title: Defining the estimated core genome of bacterial populations using a Bayesian decision model.
abstract: The bacterial core genome is of intense interest and the volume of whole genome sequence data in the public domain available to investigate it has increased dramatically. The aim of our study was to develop a model to estimate the bacterial core genome from next-generation whole genome sequencing data and use this model to identify novel genes associated with important biological functions. Five bacterial datasets were analysed, comprising 2096 genomes in total. We developed a Bayesian decision model to estimate the number of core genes, calculated pairwise evolutionary distances (p-distances) based on nucleotide sequence diversity, and plotted the median p-distance for each core gene relative to its genome location. We designed visually-informative genome diagrams to depict areas of interest in genomes. Case studies demonstrated how the model could identify areas for further study, e.g. 25% of the core genes with higher sequence diversity in the Campylobacter jejuni and Neisseria meningitidis genomes encoded hypothetical proteins. The core gene with the highest p-distance value in C. jejuni was annotated in the reference genome as a putative hydrolase, but further work revealed that it shared sequence homology with beta-lactamase/metallo-beta-lactamases (enzymes that provide resistance to a range of broad-spectrum antibiotics) and thioredoxin reductase genes (which reduce oxidative stress and are essential for DNA replication) in other C. jejuni genomes. Our Bayesian model of estimating the core genome is principled, easy to use and can be applied to large genome datasets. This study also highlighted the lack of knowledge currently available for many core genes in bacterial genomes of significant global public health importance.
authors.affiliation: Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: van Tonder
authors.affiliation: Mathematical Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Shilan
authors.initials: S
authors.lastname: Mistry
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Bray
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Dorothea M C
authors.initials: DM
authors.lastname: Hill
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Cody
authors.affiliation: Mathematical Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Chris L
authors.initials: CL
authors.lastname: Farmer
authors.affiliation: Hubert Department of Global Health Epidemiology, Rollins School of Public Health, Atlanta, Georgia, United States of America.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
authors.affiliation: Pathogen Genomics Team, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Pathogen Genomics Team, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Brueggemann
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D001499:Bayes Theorem; D016123:Campylobacter jejuni / Q000235:genetics; D030541:Databases, Genetic; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics; D008957:Models, Genetic; D009345:Neisseria meningitidis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins