Proteomic landscape of platelets from controls and patients before and after treatment. (A) Volcano plot comparing the platelet proteomes of patients with sitosterolemia before treatment and healthy controls. Upregulated proteins in patients are shown in orange, whereas downregulated proteins are shown in blue. (B) Volcano plot comparing proteomic profiles of patients before and after treatment. Upregulated proteins after the treatment are shown in red. (C) Volcano plot comparing the platelet proteomes of patients with sitosterolemia after treatment and healthy controls. Upregulated proteins in patients are shown in red, whereas downregulated proteins are shown in dark blue. (A-C) Circles are drawn around granule-derived proteins: purple = alpha granules; green = dense granules. The difference in the expression is shown on the x-axis, and the logarithmic P value (–log(P value)) is shown on the y-axis. Dotted lines indicate the threshold of significance with the horizontal line marking a –log10 (adjusted P value) of 1, and the vertical dotted lines marking a log2(fold change) of 1. For a complete list of the significantly regulated proteins, refer to the supplemental Tables. (D) Heat map of Pearson correlation coefficient of the pairwise comparison of all quantified proteins in this study. The row and column splits are based on WGCNA-defined functional modules, which are numbered. Color gradients denote coefficients (purple: −1, white: 0, orange:1). A heat map of the median module intensity per condition is annotated below. Colors reflect the LFQ intensity. (E) GO term enrichment of functional modules. Color indicates module, node size indicates amount of proteins with a GO term annotation, and edge width denotes GO term similarities based on Jaccard’s similarity. (F-G) Box plots showing protein intensities (LFQ) of a selection of proteins in module 8 associated with an inflammatory response (F) or blood microparticles (G). The black dots represent the individual measurements.