A 3D-genomic blood test identified patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome with 96% accuracy in an independent validation cohort.
The EpiSwitch CFS test achieved 92% sensitivity and 98% specificity in distinguishing patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from healthy controls. Researchers reported 22 true positives, 44 true negatives, 2 false negatives, and 1 false positive. The model incorporated 200 chromosomal conformation markers linked to immune and inflammatory pathways involving interleukin-2, IL-10, TNF/NF-kappaB, toll-like receptor, and JAK/STAT signaling.
“By mapping the top 3D genomic biomarkers to the closest genetic loci captured by their topological control (within 3Kb), it is possible to broaden the biological insights into genes, pathways and protein networks under the influence of 3D genomic regulation and associated cellular phenotype, contributing to the pathology of a disease and identify potential therapeutic strategies,” said Edward Hunter, PhD, of Oxford BioDynamics Plc, Oxford, UK, and colleagues.
The retrospective case–control study analyzed whole-blood DNA from patients aged 20 to 80 years. Forty-seven severe housebound ME/CFS cases and 61 controls used for initial profiling, and 24 cases with 45 controls for validation. Microarray analysis measured approximately 1 million chromosomal markers per sample. After normalization and feature selection using limma and Rank Product algorithms, 200 key markers trained an XGBoost machine-learning classifier. Pathway enrichment analysis using the STRING database identified affected immune networks.
Participants with autoimmune disease, cancer, or other chronic illnesses were excluded. Researchers noted that the modest sample size and single-country cohort limited generalizability, emphasizing the need for validation in larger, multi-center studies.
The authors concluded that consistent chromosomal conformation patterns in blood DNA may clarify the biological basis of ME/CFS and aid in developing objective diagnostic tools.
The study was funded by Oxford BioDynamics plc. Researchers Edward Hunter, PhD, Hanan Alshaker, PhD, Olga Bundock, PhD, David Kerr, PhD, and Alexandre Akoulitchev, PhD, were employees of Oxford BioDynamics during the study. Other contributors declared no competing interests.
The study was approved by the UK National Research Ethics Service, and all participants provided written informed consent.