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Record W4362673659 · doi:10.1038/s43587-023-00391-4

Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes

2023· article· en· W4362673659 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueNature Aging · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsnot available
FundersInstitute of GeneticsLeibniz-GemeinschaftMedical Research CouncilChief Scientist Office, Scottish Government Health and Social Care DirectorateLudwig-Maximilians-Universität MünchenSchool of Informatics, University of EdinburghAlzheimer’s Research UKHelmholtz Zentrum MünchenBundesministerium für Bildung und ForschungUniversity of EdinburghWellcome TrustAlzheimer's SocietyNational Alliance for Research on Schizophrenia and DepressionUK Research and InnovationAlan Turing InstituteDeutsches Zentrum für Herz-KreislaufforschungHelsingin YliopistoRoyal College of Physicians of EdinburghScottish Funding CouncilScottish GovernmentAlzheimer’s SocietyWellcome
KeywordsReceiver operating characteristicType 2 diabetesMedicineFramingham Risk ScoreDNA methylationCohortArea under the curveStatisticsOncologyInternal medicineAlgorithmMachine learningDiabetes mellitusComputer scienceMathematicsDiseaseBiologyGeneticsEndocrinology

Abstract

fetched live from OpenAlex

Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D incidence risk. Previous studies have been largely constrained by linear assumptions, the use of cytosine–guanine pairs one-at-a-time and binary outcomes. We present a flexible approach (via an R package, MethylPipeR) based on a range of linear and tree-ensemble models that incorporate time-to-event data for prediction. Using the Generation Scotland cohort (training set ncases = 374, ncontrols = 9,461; test set ncases = 252, ncontrols = 4,526) our best-performing model (area under the receiver operating characteristic curve (AUC) = 0.872, area under the precision-recall curve (PRAUC) = 0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC = 0.839, precision–recall AUC = 0.227). Replication was observed in the German-based KORA study (n = 1,451, ncases = 142, P = 1.6 × 10−5). Early type 2 diabetes (T2D) risk assessment could help slow or prevent disease onset. Here the authors used blood-based DNA methylation data to develop 10-year risk prediction models for incident T2D. The results show an improvement in performance beyond standard risk factors typically used to predict the risk of T2D onset.

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.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.239

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.010
GPT teacher head0.265
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it