AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.
Document Type
Article
Publication Date
9-1-2025
Original Citation
Xiong R,
Aiken E,
Caldwell R,
Vernon S,
Kozhaya L,
Gunter C,
Bateman L,
Unutmaz D,
Oh J.
AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome. Nat Med. 2025;31(9):2991–3001.
Keywords
JGM, SS1, Humans, Fatigue Syndrome, Chronic, Male, Female, Metabolomics, Adult, Biomarkers, Gastrointestinal Microbiome, Middle Aged, Artificial Intelligence, Metabolome, Neural Networks, Computer, Longitudinal Studies, Metagenomics, Multiomics
JAX Source
Nat Med. 2025;31(9):2991–3001.
ISSN
1546-170X
PMID
40715814
DOI
https://doi.org/10.1038/s41591-025-03788-3
Grant
his work was funded by 1U54NS105539. R.X., E.A., R.C., S.D.V., L.K., C.G., L.B., D.U. and J.O. were funded by 1U54NS105539. J.O. is additionally supported by the NIH (1 R01 AR078634-01, DP2 GM126893-01, 1 U19 AI142733, 1 R21 AR075174).
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness with a multifactorial etiology and heterogeneous symptomatology, posing major challenges for diagnosis and treatment. Here we present BioMapAI, a supervised deep neural network trained on a 4-year, longitudinal, multi-omics dataset from 249 participants, which integrates gut metagenomics, plasma metabolomics, immune cell profiling, blood laboratory data and detailed clinical symptoms. By simultaneously modeling these diverse data types to predict clinical severity, BioMapAI identifies disease- and symptom-specific biomarkers and classifies ME/CFS in both held-out and independent external cohorts. Using an explainable AI approach, we construct a unique connectivity map spanning the microbiome, immune system and plasma metabolome in health and ME/CFS adjusted for age, gender and additional clinical factors. This map uncovers altered associations between microbial metabolism (for example, short-chain fatty acids, branched-chain amino acids, tryptophan, benzoate), plasma lipids and bile acids, and heightened inflammatory responses in mucosal and inflammatory T cell subsets (MAIT, γδT) secreting IFN-γ and GzA. Overall, BioMapAI provides unprecedented systems-level insights into ME/CFS, refining existing hypotheses and hypothesizing unique mechanisms-specifically, how multi-omics dynamics are associated to the disease's heterogeneous symptoms.