Abstract 12334: A Flavor of Metabolic Disease in Pulmonary Hypertension
Bibliographic record
Abstract
Introduction: Pulmonary arterial hypertension (PAH) is a severe occlusive vascular disease of the lungs. One of the primary origin of PAH is pulmonary endothelial dysfunction driving vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Interestingly, endothelial dysfunction is maintained in culture, out of fluid and hemodynamic stress, humoral/hormonal, and inflammatory environment. Hypothesis: This aberrant phenotype may be imprinted in pulmonary endothelial cells (PEC) DNA though a specific pattern of DNA methylations. Methods: Genomic DNA was extracted from cultured PEC (passage 3): idiopathic PAH (n=11), heritable PAH (BMPR2 mutation carriers, n=10), controls (n=18). DNA methylation was assessed at over 485 000 CpG sites using the Illumina Infinium HumanMethylation450 Bead Chip. We normalized all arrays against each other using functional normalization. Differentially methylated sites were clustered with Cluster3.0 and heatmap were obtained with Treeview. Results: We discriminated controls vs PAH into 2 clusters of hypermethylated loci (119 probes= 31 promoters) and hypomethylated loci (331 probes= 116 promoters). Interestingly, 46 promoters/147 (clusters 1+2) (31%) were related to metabolic diseases (Ingenuity pathway analysis), and top molecules (fold changes up- and down regulated) includes molecules highly involved in cellular lipid metabolic process (ABCA1, Q=0.002 and ABCB4, Q=0.003), regulation of glucogenesis (ACN9, Q=2.78.10-5), lipid and glucose metabolism (ADIPOQ, Q=10-4), and insulin sensitivity and metabolism of glucose and lipids (miR-26a, Q=0.005), among others. Conclusions: the methylation fingerprint of PAH highlighted a set of molecules involved in metabolic disease and metabolism regulation. This may have fundamental and clinical implications in PAH.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.042 | 0.008 |
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".