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Record W4386960066 · doi:10.1101/2023.09.19.558348

Within-host rates of insertion and deletion in the HIV-1 surface envelope glycoprotein

2023· preprint· en· W4386960066 on OpenAlexafffund
John Palmer, Vlad Novitsky, Roux-Cil Ferreira, Art F. Y. Poon

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsWestern University
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchOntario Genomics
KeywordsIndelBiologyINDEL MutationCoalescent theoryGeneticsGlycosylationPoisson distributionPhylogenetic treeEvolutionary biologyGeneComputational biologyMathematicsSingle-nucleotide polymorphismStatisticsGenotype

Abstract

fetched live from OpenAlex

Abstract Under selection by neutralizing antibodies, the HIV-1 envelope glycoprotein gp120 undergoes rapid evolution within hosts, particularly in regions encoding the five variable loops (V1-V5). Indel polymorphisms are abundant in these loops, where they can facilitate immune escape by modifying the length, composition and glycosylation profile of these structures. Here, we present a comparative analysis of within-host indel rates and characteristics within the variable regions of gp120. We analyzed a total of 3,437 HIV-1 gp120 sequences sampled longitudinally from 29 different individuals using coalescent models in BEAST. Next, we used Historian to reconstruct ancestral sequences from the resulting tree samples, and fit a Poisson generalized linear model to the distribution of indel events to estimate their rates in the five variable loops. Overall, the mean insertion and deletion rates were 1.6 × 10 − 3 and 2.5 × 10 − 3 / nt / year, respectively, with significant variation among loops. Insertions and deletions also followed similar length distributions, except for significantly longer indels in V1 and V4 and shorter indels in V5. Insertions in V1, V2, and V4 tended to create new N-linked glycosylation sites significantly more often than expected by chance, which is consistent with positive selection to alter glycosylation patterns.

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)0.003
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 score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0000.000
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 head0.024
GPT teacher head0.248
Teacher spread0.225 · 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
Published2023
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicHIV Research and Treatment→French-language works237,207→