1887

Abstract

Outbreaks of virulent and/or drug-resistant bacteria have a significant impact on human health and major economic consequences. Genomic islands (GIs; defined as clusters of genes of probable horizontal origin) are of high interest because they disproportionately encode virulence factors, some antimicrobial-resistance (AMR) genes, and other adaptations of medical or environmental interest. While microbial genome sequencing has become rapid and inexpensive, current computational methods for GI analysis are not amenable for rapid, accurate, user-friendly and scalable comparative analysis of sets of related genomes. To help fill this gap, we have developed IslandCompare, an open-source computational pipeline for GI prediction and comparison across several to hundreds of bacterial genomes. A dynamic and interactive visualization strategy displays a bacterial core-genome phylogeny, with bacterial genomes linearly displayed at the phylogenetic tree leaves. Genomes are overlaid with GI predictions and AMR determinants from the Comprehensive Antibiotic Resistance Database (CARD), and regions of similarity between the genomes are also displayed. GI predictions are performed using Sigi-HMM and IslandPath-DIMOB, the two most precise GI prediction tools based on nucleotide composition biases, as well as a novel -based consistency step to improve cross-genome prediction consistency. GIs across genomes sharing sequence similarity are grouped into clusters, further aiding comparative analysis and visualization of acquisition and loss of mobile GIs in specific sub-clades. IslandCompare is an open-source software that is containerized for local use, plus available via a user-friendly, web-based interface to allow direct use by bioinformaticians, biologists and clinicians (at https://islandcompare.ca).

Funding
This study was supported by the:
  • Canadian Institutes of Health Research
    • Principle Award Recipient: AndrewG McArthur
  • Genome Canada
    • Principle Award Recipient: AndrewG McArthur
  • David Braley Chair in Computational Biology
    • Principle Award Recipient: AndrewG McArthur
  • Cisco Research Chair in Bioinformatics
    • Principle Award Recipient: AndrewG McArthur
  • Simon Fraser University (Award SFU Big Data Graduate Scholarship)
    • Principle Award Recipient: KristenLeanne Gray
  • Omics and Data Science Initiative, Simon Fraser University (Award Omics Data Science Initiative Graduate Scholarship)
    • Principle Award Recipient: KristenLeanne Gray
  • Simon Fraser University (Award Weyerhaeuser Graduate Scholarship)
    • Principle Award Recipient: KristenLeanne Gray
  • Natural Sciences and Engineering Research Council of Canada (Award UBC/SFU NSERC-CREATE Bioinformatics Scholarship)
    • Principle Award Recipient: KristenLeanne Gray
  • Canadian Institutes of Health Research (Award Frederick Banting and Charles Best Canada Graduate Scholarship)
    • Principle Award Recipient: KristenLeanne Gray
  • Société Académique Vaudoise
    • Principle Award Recipient: ClaireBertelli
  • Swiss National Science Foundation (Award P300-PA_164673)
    • Principle Award Recipient: ClaireBertelli
  • Genome Canada
    • Principle Award Recipient: FionaSL Brinkman
  • Canadian Institutes of Health Research
    • Principle Award Recipient: FionaSL Brinkman
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-05-18
2024-04-25
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References

  1. Langille MGI, Laird MR, Hsiao WWL, Chiu TA, Eisen JA et al. MicrobeDB: a locally maintainable database of microbial genomic sequences. Bioinformatics 2012; 28:1947–1948 [View Article] [PubMed]
    [Google Scholar]
  2. Freschi L, Bertelli C, Jeukens J, Moore MP, Kukavica-Ibrulj I et al. Genomic characterisation of an international Pseudomonas aeruginosa reference panel indicates that the two major groups draw upon distinct mobile gene pools. FEMS Microbiol Lett 2018; 365:fny120 [View Article] [PubMed]
