Fig. 2: Protein structures affected by the APOE genotype.
From: Structural signature of plasma proteins classifies the status of Alzheimer’s disease
a, Left: heatmap representing P values of β coefficients from multiple linear regression analysis assessing protein abundance-APOE genotype associations. Gray represents nonsignificant values. Right: Heatmap representing β coefficients showing the direction and magnitude of accessibility changes across APOE genotypes. The black boxes indicate peptides that were significant after false discovery rate correction (Padj < 0.05). b, Based on the STRING database, 22 proteins (gray circles) interact directly with APOE; three proteins (white circles) do not. Confidence cutoff = 0.4. The line colors represent the APOE genotype significantly associated with each protein. c, Unsupervised clustering based on the accessibilities of 91 labeled peptides with APOE genotype associations. Both clusters mainly included diseased individuals but were not disease-specific. d, APOE ε4/ε4 carriers showed significant C1QA structural changes (decreased GFCDTTNLKGLF accessibility) compared to the other genotypes (n = 13, 64, 47, 17 for ε3/ε2, ε3/ε3, ε3/ε4, ε4/ε4). The error bars represent the s.d. Kruskal–Wallis test with Dunn’s post hoc test: ε3/ε2 showed higher accessibility than all genotypes (P values: ε3/ε3, 0.037; ε3/ε4, 0.016; ε4/ε4, <0.001); ε4/ε4 lower than ε3/ε3 (P = 0.004) and ε3/ε4 (P = 0.012). *P < 0.05; ***P < 0.005; ***P < 0.0001 ApoE ε4/ε4 carrier. e, DVFEEGTEASAATAVKITLL (SERPINA3) accessibility showed bimodal distribution. The bar represents the percentage of individuals with accessibility <20% per APOE genotype. A Fisher’s exact test was used (P = 0.014); a pairwise Bonferroni correction identified group differences (*Padj = 0.024).
