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Record W3115701144 · doi:10.1136/thoraxjnl-2020-215866

DNA methylation is associated with airflow obstruction in patients living with HIV

2020· article· en· W3115701144 on OpenAlexafffund
Ana I. Hernández Cordero, Chen Xi Yang, Ma’en Obeidat, Julia Yang, Julie L. MacIsaac, Lisa M. McEwen, David Lin, Michael S. Kobor, Richard M. Novak, Fleur Hudson, Hartwig Klinker, Nila J. Dharan, SF Paul Man, Don D. Sin, Ken M. Kunisaki, Janice M. Leung

Bibliographic record

VenueThorax · 2020
Typearticle
Languageen
FieldMedicine
TopicPneumocystis jirovecii pneumonia detection and treatment
Canadian institutionsUniversity of British Columbia
FundersInstitute of Circulatory and Respiratory HealthNational Institute of Allergy and Infectious DiseasesWestern Canada Research GridNational Heart, Lung, and Blood InstituteCompute Canada
KeywordsMedicineDNA methylationMethylationEpigeneticsCOPDInternal medicineLung cancerAgeingCardiologyGeneticsDNABiologyGene

Abstract

fetched live from OpenAlex

Introduction People living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH. Methods Using blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV 1 , FEV 1 /FVC ratio and FEV 1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing. Results Airflow obstruction as defined by a FEV 1 /FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV 1 /FVC 1 and FEV 1 /FVC, respectively. No positions were associated with FEV 1 decline. Conclusion A large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.014
GPT teacher head0.229
Teacher spread0.216 · 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

Citations41
Published2020
Admission routes2
Has abstractyes

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