    [Google Scholar]
  3. Hingston P, Chen J, Dhillon BK, Laing C, Bertelli C et al. Genotypes associated with Listeria monocytogenes isolates displaying impaired or enhanced tolerances to cold, salt, acid, or desiccation stress. Front Microbiol 2017; 8:369 [View Article] [PubMed]
    [Google Scholar]
  4. Winsor GL, Griffiths EJ, Lo R, Dhillon BK, Shay JA et al. Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database. Nucleic Acids Res 2016; 44:D646–D653 [View Article] [PubMed]
    [Google Scholar]
  5. Dobrindt U, Hochhut B, Hentschel U, Hacker J. Genomic islands in pathogenic and environmental microorganisms. Nat Rev Microbiol 2004; 2:414–424 [View Article] [PubMed]
    [Google Scholar]
  6. Aminov RI. Horizontal gene exchange in environmental microbiota. Front Microbiol 2011; 2:158 [View Article] [PubMed]
    [Google Scholar]
  7. Ho Sui SJ, Fedynak A, Hsiao WWL, Langille MGI, Brinkman FSL. The association of virulence factors with genomic islands. PLoS One 2009; 4:e8094 [View Article] [PubMed]
    [Google Scholar]
  8. Hall RM. Salmonella genomic islands and antibiotic resistance in Salmonella enterica. Future Microbiol 2010; 5:1525–1538 [View Article] [PubMed]
    [Google Scholar]
  9. Gilmore MS, Lebreton F, van Schaik W. Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era. Curr Opin Microbiol 2013; 16:10–16 [View Article] [PubMed]
    [Google Scholar]
  10. Ingle DJ, Tauschek M, Edwards DJ, Hocking DM, Pickard DJ et al. Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants. Nat Microbiol 2016; 1:15010 [View Article] [PubMed]
    [Google Scholar]
  11. Winstanley C, Langille MGI, Fothergill JL, Kukavica-Ibrulj I, Paradis-Bleau C et al. Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. Genome Res 2009; 19:12–23 [View Article] [PubMed]
    [Google Scholar]
  12. Ladner JT, Grubaugh ND, Pybus OG, Andersen KG. Precision epidemiology for infectious disease control. Nat Med 2019; 25:206–211 [View Article] [PubMed]
    [Google Scholar]
  13. Gardy JL, Loman NJ. Towards a genomics-informed, real-time, global pathogen surveillance system. Nat Rev Genet 2018; 19:9–20 [View Article] [PubMed]
    [Google Scholar]
  14. Bertelli C, Greub G. Rapid bacterial genome sequencing: methods and applications in clinical microbiology. Clin Microbiol Infect 2013; 19:803–813 [View Article] [PubMed]
    [Google Scholar]
  15. Langille MGI, Hsiao WWL, Brinkman FSL. Detecting genomic islands using bioinformatics approaches. Nat Rev Microbiol 2010; 8:373–382 [View Article] [PubMed]
    [Google Scholar]
  16. Bertelli C, Tilley KE, Brinkman FSL. Microbial genomic island discovery, visualization and analysis. Brief Bioinform 2019; 20:1685–1698 [View Article] [PubMed]
    [Google Scholar]
  17. Langille MGI, Brinkman FSL. IslandViewer: an integrated interface for computational identification and visualization of genomic islands. Bioinformatics 2009; 25:664–665 [View Article] [PubMed]
    [Google Scholar]
  18. Dhillon BK, Chiu TA, Laird MR, Langille MGI, Brinkman FSL. IslandViewer update: improved genomic island discovery and visualization. Nucleic Acids Res 2013; 41:W129–W132 [View Article] [PubMed]
    [Google Scholar]
  19. Bertelli C, Laird MR, Williams KP. Simon Fraser University Research Computing Group Lau BY et al. IslandViewer 4: expanded prediction of genomic islands for larger-scale datasets. Nucleic Acids Res 2017; 45:W30–W35 [View Article] [PubMed]
    [Google Scholar]
  20. Afgan E, Baker D, Batut B, van den Beek M, Bouvier D et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res 2018; 46:W537–W544 [View Article] [PubMed]
    [Google Scholar]
  21. Cock PJA, Antao T, Chang JT, Chapman BA, Cox CJ et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 2009; 25:1422–1423 [View Article] [PubMed]
    [Google Scholar]
  22. Woods N, Brinkman FSL. Brinkman galaxy tools; 2019 https://zenodo.org/record/3364789
  23. Woods N. Brinkmanlab/biopython-convert: update biopython to v1.79; 2021 https://zenodo.org/record/5502644#.YnJWTtrMJPY
