Platelet RNA-seq analysis shows extensive gene expression differences with upregulation of translation and transcription pathways in SLFN14 K219N carriers. (A) Dotplot showing the RIN value vs rRNA ratio of platelet RNA-seq samples from SLFN14 patients IV.2 and III.4, 19 healthy controls, and 26 unrelated, undiagnosed patients with a platelet function (PF) defect or TP. (B) Principal component (PC) analysis plot based on the top 500 genes with the highest variance among samples. (C) Boxplot showing tmm-normalized counts for SLFN14 in patients IV.2 and III.4 and 20 controls as detected by total RNA-seq. Boxplots represent the middle 50% of the data points with, 25% outliers as whiskers and the mean as a black horizontal line. (D) Heatmap showing tmm-normalized counts for all expressed (>10 reads on average in the control group) mitochondrial (M) RPGs and RPGs in patients IV.2 and III.4 and controls. Statistics were performed using the Wilcoxon test. (E) A gene-gene association network for all significantly upregulated genes (log2 fold change >1, false discovery rate <0.05) in platelets from patients IV.2 and III.4, created in Cytoscape. Five subnetworks among the 2762 nodes were identified in the largest connected network. The zoom-in images show the mitochondrial RPGs (green) and RPGs (light blue). TCA, tricarboxylic acid.