Imperial College London
Alternate

Professor Francis Drobniewski

Faculty of Medicine, Department of Infectious Disease

Chair in Global Health and Tuberculosis
 
 
 
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Contact

 

f.drobniewski

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilson:2020:molbev/msaa069,
author = {Wilson, DJ and Crook, DW and Peto, TEA and Walker, AS and Hoosdally, SJ and Gibertoni, Cruz AL and Carter, J and Grazian, C and Earle, SG and Kouchaki, S and Lachapelle, A and Yang, Y and Clifton, DA and Fowler, PW and Iqbal, Z and Hunt, M and Knaggs, J and Smith, EG and Rathod, P and Jarrett, L and Matias, D and Cirillo, DM and Borroni, E and Battaglia, S and Ghodousi, A and Spitaleri, A and Cabibbe, A and Tahseen, S and Nilgiriwala, K and Shah, S and Rodrigues, C and Kambli, P and Surve, U and Khot, R and Niemann, S and Kohl, TA and Merker, M and Hoffmann, H and Todt, K and Plesnik, S and Ismail, N and Omar, SV and Joseph, L and Thwaites, G and Thuong, TNT and Ngoc, NH and Srinivasan, V and Walker, TM and Moore, D and Coronel, J and Solano, W and Gao, GF and He, G and Zhao, Y and Liu, C and Ma, A and Zhu, B and Laurenson, I and Claxton, P and Koch, A and Wilkinson, R and Lalvani, A and Posey, J and Gardy, J and Werngren, J and Paton, N and Jou, R and Wu, M-H and Lin, W-H and Ferrazol},
doi = {molbev/msaa069},
journal = {Molecular Biology and Evolution},
pages = {2450--2460},
title = {GenomegaMap: within-species genome-wide dN/dS estimation from over 10,000 genomes},
url = {http://dx.doi.org/10.1093/molbev/msaa069},
volume = {37},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap’s simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species.
AU  - Wilson,DJ
AU  - Crook,DW
AU  - Peto,TEA
AU  - Walker,AS
AU  - Hoosdally,SJ
AU  - Gibertoni,Cruz AL
AU  - Carter,J
AU  - Grazian,C
AU  - Earle,SG
AU  - Kouchaki,S
AU  - Lachapelle,A
AU  - Yang,Y
AU  - Clifton,DA
AU  - Fowler,PW
AU  - Iqbal,Z
AU  - Hunt,M
AU  - Knaggs,J
AU  - Smith,EG
AU  - Rathod,P
AU  - Jarrett,L
AU  - Matias,D
AU  - Cirillo,DM
AU  - Borroni,E
AU  - Battaglia,S
AU  - Ghodousi,A
AU  - Spitaleri,A
AU  - Cabibbe,A
AU  - Tahseen,S
AU  - Nilgiriwala,K
AU  - Shah,S
AU  - Rodrigues,C
AU  - Kambli,P
AU  - Surve,U
AU  - Khot,R
AU  - Niemann,S
AU  - Kohl,TA
AU  - Merker,M
AU  - Hoffmann,H
AU  - Todt,K
AU  - Plesnik,S
AU  - Ismail,N
AU  - Omar,SV
AU  - Joseph,L
AU  - Thwaites,G
AU  - Thuong,TNT
AU  - Ngoc,NH
AU  - Srinivasan,V
AU  - Walker,TM
AU  - Moore,D
AU  - Coronel,J
AU  - Solano,W
AU  - Gao,GF
AU  - He,G
AU  - Zhao,Y
AU  - Liu,C
AU  - Ma,A
AU  - Zhu,B
AU  - Laurenson,I
AU  - Claxton,P
AU  - Koch,A
AU  - Wilkinson,R
AU  - Lalvani,A
AU  - Posey,J
AU  - Gardy,J
AU  - Werngren,J
AU  - Paton,N
AU  - Jou,R
AU  - Wu,M-H
AU  - Lin,W-H
AU  - Ferrazoli,L
AU  - de,Oliveira RS
AU  - Arandjelovic,I
AU  - Chaiprasert,A
AU  - Comas,I
AU  - Roig,CJ
AU  - Drobniewski,FA
AU  - Farhat,MR
AU  - Gao,Q
AU  - Hee,ROT
AU  - Sintchenko,V
AU  - Supply,P
AU  - van,Soolingen D
DO  - molbev/msaa069
EP  - 2460
PY  - 2020///
SN  - 0737-4038
SP  - 2450
TI  - GenomegaMap: within-species genome-wide dN/dS estimation from over 10,000 genomes
T2  - Molecular Biology and Evolution
UR  - http://dx.doi.org/10.1093/molbev/msaa069
UR  - https://academic.oup.com/mbe/article/37/8/2450/5804989
UR  - http://hdl.handle.net/10044/1/82880
VL  - 37
ER  -
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