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Record W2810995872 · doi:10.1093/molbev/msy131

Evolution on the Biophysical Fitness Landscape of an RNA Virus

2018· article· en· W2810995872 on OpenAlexaff
Assaf Rotem, Adrian W.R. Serohijos, Connie B. Chang, Joshua T. Wolfe, Audrey Fischer, Thomas Mehoke, Huidan Zhang, Ye Tao, W. Lloyd Ung, Jeong‐Mo Choi, João V. Rodrigues, Abimbola O. Kolawole, Stephan A. Koehler, Susan K. Wu, Peter Thielen, Naiwen Cui, Plamen A. Demirev, Nicholas S. Giacobbi, Timothy R. Julian, Kellogg J. Schwab, Jeffrey S. Lin, Thomas J. Smith, James M. Pipas, Christiane E. Wobus, Andrew B. Feldman, David A. Weitz, Eugene I. Shakhnovich

Bibliographic record

VenueMolecular Biology and Evolution · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEvolution and Genetic Dynamics
Canadian institutionsUniversité de Montréal
FundersMaterials Research Science and Engineering Center, Harvard UniversityNational Institute of General Medical SciencesNational Natural Science Foundation of ChinaNational Institutes of HealthNational Science Foundation
KeywordsFitness landscapeBiologyEpistasisViral evolutionCapsidEvolutionary biologyEvolutionary dynamicsPopulationMolecular evolutionGenetic FitnessFolding (DSP implementation)Selection (genetic algorithm)Experimental evolutionViral entryRNAVirusComputational biologyGeneticsViral replicationBiological evolutionGenomeGene

Abstract

fetched live from OpenAlex

Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics that propagates millions of independent small viral subpopulations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction, an atypical case in evolution. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs between molecular traits of viral proteins shape viral evolution.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.005
GPT teacher head0.254
Teacher spread0.249 · 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 designSimulation or modeling
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

Citations71
Published2018
Admission routes1
Has abstractyes

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