation of transcripts comprising the particular eigengene. Bonferroni-adjusted p-values less than 0.05 are denoted with *. c Univariate plots showing gene expression levels of four features (FCGR1B, FCGR3A, HLA-DOA, SERPINA3) in the gold eigengene – with evidence for ALS-Glia specificity. P, DESeq2¹⁴ differential expression using the negative binomial distribution, two-tailed, false discovery rate (FDR) method for multiple hypothesis test correction. d ALS-TD specific expression of four representative features (ENSG00000215068, ENSG00000248015, KRT8P42, LINC00639) in the maroon eigengene. P, same as c. Source data are provided as a Source Data file.