Figure 1 | Scientific Reports

Figure 1

From: Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation

Figure 1

Individuals with trisomy 21 display consistent differences in their circulating proteomes. (a) Volcano plots displaying the results of a SOMAscan® proteomics analysis for 3,585 epitopes detected in plasma samples from individuals with or without trisomy 21 (T21). This cohort, referred to as the Discovery Study, involved 120 individuals with T21 and 52 euploid (D21) controls. Adjusted p-values [p(a)] were generated with the Kolmogorov-Smirnov test using a Bonferroni correction for multiple hypothesis testing. When using a cut-off of p(a) <0.1, 178 proteins were identified as significantly downregulated in people with T21 (e.g. Immunoglobulin E, IGHE) versus 121 upregulated proteins (e.g. β-2-microglobulin, B2M). Green dots indicate the 50 proteins encoded in chromosome 21 (chr21) for which aptamers were available in the SOMAscan® assay, only 9 of which passed the p(a) <0.1 cut-off (e.g. TFF3). (b) For comparison purposes, data in (A) was re-analyzed to identify differences between females and males. KLK3, downregulated in females, is the prostate-specific antigen (PSA). CGA, upregulated in females, is the alpha subunit of the follicle stimulating and luteinizing hormones. (c) Manhattan plot of all detected proteins showing that most differential proteins observed are not encoded on chr21 (top). Individual Manhattan plots showing the proteins encoded on chr14, chr15 and chr21 are shown at the bottom. Red dashed line indicates a zero-fold change. Significantly different proteins are defined as p(a) < 0.1 using KS test with Bonferroni correction. (d) Box and whisker plots showing the comparative results for B2M and IGHE in the Discovery Study and two smaller Validation Studies. Adjusted p-values shown from KS test with Bonferroni correction for the Discovery Study and Benjamini-Hochberg for the smaller Validation Studies. See also Figs 1S1 and S2. (e) Metascape analysis of significantly differential proteins in the Discovery Study, as defined by p(a) <0.1, 299 proteins in total. Each node represents a GO term, KEGG pathway, or Reactome gene set. The 3,585 proteins detected by SOMAscan® assay were used as the background gene set. See also Figs 1S3, 1S4, and Supplementary File 2.