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CpG methylation in the TGFB1 and IL-6 gene promoters serve as surrogate biomarkers for diagnosis of IBD in children

2020· article· en· W4313373266 on OpenAlexaffabout
Ali Ahmad, Suzanne Samarani, Claire-Lucas Dupont, Valérie Marcel, David R. Mack, Ernest G. Seidman, Colette Deslandres, Prévost Jantchou, Devendra Amre

Bibliographic record

VenueThe Journal of Immunology · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsMcGill UniversityCentre Hospitalier Universitaire Sainte-Justine
Fundersnot available
KeywordsCpG siteMethylationMedicineLogistic regressionDNA methylationInflammatory bowel diseasePromoterUlcerative colitisArea under the curveImmunologyReceiver operating characteristicGeneDiseaseInternal medicineBiologyGeneticsGene expression

Abstract

fetched live from OpenAlex

Abstract Crohn’s disease (CD) and ulcerative colitis (UC) are recurrent, chronic forms of inflammatory bowel diseases (IBD), the diagnosis of which can entail long delays. The delays can lead to disease presentation with complications and high morbidity. Therefore, better diagnostic markers for IBD are required. We investigated whether methylation marks in the TGFB1 and IL-6 gene promoters could be of diagnostic utility in IBD. To this end, we conducted a case-control study using peripheral blood DNA samples from 67 CD and 37 UC pediatric patients, and from 43 age-matched healthy controls. The patients were recruited from three pediatric gastroenterology clinics across Canada. The DNA samples were processed to identify methylation sites (CpG) across the promoter regions of the TGFB1 and IL-6 genes using the Sequenom technology. After implementing quality control measures, and initial non-parametric univariate (Man-Whitney U test) analyses, multivariate logistic regression analyses was carried out to identify models with the best fit (Akaike Information Criteria) and the greatest discriminatory capabilities (Area Under the Receiver Operating Curve). Logistic regression analysis showed that a model comprising 14 TGFB1 CpG sites had high discriminatory ability to separate CD from controls (AUC=0.94). Similarly, a logistic model comprising 9 CpG sites in the TGFB1 gene had near perfect ability to discriminate between UC and controls (AUC=0.99). A logistic model comprising three CpG sites in the TGFB1 gene had moderate ability (AUC=0.81) to discriminate between CD and UC. In conclusion, CpG methylation in the TGFB1 gene promoter has high discriminative power for identifying CD and UC, and could serve as an important diagnostic markers.

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)0.001
metaresearch head score (Gemma)0.004
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.009
GPT teacher head0.238
Teacher spread0.228 · 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

Citations0
Published2020
Admission routes2
Has abstractyes

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