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ADEPT, airway disease endotyping for personalized treatment: Interim analysis of asthma patients

2013· article· en· W1957190588 on OpenAlexaff
Matt Loza, Irina Strâmbu, Michel Laviolette, Dave Singh, J. Mark FitzGerald, Steven Kelsen, A. Eich, Andrea Ludwig-Sengpiel, Geoffrey Chupp, Celeste Porsbjerg, Patrick Berger, Richard Leigh, Joel N. Kline, Mark T. Dransfield, William J. Calhoun, Azra Hussaini, Pascal Chanez, Vedrana S. Susulic, Philip E. Silkoff, Frédéric Baribaud

Bibliographic record

VenueEuropean Respiratory Journal · 2013
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsUniversity of CalgaryUniversity of British ColumbiaUniversité Laval
Fundersnot available
KeywordsAsthmaMedicineInterim analysisCOPDSteroidAirwayImmunologyPeriostinCorticosteroidTranscriptomeInternal medicineGene expressionGeneBioinformaticsClinical trialAnesthesiaBiology

Abstract

fetched live from OpenAlex

Background ADEPT is a non-interventional study to characterize the clinical and molecular profiles of healthy, asthmatic, and COPD patients Methods Gene signatures of steroid up- and down- regulated genes were generated from in vitro stimulations of primary human airway cells from commercial sources. These steroid gene signatures were evaluated in the ADEPT asthma biopsies using GSEA to evaluate steroid responsiveness. Results The interim analysis included 15 healthy nonatopic subjects and 15, 13, and 11 mild, moderate, and severe asthmatics, respectively. The steroid down-regulated gene signature was enriched in moderate and severe but not mild asthma. The up-regulated signature was suppressed in mild asthma, and enriched in moderate but not severe asthma (Table 1). Asthma-related genes, including ALOX15, MUC5AC, and periostin, were each over-expressed in at least 2 asthma groups. Expression of B cell, T cell, mast cell genes was decreased in moderate and severe asthma. Steroid gene signature enrichment in asthma Signature Mild Moderate Severe Steroid, Down regulation 0.30 (-0.59) 0.015 (-0.76) <0.0001 (-0.93) Steroid, Up regulation 0.098 (-0.53) 0.0073 (0.78) 0.74 (-0.32) Nominal p-value (enrichment score), with healthy nonatopic control group as reference Conclusions Differential enrichment of the steroid gene signature was detected and corresponded to severity group. Confirmation of the unique findings in the severe asthma group awaits testing with the complete dataset. The unexpected findings in severe asthma may help elucidate mechanisms underlying steroid resistance.

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)0.002
metaresearch head score (Gemma)0.002
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 score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
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 head0.029
GPT teacher head0.290
Teacher spread0.261 · 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
Published2013
Admission routes1
Has abstractyes

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