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

Genome medicine (2014-12-09)
Maha R Farhat, B Jesse Shapiro, Samuel K Sheppard, Caroline Colijn, Megan Murray
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.

MATERIALS
Product Number
Brand
Product Description

Calcium pantothenate, European Pharmacopoeia (EP) Reference Standard
USP
Calcium Pantothenate, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
D-Pantothenic acid hemicalcium salt, ≥98.0%
Sigma-Aldrich
D-Pantothenic acid hemicalcium salt, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
Calcium pantothenate, meets USP testing specifications, monograph mol wt. 476.53 (C18H32CaN2O10)