Differentially expressed proteins make up the transcription factor mutant platelet proteome. (A) Principal component analysis shows clustering of control samples from 28 individuals, clearly separated from GFI1B^Q287* mutant-derived platelets (PC1). RUNX1 and GATA1 mutant platelets are more similar to each other and controls compared with GFI1B mutant platelets. (B) Hierarchical clustering was observed between control and mutant-derived platelets by K-means clustering analysis. One GFI1B case maps between a GATA1 and RUNX1 case and 1 control case maps between 2 RUNX1 cases. The differentially expressed proteins were subdivided into 3 clusters based on their expression similarity. Cluster 1 represents proteins that are mainly downregulated in mutants compared with controls. Cluster 2 represents proteins that are upregulated in GATA1^R216Q and RUNX1 mutants compared with controls. Cluster 3 shows upregulated proteins for GFI1B^Q287* mutant platelets. Downregulated proteins are marked in red; upregulated proteins are marked in blue. (C) Venn diagram from downregulated proteins shows overlap on affected proteins between TF mutants, but none are common to all TFs. Numbers in the different areas indicate the amount of shared proteins between cases. Proteins converging to significantly underrepresented processes are listed in supplemental Tables 2F and 4. (D) Venn diagram from upregulated proteins shows overlap of common upregulated proteins, but none are common to all TFs. Proteins converging to significantly overrepresented processes are listed in supplemental Tables 2H and 4. The total number of proteins down- and upregulated for RUNX1 variants was 65 + 47 = 112, whereas only 10 + 1 = 11 proteins were in common.