The liver proteome of individuals with a natural UGT2B17 complete deficiency
Bibliographic record
Abstract
Glucuronidation is a crucial pathway for the metabolism and detoxification of drugs and endobiotics, and primarily occurs in the liver. UGT2B17 is one of the 22 glycosyltransferases (UGT) that catalyze this reaction. In a large proportion of the population, UGT2B17 is absent due to complete gene deletion. We hypothesized that a UGT2B17 human deficiency affects the composition and function of the liver proteome, potentially provoking compensatory responses, and altering interconnected pathways and regulatory networks. The objective was to elucidate the liver proteome of UGT2B17-deficient individuals. Liver specimens from UGT2B17-deficient and proficient individuals were compared by mass spectrometry-based proteomics using data-independent acquisition. In UGT2B17-deficient livers, 80% of altered proteins showed increased abundance with a notable enrichment in various metabolic and chemical defense pathways, cellular stress and immune-related responses. Enzymes involved in the homeostasis of steroids, nicotinamide, carbohydrate and energy metabolism, and sugar pathways were also more abundant. Some of these changes support compensatory mechanisms, but do not involve other UGTs. An increased abundance of non-metabolic proteins suggests an adaptation to endoplasmic reticulum stress, and activation of immune responses. Data implies a disrupted hepatocellular homeostasis in UGT2B17-deficient individuals and offers new perspectives on functions and phenotypes associated with a complete UGT2B17 deficiency.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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 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".