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Record W3130477062 · doi:10.1038/s41598-021-84070-7

The influence of human genetic variation on Epstein–Barr virus sequence diversity

2021· article· en· W3130477062 on OpenAlexaff
Sina Rüeger, Christian Hammer, Alexis Loetscher, Paul J. McLaren, Dylan Lawless, Olivier Naret, Nina Khanna, Enos Bernasconi, Matthias Cavassini, Huldrych F. Günthard, Christian R. Kahlert, Andri Rauch, Daniel P. Depledge, Sofia Morfopoulou, Judith Breuer, Evgeny M. Zdobnov, Jacques Fellay, Karoline Aebi‐Popp, A Anagnostopoulos, Manuel Battegay, Jürg Böni, Dominique L. Braun, Heiner C. Bucher, Alexandra Calmy, Angela Ciuffi, G Dollenmaier, Matthias Egger, Luigia Elzi, Jan Fehr, Hansjakob Furrer, Christoph A. Fux, David Haerry, Barbara Hasse, Hans H. Hirsch, Matthias Hoffmann, Irène Hösli, Michael Huber, Laurent Kaiser, Olivia Keiser, Thomas Klimkait, Lisa Kottanattu, Roger D. Kouyos, Helen Kovari, Bruno Ledergerber, G Martinetti, Begoña Martínez de Tejada, Catia Marzolini, Karin J. Metzner, N Müller, Dunja Nicca, P Paioni, Giuseppe Pantaleo, Matthieu Perreau, Christoph Rudin, Alexandra Scherrer, Patrick Schmid, Roberto F. Speck, M Stöckle, Philip Tarr, Alexandra Trkola, Pietro Vernazza, Noémie Wagner, Gilles Wandeler, Rainer Weber, Sabine Yerly

Bibliographic record

VenueScientific Reports · 2021
Typearticle
Languageen
FieldMedicine
TopicViral-associated cancers and disorders
Canadian institutionsUniversity of ManitobaPublic Health Agency of Canada
FundersSwiss HIV Cohort Research FoundationFondation LeenaardsWellcome TrustSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Science Foundation
KeywordsBiologyGenetic variationVirusViremiaEpstein–Barr virusGeneticsHuman genetic variationGenomeVirologyPopulationGeneViral evolutionWhole genome sequencingHuman genomeMedicine

Abstract

fetched live from OpenAlex

Abstract Epstein–Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count < 200/mm 3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.

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)0.002
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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
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)0.0020.000

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 head0.021
GPT teacher head0.273
Teacher spread0.252 · 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

Citations17
Published2021
Admission routes1
Has abstractyes

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Same venueScientific ReportsSame topicViral-associated cancers and disordersFrench-language works237,207