Mge-cluster: a reference-free approach for typing bacterial plasmids

Author:

Arredondo-Alonso Sergio12ORCID,Gladstone Rebecca A1,Pöntinen Anna K13,Gama João A4,Schürch Anita C5ORCID,Lanza Val F67,Johnsen Pål Jarle4,Samuelsen Ørjan34ORCID,Tonkin-Hill Gerry12ORCID,Corander Jukka128

Affiliation:

1. Department of Biostatistics, University of Oslo , Oslo , Norway

2. Parasites and Microbes, Wellcome Sanger Institute , Cambridge , UK

3. Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway , Tromsø, Norway

4. Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway , Tromsø, Norway

5. Department of Medical Microbiology , UMC Utrecht, Utrecht , The Netherlands

6. CIBERINFEC , Madrid , Spain

7. Bioinformatics Unit, University Hospital Ramón y Cajal , IRYCIS, Madrid , Spain

8. Department of Mathematics and Statistics, Helsinki Institute of Information Technology (HIIT), FI-00014 University of Helsinki , Helsinki , Finland

Abstract

Abstract Extrachromosomal elements of bacterial cells such as plasmids are notorious for their importance in evolution and adaptation to changing ecology. However, high-resolution population-wide analysis of plasmids has only become accessible recently with the advent of scalable long-read sequencing technology. Current typing methods for the classification of plasmids remain limited in their scope which motivated us to develop a computationally efficient approach to simultaneously recognize novel types and classify plasmids into previously identified groups. Here, we introduce mge-cluster that can easily handle thousands of input sequences which are compressed using a unitig representation in a de Bruijn graph. Our approach offers a faster runtime than existing algorithms, with moderate memory usage, and enables an intuitive visualization, classification and clustering scheme that users can explore interactively within a single framework. Mge-cluster platform for plasmid analysis can be easily distributed and replicated, enabling a consistent labelling of plasmids across past, present, and future sequence collections. We underscore the advantages of our approach by analysing a population-wide plasmid data set obtained from the opportunistic pathogen Escherichia coli, studying the prevalence of the colistin resistance gene mcr-1.1 within the plasmid population, and describing an instance of resistance plasmid transmission within a hospital environment.

Funder

Marie Skłodowska-Curie Actions

Trond Mohn Foundation

European Research Council

ZonMW

Publisher

Oxford University Press (OUP)

Subject

Applied Mathematics,Computer Science Applications,Genetics,Molecular Biology,Structural Biology

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