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Record W4390697935 · doi:10.1101/2024.01.03.24300792

Gene dysregulation among virally suppressed people living with HIV links to non-AIDS defining cancer pathways

2024· preprint· en· W4390697935 on OpenAlexaff
Bryan C. Quach, Eric J. Earley, Linran Zhou, Caryn Willis, Jesse A. Marks, Jeran K. Stratford, Fang Fang, Laura J. Bierut, M-J S Milloy, Kanna Hayashi, Kora DeBeck, Dana B. Hancock, Ke Xu, Bradley E. Aouizerat, Eric O. Johnson

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldMedicine
TopicViral-associated cancers and disorders
Canadian institutionsSimon Fraser UniversityBritish Columbia Centre on Substance UseUniversity of British Columbia
FundersNational Institutes of Health
KeywordsImmune dysregulationImmune systemTranscriptomeBiologyGeneQuantitative trait locusGenome-wide association studyExpression quantitative trait lociCancerDiseaseHeritabilityImmunologyGeneticsGene expressionMedicineSingle-nucleotide polymorphismGenotypeInternal medicine

Abstract

fetched live from OpenAlex

Abstract Combination antiretroviral therapy (ART) has changed the landscape of the HIV epidemic by providing an effective means for viral suppression to people living with HIV (PLWH). Understanding living with HIV as a chronic disease requires an improved understanding of how HIV and/or ART impacts susceptibility to and development of co-occurring conditions. Genome-wide gene expression (transcriptome) differences provide a key view into biological dysregulation associated with living with HIV. Here we present the first whole blood transcriptome-wide study comparing gene expression profiles between virally suppressed PLWH and HIV negative individuals (N=555). We identify 566 genes and 5 immune cell types with differential proportions by HIV status, which were significantly enriched for immune function and cancer pathways. Leveraging quantitative trait loci (QTL) for these HIV status-associated genes, partitioned heritability, and colocalization analyses, we observed limited genetic drivers of these relationships. Our findings suggest that gene dysregulation does not return to a pre-infection state for virally suppressed PLWH, and that persistent gene dysregulation is broadly associated with immune function and cancer pathways, highlighting potential biological drivers for these causes of excess mortality and targets for pharmacological preventative treatment among 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)0.000
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 score0.003
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0030.000

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 head0.011
GPT teacher head0.248
Teacher spread0.237 · 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
Published2024
Admission routes1
Has abstractyes

Explore more

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