Figure 1: Cohort Summary and Heterogeneity of ME/CFS. A) Cohort Design and ‘Omics Profiling.

96 healthy donors and 153 ME/CFS patients were followed over 3–4 years with yearly sampling. Clinical metadata including lifestyle and dietary surveys, blood clinical laboratory measures (N=503), gut microbiome (N=479), plasma metabolome (N=414), and immune profiles (N=489) were collected (Supplemental Table 1 and Supplemental Figure 1A). B) Heterogeneity and Non-Linear Progression of ME/CFS in Symptom Severity and ‘Omics Profiles. Variability in symptom severity (top) and ‘omics profiles (bottom) for 20 representative ME/CFS patients over 3–4 time points. For symptom severity, the 12 major clinical symptoms (x-axis) vs. severity (scaled from 0% to 100%, y-axis) is shown for each patient (each color), with lines showing average severity and shaded areas showing severity range over their timepoints. The widespread highlights the lack of consistent temporal patterns and unique symptomatology of ME/CFS (controls shown in Supplemental Figure 1C). Bottom, PCoA of integrated ‘omics data with color dots matching patient timepoints in the symptom plot and grey dots representing the entire cohort. Again, the spread and overlap of the colored space reflect the diversity in ‘omics signatures vs. the more consistent pattern typical of controls (Supplemental Figure 1B). Abbreviations: ME/CFS, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; PCoA, Principal Coordinates Analysis. Supporting Materials: Supplemental Table 1, Supplemental Figure 1.