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Record W4404874481 · doi:10.1038/s41467-024-54764-3

SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections

2024· article· en· W4404874481 on OpenAlexaff
Joshua Rosenheim, Rishi K Gupta, Clare Thakker, Tiffeney Mann, Lucy Bell, Claire Broderick, Kieran Madon, Loukas Papargyris, Pete Dayananda, Andrew Kwok, James Greenan-Barrett, Helen R. Wagstaffe, Emily Conibear, Joe Fenn, Seran Hakki, Rik G.H. Lindeboom, Lisa M. Dratva, Briac Lemetais, Caroline M. Weight, Cristina Venturini, Myrsini Kaforou, Michael Levin, Mariya Kalinova, Alex Mann, Andrew Catchpole, Julian C. Knight, Marko Nikolić, Sarah A. Teichmann, Ben Killingley, William Barclay, Benny Chain, Ajit Lalvani, Robert S. Heyderman, Christopher Chiu, Mahdad Noursadeghi

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicRespiratory viral infections research
Canadian institutionsInstitute of Infection and Immunity
FundersMedical Research CouncilNational Institute for Health and Care ResearchAction Medical ResearchWellcome TrustWellcome
KeywordsRhinovirusVirusGene expressionBiologyImmunologyInterferonVirologyRespiratory systemGene expression profilingReal-time polymerase chain reactionViral loadMedicineGeneGenetics

Abstract

fetched live from OpenAlex

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. Blood MX1 expression is superior to IFI27 expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore, MX1 expression offers potential to stratify patients for antiviral therapy or infection control interventions. Blood IFI27 expression is superior to MX1 expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

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 integrity0.0000.001
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 head0.136
GPT teacher head0.448
Teacher spread0.312 · 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

Citations11
Published2024
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicRespiratory viral infections researchFrench-language works237,207