Cluster Analysis Identifies Phosphatidylcholine Species in the Liver and Heart as Prediction Hubs in Ossabaw Swine with Cardio‐Metabolic Heart Failure
Bibliographic record
Abstract
We recently developed an Ossabaw swine model (Western Diet and aortic banding; WD‐AB) that exhibits features consistent with cardio‐metabolic heart failure (HF). This pre‐clinical model has a pattern of findings possibly useful for enhancing our understanding of the interactions between metabolic syndrome and HF. The aim of this study is to use advanced quantitative methods to reveal novel relationships and candidate predictors we hypothesize may be important to cardio‐metabolic HF. A large‐scale data repository was created containing 142 hemodynamic, structural, and functional cardiovascular measures, 413 lipid species identified using shotgun lipidomics, and 28,386 mRNA‐transcripts revealed by RNA‐seq. Repository data was generated from heart, vascular, hepatic, and blood samples collected from 2 groups of intact female Ossabaw swine: 1) lean control (CON; N=5); and 2) WD‐AB (N=4). Logistic regression models with AUC scores identified a subset of measurements predictive of HF status that included 1,237 measurements (4.3%). Log2 fold changes were then calculated and statistically significant changes (p<0.05) with absolute value log2 fold changes >1 were considered. Pearson correlations for these 153 measurements were analyzed to identify redundant information using k‐medoids clustering analysis with an average silhouette approach. Twenty‐eight left ventricle (LV) genes and 125 lipids in 2 clusters (Fig. 1 Circos plot) with center points were identified. Cluster 1 (7 mRNA‐transcripts, 70 lipids) was composed of strong correlations with center point phosphatidylcholine (PC) alkyl ether (a) species 32 from the liver (LIVER_PC_32.0a_754) that increased 10‐fold in the WD‐AB group (P<0.05; 25±4 CON vs. 277±56 WD‐AB pmols/mg). Cluster 2 (21 mRNA‐transcripts, 55 lipids) had center point PC species 38.4a from the LV (HEART_PC_38.4a_830) that increased ~3‐fold in the WD‐AB group (P<0.05; 37±3 CON vs. 102±3 WD‐AB pmols/mg). Identified PCa species containing arachidonic acid are storage depots for bioactive oxylipids (eicosanoids) and a precursor for platelet activating factor production. Increased alkyl ether phospholipids may also indicate increased peroxisome proliferation (the site of alkyl ether biosynthesis) and the potential to increase unknown peroxisome proliferator‐activated receptor (PPAR) endogenous ligands. In conclusion, PCa species identified from the heart and liver of WD‐AB animals may be underappreciated and have predictive significance for cardio‐metabolic HF. Ongoing work includes enrichment analysis to determine biological processes underlying clusters.
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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) | 0.000 | 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 | 0.000 | 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".