Exploring cardiac phenotypes of Drosophila orthologues of human genes associated to Brugada Syndrome (BrS)
Bibliographic record
Abstract
SUMMARY Brugada syndrome (BrS) is a rare cardiac arrhythmic disorder with high risk of sudden cardiac death. Recent advances have identified more than 20 risk loci with complex inheritance suggesting a polygenic model for BrS inheritance. These loci are in non-coding regions located in the vicinity of cardiac-expressed genes. This complex genetic architecture and the limited understanding of BrS genetic and molecular mechanisms hinder the development of efficient prevention strategies in the context of this syndrome and are unfavorable to the implementation of therapeutic interventions. In this context, understanding the functional impact of the identified putative risk alleles is a prerequisite. Here, we used the fly model to systematically test whether orthologues of genes located near risk alleles for BrS participate to cardiac function. The fly is the simplest model with a heart muscle and is a powerful genetic model suitable for efficient screening of candidate genes, providing a whole organism-based assessment of cardiac development, structure and function. Using high-speed heart imaging platform on intact flies, we invalided the cardiac expression of the fly orthologues of human genes associated to BrS and characterized whether they are cell autonomously implicated in heart functioning. Our results provide an overview of cardiac phenotypes associated with genes potentially involved in BrS, enabling their prioritization for further investigations in mammalian models.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".