Multiplex Tandem Mass Spectrometry Analysis of Novel Plasma Lyso-Gb<sub>3</sub>-Related Analogues in Fabry Disease
Bibliographic record
Abstract
Fabry disease is a multisystemic, X-linked lysosomal storage disorder caused by a deficit in α-galactosidase A enzyme activity leading to glycosphingolipid accumulation, mainly globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). Recent metabolomic studies have led to the discovery of novel biomarkers related to lyso-Gb3 in plasma and urine. These biomarkers show modifications of the sphingosine moiety of the lyso-Gb3 molecule. The objectives of this study were to develop and validate a liquid chromatography-tandem mass spectrometry method for the relative quantification of novel plasma lyso-Gb3-related analogues, to evaluate their levels in plasma of 74 Fabry patients and 41 healthy controls and to correlate these results with patient gender, enzyme replacement therapy treatment, and lyso-Gb3 analogue levels previously measured in urine for the same patients. As expected, the concentrations of lyso-Gb3 and its related analogues in plasma are higher in Fabry males compared to Fabry females and higher for untreated males compared to treated males. The concentration of lyso-Gb3 and its related analogues in plasma decrease significantly after the beginning of enzyme replacement therapy (ERT) treatment and remain stable for 30 months of monitored therapy in a Fabry male. In plasma, lyso-Gb3 is significantly more abundant than its related analogues, which differs from urine where the majority of the lyso-Gb3 analogues are more increased than lyso-Gb3 itself. In contrast to urine, the relative distribution of lyso-Gb3 and its analogues in plasma is similar from one individual to another in the same group of Fabry patients, irrespective of ERT. This study revealed a large discrepancy between the relative abundance of lyso-Gb3 and its analogues in urine and plasma. Further studies will thus be needed to better understand the metabolic relationship between plasma and urine lyso-Gb3-related biomarkers.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".