Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic review
Bibliographic record
Abstract
BACKGROUND: Cyanotic congenital heart disease (CCHD) affects over 3 million individuals globally and can progress to heart failure. Mitochondrial dysfunction is well established in adult heart failure and is also a central feature of CCHD. CCHD cyanosis itself contributes to further mitochondrial dysfunction. Systems biology methods detail the epigenomic, transcriptomic, and metabolomic profile of biological samples. This systematic review highlights CCHD systems biology literature related to mitochondrial dysfunction. METHODS: OVID/Medline was searched between January 2010 and June 2025. Studies implementing untargeted systems biology methods in CCHD tissue or plasma were included. Genes with differential expression between CCHD and unaffected controls were pooled and analysed using GO term functional enrichment for pathway analysis, transcription factor and kinase enrichment, and metabolic pathways. FINDINGS: From 31 included studies (genomic: n = 5, epigenomic: n = 3, transcriptomic: n = 23, proteomic: n = 2, metabolomic: n = 3, lipidomic: n = 1), we identified 8 pathogenic/likely pathogenic single nucleotide polymorphisms, 73 differentially methylated genes, 4170 differentially expressed genes, 173 differentially expressed proteins between CCHD versus unaffected controls. Several genes involved in mitochondrial respiratory chain (NDUFV1, NDUFV2, NDUFA5, NDUFS3, COX5A, COQ7) were identified. INTERPRETATION: CCHD pathogenesis and progression are associated with mitochondrial dysfunction through changes in metabolism, fission, and fusion. FUNDING: Vanier CIHR Scholarship, UHN Research Studentship, and Ontario Graduate Scholarship. Translational Biology and Engineering Program seed operating funds and research funding from the Heart and Stroke Foundation of Canada.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 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) | 0.000 | 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 teacher head, 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".