Fig. 2: Multi-omics analyses comparing ME/CFS vs. HC.
Metabolomics. BayesFactors (BFs) of 913 metabolites in plasma comparing ME/CFS vs. HC (A) before and (B) 24 h after exercise, using linear mixed-effect models (LMMs) paired with Bayesian analyses. The LMM models were adjusted for age, sex, race/ethnicity, geography, body mass index (BMI), and self-reported irritable bowel syndrome (sr-IBS). Significant metabolites were labeled (significance defined as 1. FDR adjusted p < 0.05, or 2. BF > 3 and 95% HDI does not cover 0, or 3. BFcombined > 10 and HDIcombined does not cover 0). If BFcombined > 10 and BFcombined > BF, BFcombined is plotted, otherwise, BF is plotted. Gray dots at the bottom of the figure represent individual metabolites that were not significantly altered between ME/CFS and HC. The significant chemical clusters identified by ChemRICH were individually labeled. The significant metabolites in other nonsignificant clusters were labeled under “Other” on the right. The full metabolomic results, comparing ME/CFS and HC, are reported in Supplementary Data 3A. Scatter plots showing BayesFactors (BFs) associated with changes in plasma levels of metabolites from before to 24 h after exercise in (C) ME/CFS and in (D) HC. The full metabolomic results, comparing ME/CFS and HC, are reported in Supplementary Data 3A. Proteomics. Volcano plots showing BayesFactors (BFs) of proteomic analytes in plasma comparing ME/CFS vs. HC (E) before and (F) after exercise, using linear mixed-effect models (LMMs) paired with Bayesian analyses. The LMM models were adjusted for age, sex, race/ethnicity, geography, body mass index (BMI), and self-reported irritable bowel syndrome (sr-IBS). Significant proteins were labeled (significance defined as 1. FDR adjusted p < 0.05, or 2. BF > 3 and 95% HDI does not cover 0). Gray dots at the bottom of the figure represent individual proteins that were not significantly different between ME/CFS and HC. The full proteomic results, comparing ME/CFS and HC, are reported in Supplementary Data 6A. Integrative enrichment. Ingenuity pathway analyses (IPA), combining plasma metabolomic and proteomic results, comparing ME/CFS vs. HC (G) before and (H) after exercise. The full IPA results, comparing ME/CFS and HC, are reported in Supplementary Data 7A. I Citric acid and ratios of metabolites. Box plots showing levels of citric acid and standardized ratios of ornithine (ORN) to citrulline (CIT), arginine (ARG) to citrulline (CIT), kynurenine (KYN) to tryptophan (TRP) and kynurenic acid (KYNA) to kynurenine (KYN) in ME/CFS and HC before and 24 h after exercise. Comparisons employed linear mixed-effect models (LMMs) paired with Bayesian analyses, adjusted for age, sex, race/ethnicity, geography, body mass index (BMI), and self-reported irritable bowel syndrome (sr-IBS). The full results from ratio analysis, comparing ME/CFS and HC, are reported in Supplementary Data 4A.
