Rejection-associated Mitochondrial Impairment After Heart Transplantation
Bibliographic record
Abstract
BACKGROUND: Mitochondrial dysfunction is associated with poor allograft prognosis. Mitochondrial-related gene expression (GE) in endomyocardial biopsies (EMBs) could be useful as a nonimmune functional marker of rejection. We hypothesize that acute cardiac allograft rejection is associated with decreased mitochondrial-related GE in EMBs. METHODS: We collected 64 routines or clinically indicated EMB from 47 patients after heart transplant. The EMBs were subjected to mRNA sequencing. We conducted weighted gene coexpression network analysis to construct module-derived eigengenes. The modules were assessed by gene ontology enrichment and hub gene analysis. Modules were correlated with the EMBs following the International Society of Heart and Lung Transplantation histology-based criteria and a classification based on GE alone; we also correlated with clinical parameters. RESULTS: The modules enriched with mitochondria-related and immune-response genes showed the strongest correlation to the clinical traits. Compared with the no-rejection samples, rejection samples had a decreased activity of mitochondrial-related genes and an increased activity of immune-response genes. Biologic processes and hub genes in the mitochondria-related modules were primarily involved with energy generation, substrate metabolism, and regulation of oxidative stress. Compared with International Society of Heart and Lung Transplantation criteria, GE-based classification had stronger correlation to the weighted gene coexpression network analysis-derived functional modules. The brain natriuretic peptide level, ImmuKnow, and Allomap scores had negative relationships with the expression of mitochondria-related modules and positive relationships with immune-response modules. CONCLUSIONS: During acute cardiac allograft rejection, there was a decreased activity of mitochondrial-related genes, related to an increased activity of immune-response genes, and depressed allograft function manifested by brain natriuretic peptide elevation. This suggests a rejection-associated mitochondrial impairment.
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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) | 0.000 | 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".