Abstract 656: Construction and Application of an Epigenetic Atlas of the Human Heart
Bibliographic record
Abstract
Epigenetic modifications, including DNA methylation, regulate gene expression and contribute to the differentiation of cells. Tissues are characterized by methylation patterns that reflect their specific functions and origin. Currently, there is limited knowledge of the epigenetic patterns of the heart. To address this gap, we generated methylation profiles for all anatomical regions of the human heart. We hypothesize that unique differentially methylated regions (DMRs) of DNA exist for each cardiac region and that these patterns are disrupted in heart failure. Using non-diseased cardiac tissue and reduced representation bisulfite sequencing on a Illumina platform, we generated genome-wide methylomes for the human right atrium (n=4), left atrium (n=4), right ventricle (n=4), left ventricle (n=4), aorta (n=3), pulmonary artery (n=2), mitral valve (n=3), tricuspid valve (n=3), aortic valve (n=3) and pulmonary valve (n=3). DMRs, defined as regions with significantly different mean methylation differences, were identified using Metilene. For each tissue we identified between 10-20 million reads covering 8-10 million CpG methylation sites and 4-228 tissue-specific DMRs. There were relatively few (4) different DMRs between the left and right ventricles but 228 unique DMRs were found in the vessels (aorta and pulmonary artery) compared to the ventricles including regions upstream of BMP3 and FOXC1 , genes implicated in cardiogenesis. We then applied this approach and normal data to the analysis of disease. We generated additional left ventricular methylomes from adult (n=3) and pediatric (n=3) patients with heart failure. We identified 19 unique DMRs in the adult group and 107 in the pediatric group. Genes associated with pediatric HF DMRs included ROCK1 and FBLN2 that have been previously implicated in contraction and remodelling. We have created an atlas of the human heart based upon differences in DNA methylation between the anatomical regions of the human heart. This data will help increase our understanding of cardiac development, identify new disease biomarkers and have application to a wide range of cardiac diseases
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.003 |
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".