Extended Data Fig. 2: Exposure to pro-inflammatory cytokines drives changes in the transcriptome and proteome of pancreatic β cells.

a, Volcano plot of RNA-seq genes, showing up-regulated genes (green) and down-regulated genes (red) upon exposure of EndoC-βH1 to cytokines. Vertical lines indicate the log₂ fold change threshold (absolute log₂ fold change > 1) and horizontal line indicates the FDR adjusted P cutoff for significance (FDR adjusted P < 0.05) calculated by fitting a negative binomial model in DESeq2. b, Distribution of RNA-seq counts in human islet samples in the genes previously classified as up, down or equal-regulated in EndoC-βH1 cells. Boxplot limits show upper and lower quartiles, whiskers extend to 1.5 times the interquartile range and the notch represents the confidence interval around the median. c, Volcano plot for multiplex proteomics, showing in green the up-regulated proteins and in red the down-regulated, which have a Q-value < 0.1 and absolute log₂ fold change > 0.58. Vertical lines indicate the log₂ fold change thresholds. d, Protein-protein Interaction (PPI) network generated from up-regulated proteins after cytokine exposure. Node color indicates belonging to same interacting community and background corresponds to specific pathway enrichment. e, Proportion of up, equal or down-regulated proteins encoded by genes located <15 kb from IREs or SREs. *** Chi-squared test P < 0.001. f, An additive effect on gene up-regulation was observed for multiple IREs located at <40 kb of a gene. Box plot limits show upper and lower quartiles, whiskers extend to 1.5 times the interquartile range and the notch represents the confidence interval around the median. ANOVA P < 2.2 × 10⁻¹⁶. g, View of the LY6E locus, whose expression is induced after cytokine exposure and is coupled with chromatin changes in the vicinity.