Fig. 3: Defining a gene signature of platelet hyperreactivity: Platelet Reactivity Expression Score (PRESS).

A, B To generate a platelet hyperreactivity gene signature, platelets were collected from PACE-PAD patients before lower extremity revascularization (LER, n = 129). Platelet RNA-seq and stratification of patients by hyperreactive platelet responses (aggregation responses > 60% versus = 40% to 0.4 µM epinephrine, n = 84). Violin plots showing platelet aggregation distribution, median represented by the bold dashed line and IQR by dashed lines. P < 0.001 as determined by a 2-sided Mann-Whitney U-test. C, D Overlap of transcripts differentially expressed (using both DESeq2 Wald test and the Wilcoxon rank-sum test after adjustment for age, sex, and race/ethnicity) between patients with hyperreactive or not hyperreactive platelets (n = 796), and transcripts significantly correlated with platelet aggregation responses to 0.4 µM epinephrine (n = 2035). Overlapping genes, n = 451 (PRESS gene set), 174 transcripts positively and 277 transcripts negatively associated with platelet hyperreactivity. E Boxplot showing the platelet hyperreactivity signature score in 10-fold cross-validation training comparing hyperreactive platelet and not hyperreactive platelet patient groups. The line across the box indicates the median, with the whiskers extending to ±1.5 × IQR following z-score normalization. Each outlier outside the whiskers are represented by individual marks. n = 84. F Receiver operating characteristic (ROC) curve of the mean 10-fold cross-validation training of the hyperreactive platelet signature, the shaded areas represent 95% CIs plotted for sensitivity at given in-sample specificities. Source data are provided as a Source Data file. Panel A created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.