eoPred: predicting the placental phenotype of early-onset preeclampsia using public DNA methylation data
Bibliographic record
Abstract
Background: A growing body of literature has reported molecular and histological changes in the human placenta in association with preeclampsia (PE). Placental DNA methylation (DNAme) and transcriptomic patterns have revealed molecular subgroups of PE that are associated with placental histopathology and clinical phenotypes of the disease. However, the clinical and molecular heterogeneity of PE both across and within subtypes complicates the study of this disease. PE is most strongly associated with placental pathology and adverse fetal and maternal outcomes when it develops early in pregnancy. We focused on placentae from pregnancies affected by preeclampsia that were delivered before 34 weeks of gestation to develop eoPred, a predictor of the DNAme signature associated with the placental phenotype of early-onset preeclampsia (EOPE). Results: Public data from 83 placental samples (HM450K), consisting of 42 EOPE and 41 normotensive preterm birth (nPTB) cases, was used to develop eoPred—a supervised model that relies on a highly discriminative 45 CpG DNAme signature of EOPE in the placenta. The performance of eoPred was assessed using cross-validation (AUC = 0.95) and tested in an independent validation cohort ( n = 49, AUC = 0.725). A subset of fetal growth restriction (FGR) and late-PE cases showed a similar DNAme profile at the 45 predictive CpGs, consistent with the overlap in placental pathology between these conditions. The relationship between the EOPE probability generated by eoPred and various phenotypic variables was also assessed, revealing that it is associated with gestational age, and it is not driven by cell composition differences. Conclusion: eoPred relies on a 45-CpG DNAme signature to predict a homogeneous placental phenotype of EOPE in a discrete or continuous manner. Using this classifier should 1) aid in the study of placental insufficiency and improve the consistency of future placental DNAme studies of PE, 2) facilitate identifying the placental phenotype of EOPE in public data sets and 3) importantly, standardize the placental diagnosis of EOPE to allow better cross-cohort comparisons. Lastly, classification of cases with eoPred will be useful for investigating the relationship between placental pathology and genetic or environmental variables.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".