Extended Data Fig. 7: MmV factor analysis (MOFA+) and brWB-CID validation of SRS1 IL1R2+ immature neutrophil expansion.

a-j MmV. a, Differentially expressed modules in whole blood bulk RNA-seq (FDR < 0.01, two-sided Wilcoxon rank-sum test) (n = 26 SRS1, n = 16 non-SRS1). Violin plots with median, 95% confidence interval and interquartile range. b, Enrichment of neutrophil related gene sets of weighted gene co-expression network analysis (WGCNA) modules upregulated in SRS1. c, Correlation (and 95% confidence interval) of module 10 eigengene expression with percentage of immature neutrophils from mass cytometry (CyTOF) per sample of mmV. d, Leading edge analysis for enrichment of scWB derived IL1R2+ immature neutrophil defining signature in module 10. e, IL1R2+ immature neutrophil (top) and cycling neutrophil progenitor (bottom) proportions following total leukocyte bulk transcriptomics deconvolution of n = 542 sepsis patients (brWB-CID microarray data)^5,18. Boxplots denote minimum and maximum with whiskers and bottom quartile, median and upper quartile with the box. f, Input data into MOFA+⁷⁷ model consisting of three modalities (105 plasma proteins, 33 module eigengenes (eigen) from WGCNA and 22 cell clusters from CyTOF) for n = 36 sepsis samples with one and six missing samples for CyTOF and plasma proteomics respectively. g, Scatter-plots of latent factor values for sepsis patients. h, Factor values by SRS groups (two-sided Wilcoxon rank-sum test) (n = 26 SRS1, n = 16 non-SRS1). Violin plots with median, 95% confidence interval and interquartile range. i, Variance decomposition showing percentage variance explained for individual modalities by each latent factor. j, Latent factor two weights per cell cluster (top) and gene module (bottom). k, Latent factor one weights per cell cluster (top) and gene module (bottom). SRS, sepsis response signature; Neu, neutrophil; imm neu, immature neutrophil; int inf neu, intermediate inflammatory neutrophil; pro-neu, pro-neutrophil; pre neu, pre-neutrophil; cMono, classical monocyte; ncMono non-classical monocyte; intMono, intermediate monocyte; cMono_1; Ki67⁺, cMono_2: CD163⁺CD354⁺Ki67⁺, cMono_3: CD163⁺, cMono_4: CD354⁺Ki67⁺. NES, normalized enrichment score; FDR, false discovery rate. * FDR < 0.05, ** FDR < 0.01, **** FDR < 0.0001, NS, not significant.