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A phylogeny-based sampling strategy and power calculator informs genome-wide associations study design for microbial pathogens

Title: A phylogeny-based sampling strategy and power calculator informs genome-wide associations study design for microbial pathogens
Authors: Farhat, MR
Shapiro, BJ
Sheppard, SK
Colijn, C
Murray, M
Item Type: Journal Article
Abstract: Whole genome sequencing is increasingly used to study phenotypic variation among infectious pathogens and to evaluate their relative transmissibility, virulence, and immunogenicity. To date, relatively little has been published on how and how many pathogen strains should be selected for studies associating phenotype and genotype. There are specific challenges when identifying genetic associations in bacteria which often comprise highly structured populations. Here we consider general methodological questions related to sampling and analysis focusing on clonal to moderately recombining pathogens. We propose that a matched sampling scheme constitutes an efficient study design, and provide a power calculator based on phylogenetic convergence. We demonstrate this approach by applying it to genomic datasets for two microbial pathogens: Mycobacterium tuberculosis and Campylobacter species.
Issue Date: 15-Nov-2014
Date of Acceptance: 30-Oct-2014
URI: http://hdl.handle.net/10044/1/49763
DOI: https://dx.doi.org/10.1186/s13073-014-0101-7
ISSN: 1756-994X
Publisher: BioMed Central
Journal / Book Title: Genome Medicine
Volume: 6
Issue: 11
Copyright Statement: © 2014 Farhat et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/I031626/1
EP/K026003/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
DRUG-RESISTANT TUBERCULOSIS
MYCOBACTERIUM-TUBERCULOSIS
PRINCIPAL-COMPONENTS
BACTERIAL GENOMES
RECOMBINATION
INFERENCE
SELECTION
MODEL
EVOLUTION
STRATIFICATION
0604 Genetics
1103 Clinical Sciences
Publication Status: Published
Article Number: ARTN 101
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences



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