Fig. 2: Differential expression analysis of persons with MS (pwMS) compared to healthy controls (HC) in cerebrospinal fluid (CSF) and plasma.

a Principal component (PC) analysis of all proteins measured in the CSF samples (left) and plasma samples (right). b Volcano plots showing differentially expressed proteins (DEPs) in CSF (left) and plasma (right). The top upregulated proteins, which overlapped in discovery cohort and replication cohort, are marked with protein names in the plots. The differential expression analysis was performed using a two-sided linear model t-test (Limma analysis). c DEPs (false discovery rate < 0.05) in the CSF, in either the discovery cohort or the replication cohort. The first two columns show the log2 fold change (FC) of the DEPs in each cohort. Most proteins are upregulated (red) and 23 proteins overlap in discovery and replication cohorts. In the three columns to the right, it is marked which proteins are in three different list of known MS-associated genes and proteins (DisGeNET database, GWAS genes, and MS biomarkers) with the odds ratio of the enrichment shown on the top (two-sided Fisher’s exact test). The DEPs were significantly enriched for MS-associated genes from DisGeNet (discovery: p = 7∗10−8, replication: p = 0.002), GWAS (discovery: p = 1∗10−7, replication: p = 2∗10−4), and known MS biomarkers (discovery: p = 1∗10−12, replication: p = 2∗10−6).