  24. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25:3389–3402 [View Article] [PubMed]
    [Google Scholar]
  25. Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J et al. BLAST+: architecture and applications. BMC Bioinformatics 2009; 10:421 [View Article] [PubMed]
    [Google Scholar]
  26. Cock PJA, Chilton JM, Grüning B, Johnson JE, Soranzo N. NCBI BLAST+ integrated into Galaxy. Gigascience 2015; 4:39 [View Article] [PubMed]
    [Google Scholar]
  27. Woods N. Brinkmanlab/feature_merge: ignore strand option; 2020 https://doi.org/10.5281/ZENODO.3364784
  28. Bertelli C, Brinkman FSL. Improved genomic island predictions with IslandPath-DIMOB. Bioinformatics 2018; 34:2161–2167 [View Article] [PubMed]
    [Google Scholar]
  29. Waack S, Keller O, Asper R, Brodag T, Damm C et al. Score-based prediction of genomic islands in prokaryotic genomes using hidden Markov models. BMC Bioinformatics 2006; 7:142 [View Article] [PubMed]
    [Google Scholar]
  30. Ondov BD, Treangen TJ, Melsted P, Mallonee AB, Bergman NH et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol 2016; 17:132 [View Article] [PubMed]
    [Google Scholar]
  31. Enright AJ, Van Dongen SA, Ouzounis CA. An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 2002; 30:1575–1584 [View Article] [PubMed]
    [Google Scholar]
  32. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014; 15:524 [View Article] [PubMed]
    [Google Scholar]
  33. Darling AE, Mau B, Perna NT. progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 2010; 5:e11147 [View Article] [PubMed]
    [Google Scholar]
  34. Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M et al. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res 2020; 48:D517–D525 [View Article] [PubMed]
    [Google Scholar]
  35. Jia B, Raphenya AR, Alcock B, Waglechner N, Guo P et al. CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res 2017; 45:D566–D573 [View Article] [PubMed]
    [Google Scholar]
  36. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990; 215:403–410 [View Article] [PubMed]
    [Google Scholar]
  37. Gouliouris T, Raven KE, Ludden C, Blane B, Corander J et al. Genomic surveillance of Enterococcus faecium reveals limited sharing of strains and resistance genes between livestock and humans in the United Kingdom. mBio 2018; 9:e01780-18 [View Article] [PubMed]
    [Google Scholar]
  38. Zaheer R, Cook SR, Barbieri R, Goji N, Cameron A et al. Surveillance of Enterococcus spp. reveals distinct species and antimicrobial resistance diversity across a one-health continuum. Sci Rep 2020; 10:3937 [View Article] [PubMed]
    [Google Scholar]
  39. Beutlich J, Jahn S, Malorny B, Hauser E, Hühn S et al. Antimicrobial resistance and virulence determinants in European Salmonella genomic island 1-positive Salmonella enterica isolates from different origins. Appl Environ Microbiol 2011; 77:5655–5664 [View Article] [PubMed]
    [Google Scholar]
  40. Mukhopadhyay AK, Chakraborty S, Takeda Y, Nair GB, Berg DE. Characterization of VPI pathogenicity island and CTXphi prophage in environmental strains of Vibrio cholerae. J Bacteriol 2001; 183:4737–4746 [View Article] [PubMed]
    [Google Scholar]
  41. Williams KP. Integration sites for genetic elements in prokaryotic tRNA and tmRNA genes: sublocation preference of integrase subfamilies. Nucleic Acids Res 2002; 30:866–875 [View Article] [PubMed]
    [Google Scholar]
  42. Reiter W-D, Palm P, Yeats S. Transfer RNA genes frequently serve as integration sites for prokaryotic genetic elements. Nucleic Acids Res 1989; 17:1907–1914 [View Article] [PubMed]
    [Google Scholar]
  43. Pavlovic G, Burrus V, Gintz B, Decaris B, Guédon G. Evolution of genomic islands by deletion and tandem accretion by site-specific recombination: ICESt1-related elements from Streptococcus thermophilus. Microbiology 2004; 150:759–774 [View Article] [PubMed]
    [Google Scholar]
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