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Record W4406404907 · doi:10.1038/s41467-025-56054-y

Causality-driven candidate identification for reliable DNA methylation biomarker discovery

2025· article· en· W4406404907 on OpenAlexfundno aff
Xinlu Tang, Rui Guo, Zhanfeng Mo, Wenli Fu, Xiaohua Qian

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene expression and cancer classification
Canadian institutionsnot available
FundersNational Institute on AgingNational Institutes of HealthH. Lundbeck A/SServierNational Natural Science Foundation of ChinaEisaiGenentechIXICONorthern California Institute for Research and EducationPfizerBiogenBioClinicaCanadian Institutes of Health ResearchNatural Science Foundation of ShanghaiF. Hoffmann-La RocheUniversity of Southern CaliforniaShanghai Municipal Education CommissionU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationAlzheimer's Association
KeywordsBiomarker discoveryComputational biologyDNA methylationIdentification (biology)BiomarkerCausality (physics)BiologyGeneticsComputer scienceBioinformaticsGeneProteomicsGene expression

Abstract

fetched live from OpenAlex

Despite vast data support in DNA methylation (DNAm) biomarker discovery to facilitate health-care research, this field faces huge resource barriers due to preliminary unreliable candidates and the consequent compensations using expensive experiments. The underlying challenges lie in the confounding factors, especially measurement noise and individual characteristics. To achieve reliable identification of a candidate pool for DNAm biomarker discovery, we propose a Causality-driven Deep Regularization framework to reinforce correlations that are suggestive of causality with disease. It integrates causal thinking, deep learning, and biological priors to handle non-causal confounding factors, through a contrastive scheme and a spatial-relation regularization that reduces interferences from individual characteristics and noises, respectively. The comprehensive reliability of the proposed method was verified by simulations and applications involving various human diseases, sample origins, and sequencing technologies, highlighting its universal biomedical significance. Overall, this study offers a causal-deep-learning-based perspective with a compatible tool to identify reliable DNAm biomarker candidates, promoting resource-efficient biomarker discovery.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.007
metaresearch head score (Gemma)0.019
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.007
Threshold uncertainty score0.038

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.019
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.002
Open science0.0020.003
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.021
GPT teacher head0.347
Teacher spread0.325 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations6
Published2025
Admission routes1
Has abstractyes

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