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Using Viral Dynamics to Connect Clinical Markers of Disease Progression to Sequence Evolution during HIV Infection

2014· article· en· W2273757900 on OpenAlexaff
Andrew E. Adams, Zabrina L. Brumme, Alexander R. Rutherford, Ralf W. Wittenberg

Bibliographic record

VenueAIDS Research and Human Retroviruses · 2014
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsSimon Fraser University
Fundersnot available
KeywordsViral loadBiologyHuman immunodeficiency virus (HIV)VirologyViral evolutionViral infectionImmune escapeImmune systemEvolutionary biologyGeneticsVirusGeneRNA

Abstract

fetched live from OpenAlex

HIV-1 remains a global health challenge, with over 35 million people infected. The high rates of turnover and evolutionary adaptability exhibited by HIV-1 pose a particular challenge to HIV-1 vaccine development. We developed a dynamic model of HIV-1 infection that uses equilibration, adaptation, and inheritance to model the initial infection and successive generations of viral lineages. The model allows viruses to generate new lineages in proportion to their viral load. These lineages compete for immune cells to infect. We use this model to demonstrate how viruses with a sufficiently high mutation rate could overcome the immune system, even when most changes are expected to be detrimental to viral fitness. We have calibrated our model to match averages of CD4+ T cells/mm^3 and HIV-1 RNA/ml derived from 91 HIV-infected individuals studied longitudinally during various disease stages. We also explore the use of phylogenies to validate the underlying composition of viral load.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.077
Threshold uncertainty score0.487

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.098
GPT teacher head0.437
Teacher spread0.340 · 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 teacher head, 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

Citations1
Published2014
Admission routes1
Has abstractyes

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