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Record W3047365219 · doi:10.1038/s41467-020-17673-9

An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

2020· article· en· W3047365219 on OpenAlexafffund
Lang Wu, Yaohua Yang, Xingyi Guo, Xiao‐Ou Shu, Qiuyin Cai, Xiang Shu, Bingshan Li, Ran Tao, Chong Wu, Jason B. Nikas, Yanfa Sun, Jingjing Zhu, Monique J. Roobol, Graham G. Giles, Hermann Brenner, Esther M. John, Judith A. Clements, Eli Marie Grindedal, Jong Y. Park, Janet L. Stanford, Zsofia Kote‐Jarai, Christopher A. Haiman, Rosalind A. Eeles, Wei Zheng, Jirong Long, Brian E. Henderson, Fredrick R. Schumacher, Douglas F. Easton, Sara Benlloch, Ali Amin Al Olama, Kenneth Muir, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, Susan M. Gapstur, Victoria L. Stevens, Catherine M. Tangen, Jyotsna Batra, Henrik Grönberg, Nora Pashayan, Johanna Schleutker, Demetrius Albanes, Stephanie J. Weinstein, Alicja Wolk, Catharine West, Lorelei A. Mucci, Géraldine Cancel‐Tassin, Stella Koutros, Karina D. Sørensen, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Cezary Cybulski, Børge G. Nordestgaard, Christiane Maier, Jeri Kim, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Hassan Abdul Razack, Lisa F. Newcomb, Marija Gamulin, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago Dominguez, F. Ménégaux, Kay‐Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau, David J. Hunter, William J. Blot, Elio Ríboli

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsUniversity of AlbertaPrincess Margaret Cancer Centre
FundersNational Cancer InstituteCancer Council VictoriaMedical Research CouncilCanadian Institutes of Health ResearchSchool of Medicine, Vanderbilt UniversityCancer Research InstituteRoyal Marsden NHS Foundation TrustProstate Cancer Foundation of AustraliaNational Institute for Health and Care ResearchEuropean CommissionBreast Cancer Research FoundationNational Institutes of HealthOvarian Cancer Research FundNational Health and Medical Research CouncilCancer Research UKProstate Cancer FoundationNational Cancer Research InstituteVanderbilt University
KeywordsDNA methylationProstate cancerOmicsComputational biologyBioinformaticsBiomarker discoveryBiomarkerMedicineCancerBiologyProteomicsInternal medicineGeneticsGeneGene expression

Abstract

fetched live from OpenAlex

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.

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 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)0.000
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 score0.408
Threshold uncertainty score0.669

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.016
GPT teacher head0.367
Teacher spread0.351 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations246
Published2020
Admission routes2
Has abstractyes

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