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MPL resolves genetic linkage in fitness inference from complex evolutionary histories
- Source :
- Nature biotechnology, vol 39, iss 4, Nat Biotechnol
- Publication Year :
- 2021
- Publisher :
- eScholarship, University of California, 2021.
-
Abstract
- Genetic linkage causes the fate of new mutations in a population to be contingent on the genetic background on which they appear. This makes it challenging to identify how individual mutations affect fitness. To overcome this challenge, we developed marginal path likelihood (MPL), a method to infer selection from evolutionary histories that resolves genetic linkage. Validation on real and simulated data sets shows that MPL is fast and accurate, outperforming existing inference approaches. We found that resolving linkage is crucial for accurately quantifying selection in complex evolving populations, which we demonstrate through a quantitative analysis of intrahost HIV-1 evolution using multiple patient data sets. Linkage effects generated by variants that sweep rapidly through the population are particularly strong, extending far across the genome. Taken together, our results argue for the importance of resolving linkage in studies of natural selection.
- Subjects :
- Computer science
Evolution
Genetic Linkage
Population
Biomedical Engineering
Inference
Bioengineering
HIV Infections
Computational biology
Applied Microbiology and Biotechnology
Genome
Article
Evolution, Molecular
03 medical and health sciences
0302 clinical medicine
Genetic
Genetic linkage
Models
Receptors
Genetics
Humans
Selection, Genetic
education
Selection
Selection (genetic algorithm)
030304 developmental biology
Linkage (software)
0303 health sciences
education.field_of_study
Likelihood Functions
Natural selection
Models, Genetic
Human Genome
Computational Biology
Molecular
Thrombopoietin
Mutation (genetic algorithm)
Mutation
HIV-1
Molecular Medicine
Generic health relevance
Receptors, Thrombopoietin
030217 neurology & neurosurgery
Algorithms
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Nature biotechnology, vol 39, iss 4, Nat Biotechnol
- Accession number :
- edsair.doi.dedup.....667b7f2cd41b9f5c7f2137c1a8f80a53