Understanding the development of variable craniofacial phenotypes caused by altered methylation affecting Wnt9b in A‐strain mice
Bibliographic record
Abstract
Variable clinical presentation is common in many structural birth defects, two children with the same genetic mutation often have different clinical presentation. Therefore, understanding the developmental origin of such variability is of fundamental importance to developing patient targeted treatment, or precision medicine. A/WySn mice are genetically identical, inbred mice, but about 20% of them develop cleft lip and palate. This has been linked to loss of methylation at an IAP retrotransposon near Wnt9b (Wnt9bIAP). Using a newly developed protocol for generating RNA and DNA as well as a 3D microCT scan that can be used to quantify shape, we show that loss of methylation at this locus directly correlates with facial shape in precleft embryos. Line1 methylation is unaffected in embryos with abnormal Wnt9bIAP methylation levels. Wnt9bIAP methylation levels are bimodal, but continuous, as are facial shape, Wnt9b and Axin2 levels. We use all of these factors to build a model of how multiple continuous bimodal inputs lead to a discontinuous phenotype (clefting). We also determine how this model relates to underlying changes in the cell biology in the affected tissue. Support or Funding Information NIH R01 2R01DE019638 to RSM and BH. NSERC 238992‐17 to BH. Alberta Children's Hospital Research Institute Fellowship to RG. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".