A Metabolomic Study To Identify New Globotriaosylceramide-Related Biomarkers in the Plasma of Fabry Disease Patients
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Bibliographic record
Abstract
Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A, which results in the progressive accumulation of glycosphingolipids. In addition to the two biomarkers, globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), which are routinely used for detection and high-risk screening of Fabry disease patients, novel urinary Gb3-related isoforms/analogues as well as newly defined lyso-Gb3 analogues in plasma and urine from Fabry patients have recently been described by our group. The aim of this study was to extend our recent analyses to identify and evaluate new potential Gb3-related biomarkers in the plasma of untreated male Fabry disease patients using a mass spectrometry metabolomic approach. A multivariate statistical analysis revealed five Gb3-related novel biomarkers in the plasma of male Fabry patients. Three of these new biomarkers correspond to Gb3, which has an extra double bond on the sphingosine with C16:0, C18:0, and C22:1 fatty acid chains. The fourth biomarker corresponds to a mixture of two structural isomers, the first with a d16:1 sphingosine and a C16:0 fatty acid and the second with a d18:1 sphingosine and a C14:0 fatty acid. To our knowledge, it is the first time that a Gb3 analogue with a d16:1 sphingosine moiety has been reported. In addition, this Gb3 analogue was also present in its methylated form. These biomarkers are part of a metabolic profile that may provide insight into the pathophysiology of Fabry disease.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it