Study of Genome-Wide DNA Methylation Profile in a Large Cohort of Patients with 22q11.2 Deletion Syndrome
Bibliographic record
Abstract
22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome in humans. The clinical phenotype is variable among different patients, also when they come from the same family, suggesting that nongenetic factors may be implicated in the pathogenesis. Recently, a specific episignature was defined for patients affected with 22q11.2DS. However, it has not been yet clarified whether these changes may reflect the variability of the phenotype observed among different patients. The study is aimed at defining genome-wide DNA methylation profiling in a large cohort of patients, including 63 carrying a deletion on the 22q11.2 chromosome and 5 with clinical features of DGS in whom genetic analysis did not reveal any alteration on the chromosome 22 (DGS-like). Among patients with 22q11.2 deletion, 12 were identified through FISH, suggesting that the deletion includes the proximal region, but information on the extension of the deletion is not available. For the remaining 51 patients, 38 carried the typical A-D deletion, 3 carried an A-B deletion, 7 carried a C-D deletion, while 3 patients carried a deletion downstream the DGS region. The analysis included 20 familial cases from 8 kindred. By selecting the 160 previously published differentially methylated CpG probes (DMPs), we were able to distinguish a specific methylation profile in the group of 38 patients carrying the typical A-D deletion, in the 3 patients carrying the A-B deletion, and in those diagnosed with FISH. On the contrary, the 7 patients carrying the distal C-D deletion, the 3 patients carrying a deletion downstream the DGS region and the DGS-like clustered with the controls. When the analysis was extended to a larger number of DMPs, we observed a gradient among typical deletion, distal deletions, DGS-like, and controls. Interestingly, most of the DMPs were found in the DGS region on the non-deleted allele. Hierarchical clustering also revealed similarities among affected and unaffected members of the different families, suggesting that epigenetic modifications may be partially inherited. These data showed a gradient of DMPs among typical deletion, distal deletions, DGS-like, and controls. This may suggest a correlation between the severity of the clinical phenotype and the degree of DNA methylation.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".