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Record W4205202542 · doi:10.1038/s41467-021-27881-6

Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2

2022· article· en· W4205202542 on OpenAlexfundno aff
Kapil Gupta, Christine Toelzer, Maia Kavanagh Williamson, Deborah K. Shoemark, A. Sofia F. Oliveira, David A. Matthews, Abdulaziz Almuqrin, Oskar Staufer, Sathish K.N. Yadav, Ufuk Borucu, Frédéric Garzoni, Daniel J. Fitzgerald, Joachim P. Spatz, Adrian J. Mulholland, Andrew D. Davidson, Christiane Schaffitzel, Imre Berger

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilMedical Research CouncilHamilton Health Sciences FoundationBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftUniversity of BristolElizabeth Blackwell Institute for Health Research, University of BristolWeizmann Institute of ScienceWellcomeImperial College LondonResearch Councils UKBritish Society for Antimicrobial ChemotherapyU.S. Food and Drug AdministrationMax-Planck-GesellschaftEngineering and Physical Sciences Research CouncilHeidelberg Biosciences International Graduate SchoolUK Research and InnovationWellcome Trust
KeywordsViral quasispeciesBiologyTropismFurinInfectivityGeneticsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Tissue tropismCell typeViral entryCoronavirusVirologyEvolutionary biologyComputational biologyCoronavirus disease 2019 (COVID-19)CellGeneVirusViral replicationGenome

Abstract

fetched live from OpenAlex

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.

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 score0.001
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)0.0010.000

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 head0.047
GPT teacher head0.338
Teacher spread0.291 · 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
Published2022
Admission routes1
Has abstractyes

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