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Publications Preprint 5 min

Exploratory Dried Blood Spot Metabolomics Identifies Pathway-Level Convergence with ME/CFS Biology in a Self-Reported PEM-Like Fatigue Phenotype

Preprint by Hauguel, Anctil, and Noel showing that dried blood spot metabolomics in 1,784 adults captures the same carnitine, TCA-cycle, redox-thiol, and tryptophan-kynurenine pathways previously implicated in ME/CFS plasma studies, scaling with symptom severity.

Pierrick Hauguel, Nicolas Anctil, Louis-Philippe Noel ·
fatigueME/CFSmetabolomicsdried blood spotspreprint

Why it matters

Shows that BioTwin's same single-laboratory dried blood spot LC-MS platform, validated for individual identification and breast cancer detection, also captures fatigue-associated metabolic biology at a scale no prior plasma cohort has reached, supporting at-home self-collected DBS as a platform for future clinically adjudicated validation.

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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).

  1. 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.

Important: This article may discuss BioTwin research, medical vision, regulated clinical pathways, or TwinMe wellness education. TwinMe wellness outputs are not medical or laboratory tests. BioTwin clinical outputs are available only where authorized and through licensed healthcare professionals.