The B-lymphoblastoid model in Barth syndrome
Bibliographic record
Abstract
Barth Syndrome (BTHS) is an ultra-rare, X-linked mitochondrial disorder caused by a variety of different mutations in the cardiolipin remodeling gene TAFAZZIN that results in cardiac and skeletal myopathy, as well as immunological deficits. Epstein-Barr virus-mediated transformation of B-lymphocytes has been used to generate B-lymphoblastoid cells that retain many of the characteristics of the initial cell line, but can be propagated extensively in culture to generate biological materials enabling study of the basic, natural function of this enzyme in cells, as well as disease-relevant effects and interventions. Notably, these model lines from individual donors are of particular value for understanding a disease with variable penetrance such as BTHS, where variation in genetic background can alter symptom severity considerably, even among closely-related individuals with the same mutation. Here, we review the generation, benefits, and limitations of the B-lymphoblastoid cell model in BTHS research, and provide an overview of recent advances in understanding the role of TAFAZZIN in mitochondrial biology from this model. Implications of these findings for understanding the pathology of BTHS, and determining future directions, are also provided, along with a review of recent advances in our understanding of the mechanism of TAFAZZIN function in cardiolipin degradation, remodeling and stability. • BTHS B-lymphoblastoid cells retain patient-specific TAFAZZIN mutations, making it an effective model to study how genetic variability affects BTHS disease severity. • Prevailing theories generated using BTHS B-lymphoblastoids suggested that the stability of cardiolipin critically depends on its interactions with inner mitochondrial membrane proteins. • BTHS B-lymphoblastoid cells are characterized by impaired cristae organization, enlarged mitochondria, decreased ETC stability/function, and dysregulated mitochondrial ion transport.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".