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Record W3146031059 · doi:10.1101/2021.03.30.437711

Taming strong selection with large sample sizes

2021· preprint· en· W3146031059 on OpenAlexaff
Ivan Krukov, Simon Gravel

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEvolution and Genetic Dynamics
Canadian institutionsMcGill UniversityMcGill Genome Centre
Fundersnot available
KeywordsCoalescent theorySelection (genetic algorithm)Genetic driftNatural selectionSample size determinationDirectional selectionStatistical physicsPopulationAllele frequencySample (material)Neutral theory of molecular evolutionLimit (mathematics)MathematicsStatisticsAlleleBiologyPhysicsGenetic variationComputer scienceGeneticsMathematical analysisGene

Abstract

fetched live from OpenAlex

1 Abstract The fate of mutations and the genetic load of populations depend on the relative importance of genetic drift and natural selection. In addition, the accuracy of numerical models of evolution depends on the strength of both selection and drift: strong selection breaks the assumptions of the nearly neutral model, and drift coupled with large sample sizes breaks Kingman’s coalescent model. Thus, the regime with strong selection and large sample sizes, relevant to the study of pathogenic variation, appears particularly daunting. Surprisingly, we find that the interplay of drift and selection in that regime can be used to define asymptotically closed recursions for the distribution of allele frequencies that are accurate well beyond the strong selection limit. Selection becomes more analytically tractable when the sample size n is larger than twice the population-scaled selection coefficient: n ≥ 2 Ns (4 Ns in diploids). That is, when the expected number of coalescent events in the sample is larger than the number of selective events. We construct the relevant transition matrices, show how they can be used to accurately compute distributions of allele frequencies, and show that the distribution of deleterious allele frequencies is sensitive to details of the evolutionary model.

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)0.024
metaresearch head score (Gemma)0.125
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: none
Teacher disagreement score0.024
Threshold uncertainty score0.128

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0240.125
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.005
Scholarly communication0.0020.004
Open science0.0020.004
Research integrity0.0010.003
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 head0.007
GPT teacher head0.213
Teacher spread0.206 · 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

Citations3
Published2021
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicEvolution and Genetic DynamicsFrench-language works237,207