Summary
A community cohort of 1,784 adults was profiled from fingerstick dried blood spots (DBS) by reverse-phase LC-MS using paired 5-minute and 15-minute gradients. A biology-first panel of 22 literature-curated metabolites, curated from prior ME/CFS plasma and serum studies, achieved out-of-fold AUC 0.81 for a pragmatic self-reported post-exertional-malaise (PEM)-like fatigue endpoint (226 cases / 914 controls).
Stable contributors mapped to the carnitine-shuttle, TCA-cycle, redox-thiol, and tryptophan-kynurenine pathways, the same metabolic axes repeatedly implicated in plasma and serum ME/CFS metabolomics. The metabolomic score increased with symptom severity (Spearman rho = 0.45), remained robust to adjustment for age, sex, BMI, and medication burden, and produced a metabolomic-specific lift of roughly 0.13 AUC over the strongest anti-leakage questionnaire baseline. Paired 5-minute and 15-minute gradients showed directional concordance (Pearson r = 0.62 for signed univariate effects).
This is an exploratory study. The findings should not be interpreted as clinical validation of a diagnostic test, screening tool, or objective provoked-PEM biomarker.
Why it matters
This is the fatigue counterpart to BioTwin’s individual-identification and breast-cancer work: the same minimally invasive, self-collected DBS matrix and the same single-laboratory LC-MS protocol, now applied to a self-reported PEM-like fatigue phenotype. The fingerstick DBS format is compatible with home self-collection without phlebotomy, which is operationally relevant in fatigue and PEM-like syndromes where repeated clinic attendance can be burdensome for the most affected individuals.
No prior published plasma ME/CFS cohort has exceeded 200 cases; profiling 1,784 adults across orthogonal LC gradients in the same individuals is a substantially larger and more analytically controlled assessment. The convergence with previously reported metabolic axes supports DBS metabolomics as a biologically grounded platform for future clinically adjudicated validation, decision-support development, and longitudinal monitoring.
Status
Preprint posted on medRxiv (DOI: 10.64898/2026.06.08.26355197). The full draft is also available for download above.
Authors
Pierrick Hauguel (1), Nicolas Anctil (1), Louis-Philippe Noel (1). Corresponding author: Pierrick Hauguel (phauguel@biotwin.ai).
- Research and Development Department, BioTwin Inc., Quebec City, QC, Canada
Competing interests: Pierrick Hauguel, Nicolas Anctil, and Louis-Philippe Noel are employees and shareholders of BioTwin Inc.