Fig. 8: N-terminome and proteome in NAA10-mutant iPSC-CMs.
From: Dysregulation of N-terminal acetylation causes cardiac arrhythmia and cardiomyopathy
a The first amino acids enriched by Nt-peptide enrichment. b Sequence logos of the first 5 amino acids of NatA-subject peptides. c Sequence logos of the first 5 amino acids of peptides which were not subject to the cleavage of methionine aminopeptidase. d Representative mass spectra of Nt-acetylated MYH7. e Gene Ontology of Biologic Processes (GOBP) terms for enriched Nt-acetylated proteins. f Scatter plot of the Nt-acetylated proteins with the relative ratio of Nt-acetylated peptides normalized by total protein. Each protein was ranked according to the order of the relative ratio. Proteins known as causative to heart diseases are highlighted in red. g The normalized relative ratio of Nt-acetylated peptides from f., showing a significant reduction in Nt-acetylation in eNAA10R4S/Y-iPSC-CMs (−0.25 ± 0.08; mean ± SEM; p = <0.0001; one sample Wilcoxon test). h Volcano plot of total proteins. The cut-off value was set to 0.5 or −0.5 for log2(fold change), and 1.0 for log10(FDR). Upregulated proteins with statistical significance were highlighted in red, and downregulated proteins were highlighted in blue. i Representative gene set enrichment analysis (GSEA) plot of the running enrichment score for an upregulated GOBP term (GO:0033275, actin_myosin_filament_sliding). j Representative GSEA plot of the running enrichment score for a downregulated GOBP term (GO:0006096, glycolytic_process). k The results of GSEA for GOBP terms. GSEA was performed by a one-sided permutation test. The Benjamini-Hochberg method was applied to correct multiple comparisons. GOBP terms with an adjusted P-value (Padj) less than 0.05 are listed. Gene ranks depict the ranked list metric, and NES represents normalized enrichment score. ****p < 0.0001. Source data are provided as a Source Data file.
