Genome-wide epistasis and co-selection study using mutual information.

Nucleic Acids Research
Johan PensarJukka Corander

Abstract

Covariance-based discovery of polymorphisms under co-selective pressure or epistasis has received considerable recent attention in population genomics. Both statistical modeling of the population level covariation of alleles across the chromosome and model-free testing of dependencies between pairs of polymorphisms have been shown to successfully uncover patterns of selection in bacterial populations. Here we introduce a model-free method, SpydrPick, whose computational efficiency enables analysis at the scale of pan-genomes of many bacteria. SpydrPick incorporates an efficient correction for population structure, which adjusts for the phylogenetic signal in the data without requiring an explicit phylogenetic tree. We also introduce a new type of visualization of the results similar to the Manhattan plots used in genome-wide association studies, which enables rapid exploration of the identified signals of co-evolution. Simulations demonstrate the usefulness of our method and give some insight to when this type of analysis is most likely to be successful. Application of the method to large population genomic datasets of two major human pathogens, Streptococcus pneumoniae and Neisseria meningitidis, revealed both previously ident...Continue Reading

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Citations

Oct 15, 2019·Microbial Genomics·Tamsin C M DewéNicholas J Croucher
Jul 24, 2020·Genome Biology·Gerry Tonkin-HillJulian Parkhill
Mar 21, 2020·ELife·Yujun CuiDaniel Falush
Feb 27, 2020·Microbial Genomics·Fiona Jane WhelanJames Oscar McInerney
Aug 28, 2020·Frontiers in Microbiology·Rebecca J HallMaria Rosa Domingo-Sananes
Jun 25, 2020·Physical Review. E·Hong-Li Zeng, Erik Aurell
May 9, 2021·Molecular Biology and Evolution·Fiona J WhelanJames O McInerney
Oct 19, 2021·Molecular Biology and Evolution·Claire ChewapreechaJukka Corander
Nov 14, 2021·Nature Reviews. Microbiology·Brian J ArnoldWilliam P Hanage

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Software Mentioned

GWES
SuperDCA
ARACNE
DCA
fwdpp
SpydrPick
FastTree
SpyderPick
Alignment Manipulation and Summary ( AMAS )
SNAP2

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