Fig. 4
From: Heparin-enriched plasma proteome is significantly altered in Alzheimer’s disease
Heparin enrichment enhances the depth of plasma proteome and is reproducible. A The second replication dataset (Set 2) was comprised of control (n = 36) and AD individuals (n = 49), which underwent similar heparin enrichment and TMT-MS analysis as the discovery dataset (Set 1). B The combined datasets yielded a total of 3284 unique proteins, and 2866 of them being identified and quantified in 50% or more of the samples (< 50% missing) across two sets. Set 1 and Set 2 identified 2077 and 2618 proteins respectively, with 50% missing. C The 2866 proteins were ranked by their log2 estimated concentration (pg/L) in plasma. Protein concentration information was obtained from The Human Protein Atlas Database. Notably, this set of proteins covered an impressive range of concentrations, spanning 10 orders of magnitude. Even proteins with the lowest concentration, such as LAG3 and RNF213, were included, along with numerous members of the M42 matrisome that are highlighted. D The number and overlap of proteins quantified in Set 1 (N = 2077) and Set 2 (N = 2618) with less than 50% missing values. Among the 2866 total unique proteins identified, approximately 64% (1829 out of 2866) were overlapping between the datasets. E A scatter plot illustrates the Pearson correlation between log2 fold-change (AD vs CTL) of significantly altered proteins in both Set 1 and Set 2. There’re 732 proteins overlapping in the two sets and being significantly changed in AD with a BH FDR-corrected p-value < 0.05 in both datasets. Only 10 out of 732 proteins exhibited discordant changes in the two sets, demonstrating a high degree of concordance (cor = 0.93, p < 1e−200). Furthermore, all 390 overlapping proteins selected with a BH FDR-corrected p-value < 0.01 displayed consistent changes in both datasets when comparing AD and control samples, with a remarkable correlation of 0.96 (p < 1e−200). The significance of Pearson correlation was determined by Student’s t-test. CTL, control; LC–MS, liquid chromatography-mass spectrometry; cor, Pearson correlation coefficient