Figure 4.
Absolute quantification of the activated platelet lipidome reveals arachidonic acid metabolism as the most dynamic network. (A) Regulated and nonregulated lipid species numbers across different stimuli. (B) Venn diagram of significantly regulated lipid species in wild-type platelets across 3 different types of activation (thrombin, CRP, thrombin + CRP). (C) Scatter plots displaying selected examples of pairs of lipids whose relative abundance is either positively (top left panel) or negatively (top right panel) correlated. Black lines indicate linear fit (bottom panel). Analysis of the fraction of correlations connecting lipids of the same lipid class (red) or different lipid classes (blue), as function of correlation strength. (D) Hierarchical clustering of the lipid-lipid correlation and anticorrelation matrix. Rows and columns correspond to the 384 quantified lipid species. Black boxes indicate clusters of strongly correlated and anticorrelated lipids. Lipid cluster numbers are indicated on the right. (E) Number of lipids in each cluster sorted by lipid class. (F) Network visualization of the lipid-lipid correlations. Edges are correlations of r ≥ 0.85. Nodes are lipids. Node size represents the degree of connectivity and the node color represents the analyzed lipid class (see inset). (G-I) The network during activation by thrombin, CRP, or thrombin + CRP; pure red indicates a fold ≥2 and pure green a fold change ≤0.5. Data are combined from 3 independent biological experiments and mean values are shown.