Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Feb 17:3:e761.
doi: 10.7717/peerj.761. eCollection 2015.

Concordance and discordance of sequence survey methods for molecular epidemiology

Eduardo Castro-Nallar  1 , Nur A Hasan  2 , Thomas A Cebula  3 , Rita R Colwell  4 , Richard A Robison  5 , W Evan Johnson  6 , Keith A Crandall  1
Affiliations

Concordance and discordance of sequence survey methods for molecular epidemiology

Eduardo Castro-Nallar et al. PeerJ. .

Abstract

The post-genomic era is characterized by the direct acquisition and analysis of genomic data with many applications, including the enhancement of the understanding of microbial epidemiology and pathology. However, there are a number of molecular approaches to survey pathogen diversity, and the impact of these different approaches on parameter estimation and inference are not entirely clear. We sequenced whole genomes of bacterial pathogens, Burkholderia pseudomallei, Yersinia pestis, and Brucella spp. (60 new genomes), and combined them with 55 genomes from GenBank to address how different molecular survey approaches (whole genomes, SNPs, and MLST) impact downstream inferences on molecular evolutionary parameters, evolutionary relationships, and trait character associations. We selected isolates for sequencing to represent temporal, geographic origin, and host range variability. We found that substitution rate estimates vary widely among approaches, and that SNP and genomic datasets yielded different but strongly supported phylogenies. MLST yielded poorly supported phylogenies, especially in our low diversity dataset, i.e., Y. pestis. Trait associations showed that B. pseudomallei and Y. pestis phylogenies are significantly associated with geography, irrespective of the molecular survey approach used, while Brucella spp. phylogeny appears to be strongly associated with geography and host origin. We contrast inferences made among monomorphic (clonal) and non-monomorphic bacteria, and between intra- and inter-specific datasets. We also discuss our results in light of underlying assumptions of different approaches.

Keywords: Biological weapons; Bioterrorism; Data type; Genomes; High-throughput sequencing; MLST; Molecular epidemiology; Phylogenomics; Phylogeography; SNP.

PubMed Disclaimer

Conflict of interest statement

Eduardo Castro-Nallar, W. Evan Johnson, and Keith A. Crandall have a combination of ownership of, and employment in, Aperiomics, Inc. Nur A. Hassan, Thomas A. Cebula, and Rita R. Colwell have a combination of ownership of, and employment in, CosmosID.

Figures

Figure 1
Figure 1. Substitution rates for all datasets as estimated from different molecular survey approaches.
Genome/SNP chr I/II refers to estimates from different chromosomes. Burkholderia pseudomallei (A), Brucella spp. (B), and Yersinia pestis (C). Note different scale for species rates.
Figure 2
Figure 2. Median node ages in years.
Burkholderia pseudomallei (A), Brucella spp. (B), and Yersinia pestis (C) median estimates and their 95% highest posterior density (HPD) interval according to molecular survey approach (only chromosome I showed; see Fig. S1). Nodes are numbered from youngest to oldest.
Figure 3
Figure 3. Burkholderia pseudomallei phylogenies by survey approach.
MLST phylogeny (A) is less resolved and poorly supported compared to SNP (B) and genome (C) phylogenies (only chromosome I showed).
See this image and copyright information in PMC

References

    1. Achtman M. Evolution, population structure, and phylogeography of genetically monomorphic bacterial pathogens. Annual Review of Microbiology. 2008;62:53–70. doi: 10.1146/annurev.micro.62.081307.162832. - DOI - PubMed
    1. Achtman M, Zurth K, Morelli G, Torrea G, Guiyoule A, Carniel E. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proceedings of the National Academy of Sciences of the United States of America. 1999;96:14043–14048. doi: 10.1073/pnas.96.24.14043. - DOI - PMC - PubMed
    1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. Journal of Molecular Biology. 1990;215:403–410. doi: 10.1016/S0022-2836(05)80360-2. - DOI - PubMed
    1. Ayres DL, Darling A, Zwickl DJ, Beerli P, Holder MT, Lewis PO, Huelsenbeck JP, Ronquist F, Swofford DL, Cummings MP. BEAGLE: an application programming interface and high-performance computing library for statistical phylogenetics. Systematic Biology. 2012;61:170–173. doi: 10.1093/sysbio/syr100. - DOI - PMC - PubMed
    1. Baker S, Hanage WP, Holt KE. Navigating the future of bacterial molecular epidemiology. Current Opinion in Microbiology. 2010;13:640–645. doi: 10.1016/j.mib.2010.08.002. - DOI - PMC - PubMed

LinkOut - more resources