Abstract 13792: Integration of Proteomic and Transcriptomic Signatures in the Failing Right Ventricle of Rats With Monocrotaline Induced Pulmonary Arterial Hypertension
Bibliographic record
Abstract
Pulmonary arterial hypertension (PAH) is a chronic disease characterized by cellular remodeling in the pulmonary circulation. Pulmonary vascular obstruction, stiffening and constriction elevate pulmonary artery pressure and right ventricular (RV) afterload leading to failure (RVF). In a model of PAH induced by injection of monocrotaline (MCT, 60mg/kg sc) RV decompensation was confirmed. Then the RV proteome was analyzed using Mass Spectrometry (LC-MSMS). Proteomics revealed 1,277 differentially regulated proteins. Integration of this proteome with our previously published transcriptomic study of RVs harvested from an independent group of rats with MCT-induced PAH revealed 410 common targets, 15 of which were both highly enriched at protein (corrected q -values <0.05) and mRNA level (corrected p-adjust <0.05 ). Most regulated pairs were increased in RVF, including: Atrial natriuretic peptide protein (7.55-fold, transcript = 4.19-fold), Thrombospondin-4 protein (5.56-fold, transcript = 4.4-fold), Periostin (protein = 3.83-fold, transcript = 4.56-fold), Latent transforming growth factor beta binding protein 2 (2.67-fold, transcript = 4.16-fold), Heme oxygenase 1 (4.59-fold, transcript = 2.05-fold), Transforming Growth Factor Beta-1-Induced Transcript 4 Protein (3.82-fold, transcript = 2.1-fold), Transmembrane glycoprotein NMB (3.21-fold, transcript = 2.35-fold), S100 calcium-binding protein A4 (2.43-fold, transcript = 1.93-fold), Collagen XVIII, alpha 1 (2.59-fold, transcript = 1.61-fold), Ankyrin repeat domain 2 (4.04-fold, transcript = 2.49-fold), Procollagen-Lysine 2-Oxoglutarate 5-Dioxygenase 1, (6.89-fold, transcript = 2.3-fold), Tenascin-C (5.18-fold, transcript = 2.53-fold). In contrast, ATPase Na+/K+ Transporting Subunit Alpha 2 3.47 (protein = 3.47-fold, transcript = 2.23-fold) and Glutathione S-Transferase Zeta 1 (protein = 1.97-fold, transcript = 2.38-fold) were downregulated in RVF. A functional analysis of this list of regulated protein/transcript pairs revealed enriched functions include mitochondrial metabolism, cellular respiration and purine metabolism. Our integrated multiomic approach is validated by independent datasets and provides a molecular context for RVF in MCT-induced 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".