Fig. 3 |. Multi-omics analyses reveal iRHOM2 function in humans.

a, Results of cytokine array. The results are shown by heat map based on the ratio between patients and HCs (left panel). Actual data of IL-8, eotaxin-1 and IL-1β are shown (right panel, n = 4 for each HC and patient group). Data are mean ± s.d. and were analyzed by two-tailed, unpaired Student’s t-test. b, GSEA of the patient whole-blood RNA-seq data in comparison with HCs after redundancy reduction. GSEA of differentially expressed genes in HCs versus patients. c, Results for the ‘neutrophil-mediated immunity’ gene set in GSEA. Enrichment plot and heat map for individual genes in the gene set are shown. NES, normalized enrichment score. d, Mean normalized counts comparing averages of patient and HC T cells for each highlighted gene set in Extended Data Fig. 3g (n = 4 per group). Error calculated is s.e.m. e, Heat map indicating the time course of gene expression for genes with significant differences between four HCs and four patients at 3 h of stimulation. Gene expression is shown as normalized counts of mRNA plotted along a scale, where blue indicates low counts and red indicates high counts. Enrichment map of biological processes in the yellow square with connections between nodes signifying at least 65% overlap among the genes assigned to each node. f, Scatter plot of principal component axis one (PC1) and axis two (PC2) based on lipidomics data. Individual data points are colored according to patients and HCs and shading shows clusters. g, Cluster analysis of lipidomics data. Three technical repeats results are shown by heat map (left). Each specific lipid level of patients in comparison with the HCs is shown (right). Fractions of identified lipid species increased, decreased or no change (bottom). Statistical significance of the enrichment score was calculated by using an empirical phenotype-based permutation test (b,c). Pt, patient.